Antimicrobial Guide: Empiric Therapy & Treatment Recommendations For Adult Patients by uri703

2019-2020 Antimicrobial Guide

Empiric Therapy & Treatment Recommendations For Adult Patients

Table of Contents A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 B. Guidelines for the Treatment of Various Infections in Adults Central Nervous System (CNS) • Meningitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Clostridium difficile Infection (CDI) . . . . . . . . . . . . . . . . . . . . . . . . . 4 Extended Spectrum Beta-Lactamases Infections (ESBL). . . . . . . . . . . . 6 Febrile Neutropenia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Fungal Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Influenza. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Intra-abdominal Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Lyme Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Proton Pump Inhibitor (PPI) Use. . . . . . . . . . . . . . . . . . . . . . . . . . 14 Procalcitonin Biomarker Use . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Respiratory Tract - Upper and Lower • Acute Bacterial Sinusitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 • Acute Pharyngitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 • Chronic Obstructive Pulmonary Disease (COPD) Exacerbation. . . . . 18 • Rapid Respiratory Pathogen Panel (BioFire) Use . . . . . . . . . . . . . . 19 Sepsis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Sexually Transmitted Infections (STI). . . . . . . . . . . . . . . . . . . . . . . 21 Skin and Soft Tissue • Skin and Soft Tissue Infections (SSTI) . . . . . . . . . . . . . . . . . . . . . 25 • Diabetic Foot Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Surgical Decolonization and Prophylaxis. . . . . . . . . . . . . . . . . . . . 29 Urinary Tract • Catheter-Associated Urinary Tract Infection (CA-UTI). . . . . . . . . . . 32 • Non-Catheter Associated Urinary Tract Infection/Cystitis. . . . . . . . 33 • Prostatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 C. Immunizations • Pneumococcal Vaccine. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 D. Antibiogram. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 E.

Guidelines for Restricted Antimicrobials. . . . . . . . . . . . . . . . . . . 41 Antibiotics • Ceftaroline (Teflaro®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 • Ceftazidime/avibactam (Avycaz®) . . . . . . . . . . . . . . . . . . . . . . . 43

Table of Contents • Ceftolozane/tazobactam (Zerbaxa®) . . . . . . . . . . . . . . . . . . . . . 44 • Dalbavancin (Dalvance®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 • Daptomycin (Cubicin®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 • Delafloxacin (Baxdela®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 • Ertapenem (Invanz®) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48 • Fidaxomicin (Dificid®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 • Fosfomycin (Monurol®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 • Linezolid (Zyvox®) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 • Meropenem and Vaborbactam (Vabomere®). . . . . . . . . . . . . . . . 52 • Oritavancin (Orbactiv®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 • Polymyxin B. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 • Colistin (Polymyxin E). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 • Tedizolid (Sivextro®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 • Tigecycline (Tygacil®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 Antifungals • Amphotericin B lipid complex (Abelcet®) . . . . . . . . . . . . . . . . . . 58 • Caspofungin (Cancidas ®) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 • Isavuconazonium sulfate (Cresemba®) . . . . . . . . . . . . . . . . . . . . 60 • Voriconazole (VFend®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 Monoclonal Antibody • Bezlotoxumab (Zinplav®). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 F.

Vancomycin Dosing and Monitoring in Adult Patients . . . . . . . . . 63

G. Aminoglycoside High Dose Once Daily (HDOD) and Monitoring in Adult Patients. . . . . . . . . . . . . . . . . . . . . . . . 67 H. Antimicrobial Dosing Based on Renal Function . . . . . . . . . . . . . . 69 I.

Antimicrobial Duration of Therapy. . . . . . . . . . . . . . . . . . . . . . . 73

IV to PO Antibiotic Step-Down Guidelines. . . . . . . . . . . . . . . . . . 76

K. Infection Control • Twelve Steps to Prevent Antimicrobial Resistance. . . . . . . . . . . . . 77 • Contact Precautions for Infection Control . . . . . . . . . . . . . . . . . . 77 L.

Pharmacokinetic Equations/Calculations. . . . . . . . . . . . . . . . . . 78

â&#x20AC;&#x201A;Introduction Introduction Antimicrobial resistance is globally recognized as one of the greatest healthcare threats. Infections associated with multi-drug resistant organisms and limited antimicrobial choices have placed an immense burden upon clinicians. In order to preserve currently available antimicrobials we must use them appropriately; ensuring that each patient is on the right drug, route, dose, and duration and only used when needed. The pathways and tables in this booklet are based on national guidelines and consensus statements, expert opinions from the Infectious Diseases team (pharmacy and medicine) and microbiology data from the microbiology laboratory. DISCLAIMER: The opinions expressed in this publication reflect those of the authors to the best of their ability. However, the authors make no warranty regarding the contents of the publication. The guidelines described herein are general and may not apply to a specific patient. The recommendations given in this guide are meant to serve as treatment guidelines. They should not replace clinical judgment or Infectious Diseases consultation when indicated. The recommendations may not be appropriate at other settings. We have attempted to verify that all information is correct but because of ongoing research, recommendations may change. Please let us know if there are sections that you think could be improved or if there is more information you would like to see included. Our goal is for the Antimicrobial Stewardship Program to be a useful service in optimizing antibiotic use and patient outcomes. We welcome your thoughts and comments. Thank you, Kerry L. LaPlante, PharmD., FCCP, FIDSA Professor of Pharmacy, University of Rhode Island, Kingston, RI Adjunct Professor of Medicine, Brown University, Providence, RI Director of the Rhode Island Infectious Diseases Research Program (RIID) and Infectious Diseases Pharmacotherapy Specialist, Providence Veterans Medical Center, RI Kerry.LaPlante@va.gov or KerryLaPlante@uri.edu.

The following people reviewed ALL the treatment guidelines: Kerry L. LaPlante, PharmD, FCCP (Infectious Diseases) Melissa Gaitanis, MD (Chief of Infectious Diseases) Haley Appaneal, PharmD (Antibiotic Stewardship) The following people served as section/topic reviewers for this version: Tanya Ali, MD (Infectious Diseases), Emily Bodo, PharmD (Fellow), Patricia Cristofaro, MD (Infectious Diseases), Jaclyn Cusumano, PharmD (Fellow), Amanda Noska, MD (Infection Control), Stephanie Tolg, PharmD (Fellow), Maria Trice, BSN RN (Infection Control) Editorial and formatting assistance Jennifer DeAngelis, Graphic Design, Kathie McKinstry, Graphic Design,

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Central Nervous System: Meningitis Central Nervous System: Meningitis ACUTE BACTERIAL MENINGITIS Clinical Syndrome Age < 50 Most commonly isolated organisms: • S. pneumoniae • N. meningitidis • H . influenzae

Age ≥ 50 Most commonly isolated organisms: • S. pneumoniae • N. meningitidis • H. influenzae

• L. monocytogenes

• Aerobic gram negative bacilli

Preferred Regimen

Alternative Regimen

Ceftriaxone 2 gm IV Q12H AND Vancomycin 15 mg/kg IV AND Dexamethasone 0.15 mg/kg IV Q6H given 10 to 20 minutes before the first dose of antimicrobial therapy and continue for 4 days for pneumococcal meningitis (discontinue for all other microorganisms)

PCN allergy (anaphylaxis): Vancomycin 15 mg/kg IV AND Moxifloxacin 400 mg IV Q24H AND Dexamethasone 0.15 mg/kg IV Q6H given 10 to 20 minutes before the first dose of antimicrobial therapy and continue for 4 days for pneumococcal meningitis (discontinue for all other microorganisms)

Ceftriaxone 2 gm IV Q12H AND Vancomycin 15 mg/kg IV AND Ampicillin 2 gm IV Q4H AND Dexamethasone 0.15 mg/kg IV Q6H given 10 to 20 minutes before the first dose of antimicrobial therapy and continue for 4 days for pneumococcal meningitis (discontinue for all other microorganisms)

PCN allergy (anaphylaxis): Vancomycin IV 15 mg/kg AND Moxifloxacin 400 mg IV Q24H AND SMX/TMP 5 mg/kg IV Q6H AND Dexamethasone 0.15 mg/kg IV Q6H given 10 to 20 minutes before the first dose of antimicrobial therapy and continue for 4 days for pneumococcal meningitis (discontinue for all other microorganisms)

Diagnostics and Clinical Considerations • Consult Infectious Diseases • Obtain lumbar puncture and blood cultures prior to starting therapy • Consider proceeding to antibiotics directly if lumbar puncture is delayed for any reason • Patients with the following conditions should receive head CT prior to lumbar puncture: - Immunocompromised (HIV) - History of CNS lesion, stroke or focal infection - New onset seizure - Papilledema - Abnormal level of consciousness - Focal neurologic deficit • Typical CSF findings in bacterial meningitis - Cloudy CSF - Glucose < 40 mg/dL OR <50% serum - Protein 100-500 - WBC 1000-5000 - > 90% PMNs • Narrow therapy based on CSF culture results • If CSF culture negative, consult ID • Repeat lumbar puncture if no improvement in 48 hours and consider viral panel

CNS= central nervous system; CSF= cerebral spinal fluid; CT= computed tomography; H= hour(s); HIV= human immunodeficiency virus; ID= infectious diseases; IV= intravenous; PCN= Penicillin; PMNs= poly morphonuclear cells; Q= every; SMX/TMP= Sulfamethoxazole/Trimethoprim; WBC= white blood cell

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Central Nervous System: Meningitis

Central Nervous System: Meningitis HEALTH CARE -ASSOCIATED VENTRICULITIS AND MENINGITIS Central Nervous System: Meningitis Clinical Syndrome

Preferred Regimen

HEALTH CARE-ASSOCIATED VENTRICULITIS AND MENINGITIS

Empiric or targeted treatment Clinical Syndrome

Consult Infectious Diseases

Empiric or targeted treatment

Consult Infectious Diseases

Preferred Regimen

ASEPTIC/ VIRAL/OTHER MENINGITIS AND HERPES SIMPLEX TYPE 2 Diagnostics and Clinical Clinical Syndrome Preferred Regimen ASEPTIC/ VIRAL/OTHER MENINGITIS AND HERPES SIMPLEXConsiderations TYPE 2 Aseptic/Viral/Other Clinical Syndrome

• Respiratory viruses • Enteroviruses (90%) Aseptic/Viral/Other • Arboviruses •• Respiratory viruses West Nile Virus •• Enteroviruses (90%) Epstein Barr Virus •• Arboviruses Lyme •• West Nile Virus Syphilis • Epstein Barr Virus • Lyme • Syphilis

Supportive care Regimen Preferred

Diagnostics and Diseases Clinical • Consult Infectious Considerations

• Send CSF and order: - Viral culture Diseases • Consult Infectious - HSV PCR • Send and order: - CSF Enteroviral PCR If Lyme Suspected: -- Viral Lymeculture Antibody (IgG index, Ceftriaxone 2 gm IV Q24H - HSV PCR requires simultaneous - Enteroviral PCR serum) -- Lyme VDRL Antibody (IgG index, requires simultaneous • Typical CSF findings in viral serum) meningitis VDRL CSF -- Clear • Typical CSF findings viral - Glucose 30-70 in mg/dL meningitis - Protein 30-150 -- Clear CSF WBC 100-1000 Acyclovir 10 mg/kg* IV Q8H Herpes Simplex Type 2 -- Glucose 30-70increased mg/dL < 90% PMNs, Treat for 7 to 10 days - Protein 30-150 lymphocytes - WBC 100-1000 Acyclovir 10 mg/kg* IV Q8H Herpes Simplex Type 2 - < 90% PMNs, increased Treat for 7 to 10 days CSF= cerebral spinal fluid; H= hour(s); HSV= Herpes Simplex Virus; IV= intravenous; LP= lumbar puncture; PCR= Polymerase Chain lymphocytes Reaction; PMNs= poly morphonuclear cells; Q= every; VDRL= Veneral Disease Research Laboratory Test; WBC= white blood cell If Lyme Suspected: Supportive Ceftriaxonecare 2 gm IV Q24H

*CSF= Acyclovir mg/kg dosing on ideal body weight. cerebral spinal fluid;based H= hour(s); HSV= Herpes Simplex Virus; IV= intravenous; LP= lumbar puncture; PCR= Polymerase Chain Reaction; PMNs= poly morphonuclear cells; Q= every; VDRL= Veneral Disease Research Laboratory Test; WBC= white blood cell NOTE: If dexamethasone or imaging studies (LP or CT) is not immediately available DO NOT delay administration of *antibiotics. Acyclovir mg/kg dosing based on ideal body weight. NOTE: IfDosing based on normal renalstudies function. of Contentsavailable for section Vancomycin Dosing and Monitoring NOTE: dexamethasone or imaging (LP Refer or CT)to is Table not immediately DOonNOT delay administration of in Adult Patients and Antimicrobial Dosing for Adult Patients Based on Renal Function antibiotics. NOTE: Dosing based on normal renal function. Refer to Table of Contents for section on Vancomycin Dosing and Monitoring in Adult Patients and Antimicrobial Dosing for Adult Patients Based on Renal Function

References: 1. Tunkel AR, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004 Nov 1;39(9):1267-84. 2. Tunkel AR, et al. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis. Clin Infect Dis. 2017 Feb 14. References:

1. Tunkel AR, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004 Nov 1;39(9):1267-84. 2. Tunkel AR, et al. 2017 Infectious Diseases Society of America's Clinical Practice Guidelines for Healthcare-AssociatedPAGE 3 Ventriculitis and Meningitis. Clin Infect Dis. 2017 Feb 14.

Clostridium difficile Infection (CDI) Clostridium difficile Infection (CDI) • Discontinue therapy with the inciting antibiotic agent as soon as possible, especially broadspectrum antibiotics (fluoroquinolones, clindamycin, piperacillin-tazobactam, cephalosporins), as this may influence the risk of clinical response and CDI recurrence • Discontinue proton-pump inhibitors (PPIs) if unnecessary (see PPI pathway) • Discontinue use of any anti-diarrheal/antiperistaltic agents • Start antibiotic therapy for CDI empirically if a substantial delay in laboratory confirmation is expected (>48 h) or if a patient presents with fulminant CDI (see definition below) INITIAL EPISODE Clinical Classification Initial episode, non-severe

Severe

Fulminant (previously referred to as severe, complicated CDI)

Supportive Clinical Data •

Recommended Regimens

Unexplained and new-onset diarrhea (≥ 3 unformed stools in 24H) AND • WBC < 15,000 cells/mL AND • SCr < 1.5 mg/dL

Vancomycin 125 mg PO Q6H for 10 days OR Fidaxomicin 200 mg PO Q12H for 10 days

• Diarrhea AND • WBC ≥ 15,000 cells/µL AND/OR • SCr ≥ 1.5 mg/dL

Vancomycin 125 mg PO Q6H for 10 days OR Fidaxomicin 200 mg PO Q12H for 10 days

Characterized by one of the following: • Hypotension • Shock • Toxic Megacolon • Perforation • Ileus

Vancomycin 500 mg PO Q6H OR via NG tube1 AND Metronidazole 500 mg IV Q8H

Alternate only if above agents are unavailable: Metronidazole 500 mg PO TID for 10 days

Clinical and Therapeutic Considerations Ensure loose stools are not a result of laxative Metronidazole should be avoided in patients who are very elderly or infirm Consult ID and Surgery Start supportive care as needed: • IV fluid resuscitation • Electrolyte replacement

If ileus present: Add vancomycin retention enema 500 mg in 100 mL NS Q6H1,2 Treatment duration: 14 days

CDI= Clostridium difficile Infection; H= hour(s); ID= Infectious Diseases; IV= intravenous; NG= nasogastric; NS= normal saline; PO= by mouth; PPI= proton pump inhibitor; Q= every; SCr= Serum Creatinine; WBC= white blood cell

References: 1. McDonald LC, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018. 2. Kim PK, et al. Intracolonic Vancomycin for severe clostridium difficile colitis. Surg Infect (Larchmt). 2013 Dec; 14(6):532-9. 3. Louie T, et al. Fidaxomicin versus Vancomycin for Clostridium difficile Infection. N Engl J Med. 2011 Feb 3;364(5):422-31. 4. Cornely OA, et al. Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial. Lancet Infect Dis 2012; 12: 281–9.

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Clostridium difficile Infection (CDI) Clostridium difficile Infection (CDI) RECURRENT EPISODES No. of Recurrences 1st Recurrence

Recommended Regimens Vancomycin 125 mg PO Q6H for 10-14 days Vancomycin Pulsed-Taper Regimen: 125 mg PO Q6H for 10-14 days 125 mg PO Q12H for 7 days 125 mg PO once daily for 7 days 125 mg PO every 2-3 days for 2-8 weeks OR Fidaxomicin 200 mg PO Q12H for 10 days If fidaxomicin was used for the initial episode:

2nd Recurrence

Vancomycin 125 mg PO Q6H for 1014 days

Consult ID for tailoring antibiotic therapy. Vancomycin Pulsed-Taper Regimen (outlined above) OR Fidaxomicin 200 mg PO Q12H for 10 days OR Consult ID team for possible: • Vancomycin 125 mg PO Q6H for 10-14 days then rifaximin 400mgPO TID for 20 days1, • Referral for fecal microbiota replacement therapy1,

≥ 3 recurrences

Consult ID team • Possible referral for fecal microbiota replacement therapy1 • Consider restarting vancomycin taper OR fidaxomicin 200 mg PO Q12H OR vancomycin followed by rifaximin1 RISK FACTORS FOR CDI

• • • •

≥ 64 years of age Exposure to antibiotics in last 90 days Hospitalization in last 30 days Recent GI surgery

• • • •

Exposure to CDI (household family member with CDI) Long-term care facility or nursing home resident Gastric acid reducing agent (PPIs) Tube feedings

INFECTION CONTROL • • • •

•

Screening for C. difficile in hospitalized patients without diarrhea is not recommended Asymptomatic carriers should not be treated Patients should be placed in a private room or with other patients who have CDI Continue contact precautions for CDI patients until 48 hours from resolution of symptoms • Place contact precautions plus sign on patient’s door • Hand hygiene and barrier precautions (gloves and gowns) • Place dedicated stethoscope in patient’s room When patient discharged or symptoms resolve, room should be terminally cleaned MISCELLANEOUS

•

Repeat CDI PCR testing not recommended due to the likelihood of false positives. Toxin A, B, and TC may remain positive for as long as 30 days in patient with symptom resolution.

CDI= Clostridium difficile infection; GI= gastrointestinal; H= hour(s); ID= Infectious Diseases; PCR= Polymerase Chain Reaction; PO= by mouth; Q= every; TC= Toxigenic Culture

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Extended ExtendedSpectrum Spectrum Beta-Lactamase Beta-Lactamase (ESBL) (ESBL)Infection Infection Extended Spectrum Beta-Lactamase (ESBL) Infection CLINICAL SYNDROME CLINICAL SYNDROME Extended Spectrum Extended Spectrum Beta-Lactamase (ESBL) Beta-Lactamase (ESBL) Infection Infection Carbapenem-resistant Carbapenem-resistant Enterobacteriaceae Enterobacteriaceae (CRE) (CRE)

PREFERRED REGIMEN PREFERRED REGIMEN Meropenem 2 gm IV Meropenem 2 gm IV Q8H Q8H maximum doses) (Use (Use maximum doses) Consult ID Consult ID

ALTERNATIVE REGIMEN ALTERNATIVE REGIMEN Consult ID Consult ID Consult ID Consult ID

Febrile FebrileNeutropenia Neutropenia Febrile Neutropenia CLINICAL SYNDROME CLINICAL SYNDROME Febrile Neutropenia Febrile Neutropenia High risk: anticipated High risk: anticipated prolonged prolonged (>7 days duration) (>7 ANDdays duration) AND profound neutropenia profound (ANC ≤100neutropenia cells/mm3 (ANC ≤100cytotoxic cells/mm3 following following cytotoxic chemotherapy) +/chemotherapy) +/significant co-morbid significant conditions:co-morbid conditions: hypotension, hypotension,new-onset pneumonia, pneumonia,pain, new-onset abdominal or abdominal pain, or neurologic changes neurologic changes

PREFERRED REGIMEN PREFERRED REGIMEN Cefepime 2gm IV Q8H Cefepime 2gm IV Q8H OR OR Piperacillin/tazobactam Piperacillin/tazobactam 3.375gm IV Q4H 3.375gm IV Q4H (18gm/day) (18gm/day)

ALTERNATIVE REGIMEN ALTERNATIVE REGIMEN Meropenem 1 gm IV Meropenem 1 gm IV Q8H Q8H

CLINICAL CONSIDERATIONS CLINICAL CONSIDERATIONS Please DO NOT treat Please DO NOT colonization, or treat a “dirty colonization, urine” sampleor a “dirty urine” sample The optimal treatment Theinfection optimal treatment for due to CRE foruncertain infectionand due to CRE is is uncertain and are antibiotic options antibioticManagement options are limited. limited. Management of infections due to CRE of infections dueinto CRE should be done should be done in ID consultation with consultation with ID

CLINICAL CONSIDERATIONS CLINICAL CONSIDERATIONS If patient has indwelling If patient is has indwelling catheter, persistently catheter, is persistently febrile febrile OR OR previously colonized previously with MRSA:colonized with ADD MRSA: vancomycin ADD vancomycin Consult ID for Consult ID for Anti-fungal therapy; Anti-fungal therapy; Consider when fever Consider when fever fails to respond after failsdays to respond after 3-7 of therapy 3-7 days of therapy

ANC= Absolute neutrophil count; CRE= Extended Spectrum Beta-Lactamase; ESBL= Extended Spectrum Beta-Lactamase; H= hour(s); ID= neutrophil Infectious Diseases; IV= Extended intravenous; MRSA=Beta-Lactamase; Methicillin-Resistant aureus; Q= every Beta-Lactamase; ANC= Absolute count; CRE= Spectrum ESBL=S.Extended Spectrum H= hour(s); ID= Infectious Diseases; IV= intravenous; MRSA= Methicillin-Resistant S. aureus; Q= every NOTE: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Basedbased on Renal Function, Aminoglycoside High Dose Once Daily (HDOD) and on Monitoring in Adult Patients, and NOTE: Dosing on normal renal function. Refer to Table of Contents for section Antimicrobial Dosing for Adult Vancomycin Dosing and Monitoring in Adult Patients. Patients Based on Renal Function, Aminoglycoside High Dose Once Daily (HDOD) and Monitoring in Adult Patients, and Vancomycin Dosing and Monitoring in Adult Patients.

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Fungal Infections Fungal Infections Fungal Infections CONDITION CONDITION Candidemia Candidemia Non-neutropenic Non-neutropenic

Candidemia Candidemia Neutropenic Neutropenic

Urinary Urinary Candidiasis Candidiasis Symptomatic Symptomatic Cystitis Cystitis Urinary Urinary Candidiasis Candidiasis Pyelonephritis Pyelonephritis

PRIMARY THERAPY PRIMARY THERAPY Caspofungin IV Caspofungin LD: 70 mg IV LD: MD:70 50mg mg Q24H MD: OR 50 mg Q24H OR Fluconazole IV Fluconazole LD: 800 mg IV LD: 800 mg (12mg/kg) (12mg/kg) MD: 400 mg MD: 400 mg 6 mg/kg) Q24H 6 mg/kg) Q24H

ALTERNATIVE THERAPY ALTERNATIVE THERAPY L-AmB 3–5 mg/kg IV L-AmB Q24H 3–5 mg/kg IV Q24H OR OR Voriconazole IV/PO Voriconazole IV/PO 400 mg 400 mg Q12H for (6 mg/kg) (6doses mg/kg) Q12H 2 then 200for mg 2 then 200 mg (3doses mg/kg) Q12H (3 mg/kg) Q12H

DURATION DURATION 14 days after 14 after firstdays negative first negative culture result culture AND result AND resolution of resolution of signs/symptoms signs/symptoms

COMMENTS COMMENTS Remove all IV Remove allifIV catheters, catheters, possible if possible Consult ID Consult ID Consider eye Consider eye exam exam Transition to Transition fluconazoletois fluconazole is for recommended recommended clinically stable for clinically stable patients with patients with fluconazole fluconazole susceptible susceptible isolates AND isolates AND negative repeat negative repeat blood cultures blood cultures Caspofungin IV Fluconazole IV Fluconazole is 14 days after Caspofungin Fluconazole IV mg/kg) 14 Fluconazole after LD: 70 mg IV LD: 800 mg (12 preferred in is firstdays negative LD: LD: mg/kg) first preferred in negative MD:70 50mg mg Q24H MD:800 400mg mg(12 (6 mg/kg) patients without culture result MD: 50 mg Q24H MD: patients without AND result OR recent azole Q24H400 mg (6 mg/kg) culture AND OR Q24H recent azole L-AmB OR resolution of exposure AND L-AmB OR resolution of exposure AND IV/PO who are NOT 3–5 mg/kg IV Q24H Voriconazole signs/symptoms IV/PO are NOT 3–5 mg/kg IV Q24H Voriconazole signs/symptoms critically ill. 400 mg (6 mg/kg) and neutropenia who 400 mgfor(62mg/kg) Q12H doses then and neutropenia critically ill. Remove IV Q12H doses then 200 mgfor(32mg/kg) Remove IVif catheters, 200 mg (3 mg/kg) Q12H catheters, possible if Q12H possible Consult ID Consult ID Consider eye Consider eye exam exam Fluconazole Conventional Fluconazole: Alternative Fluconazole Conventional Fluconazole: Alternative 200 mg (3 mg/kg) Amphotericin B 14 days treatment is 200 mg (3 mg/kg) Amphotericin days is for PO Q24H 0.3–0.6 mg/kgBIV Q24H 14 Amphotericin B: treatment recommended PO Q24H 0.3–0.6 mg/kg IV Q24H Amphotericin B: recommended for 1-7 days fluconazole 1-7 days fluconazole resistant resistant organisms organisms Fluconazole Conventional Fluconazole: Alternative Fluconazole: Conventional Fluconazole Alternative 14 days 200–400 mg (3–6 Amphotericin B treatment is Amphotericin days 200–400PO mg (3–6 is for Amphotericin B: treatment mg/kg) Q24H 0.5–0.7 mg/kgBIV Q24H 14 recommended 0.5–0.7 mg/kg IV Q24H Amphotericin B: recommended mg/kg) PO Q24H for 14 days fluconazole 14 days fluconazole resistant resistant organisms organisms

H= hour(s); ID= Infectious Diseases; IV= intravenous; L-AmB= Liposomal Amphotericin B; LD= loading dose; MD= maintenance dose; PO= by mouth; Q= every H= hour(s); ID= Infectious Diseases; IV= intravenous; L-AmB= Liposomal Amphotericin B; LD= loading dose; MD= maintenance dose; PO= by mouth; Q= every NOTE: Some agents will require ID consult/approval (amphotericin B, caspofungin, voriconazole). Refer to Table of Contents for section onagents Guidelines for Restricted Antibiotics (amphotericin B, caspofungin, voriconazole). Refer to Table of Contents NOTE: Some will require ID consult/approval for section on Guidelines for Restricted Antibiotics

References: 1. Pappas PG, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. References: Clin Infect 2016; 62(4):e1-e50. 1. Pappas PG,Dis. et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016; 62(4):e1-e50.

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Fungal Infections

C P T A Fungal Infections Fungal Infections ONDITION

Nongenital Oropharyngeal CONDITION (Oral Thrush) Nongenital Oropharyngeal (Oral Thrush)

Esophageal Candidiasis Esophageal Candidiasis

LTERNATIVE THERAPY

RIMARY HERAPY

Clotrimazole 10 mg troche 5 times daily PRIMARY THERAPY OR Clotrimazole 10 mg Nystatin suspension troche 5 times daily PO four times a day OR OR Nystatin suspension Fluconazole PO four times a day 100–200 mg OR PO once daily Fluconazole Fluconazole 100–200 mg 200–400 mg PO once daily (3–6 mg/kg) Fluconazole PO Q24Hmg 200–400 (3–6 mg/kg) PO Q24H

DURATION

Itraconazole oral solution ALTERNATIVE THERAPY 200 mg PO once Itraconazole oral daily OR solution Voriconazole 200daily mg 200 mg PO once PO Q12H OR

Uncomplicated disease 7 to 14 DURATION days Uncomplicated

Caspofungin IV LD: 70 mg MD: 50 mg Q24H Caspofungin IV OR 70 mg LD: Conventional MD: 50 mg Q24H Amphotericin B OR 0.3–0.7 mg/kg IV Conventional Q24H Amphotericin B

14–21 days

disease 7 to 14 days

Voriconazole 200 mg PO Q12H

0.3–0.7 mg/kg IV General Susceptibility Patterns of Candida spp. Q24H Amphotericin Fluconazole Itraconazole General Susceptibility Patterns of Candida spp. B

14–21 days

COMMENTS Refractory disease: COMMENTS Voriconazole Refractory 200 mg PO Q12H disease: OR Voriconazole L-AmB 200 mg PO Q12H suspension 1 mL OR of 100 mg/mL L-AmB four times a1day suspension mL Patients unable of 100 mg/mL to tolerate oral four times aan day agent, IVunable Patients fluconazole ororal to tolerate an alternative agent, IV agent listed may be fluconazole or used. alternative agent listed may be used.

Caspofungin

Voriconazole

S Fluconazole

S Itraconazole

Amphotericin S B

S Caspofungin

S Voriconazole

Candida C. tropicalis albicans C. C. tropicalis parapsilosis

S S

C. C. glabrata parapsilosis C. krusei C. glabrata C. lusitaniae C. krusei

S S-DD

S-DDS to R

S S-I

S-DDS to R

R S-DD S R

S-DD to R S-DD to R S S-DD to R

S-I S-I S to R S-I

S S S S

S S-DD to R S S

Candida albicans

H= hour(s); I= Intermediate; IV= intravenous; L-AmB= Liposomal Amphotericin B; LD= loading dose; MD= maintenance dose;

C. lusitaniae S S-DD= Susceptibility S to Ris dose dependent;Sspp= species PO= by mouth; Q= every; R=S Resistant; S= susceptible;

H= hour(s); I=agents Intermediate; IV= intravenous; L-AmB= Liposomal Amphotericin B; LD= voriconazole). loading dose; MD= dose; NOTE: Some will require ID consult/approval (amphotericin B, caspofungin, Refermaintenance to Table of Contents PO= by mouth; Q= every; R= susceptible; S-DD= Susceptibility is dose dependent; spp= species for section on Guidelines forResistant; RestrictedS=Antibiotics NOTE: Some agents will require ID consult/approval (amphotericin B, caspofungin, voriconazole). Refer to Table of Contents for section on Guidelines for Restricted Antibiotics

References: 1. Pappas PG, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016; 62(4):e1-e50. References: 1. Pappas PG, et al. Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases SocietyPAGE of America. Clin Infect Dis. 2016; 62(4):e1-e50.

Influenza Influenza A andABand (Flu) B (Flu) CLINICAL AND THERAPEUTIC ALGORITHM Diagnosis is based on the clinical presentation of the patient and results of RT-PCR. Decision to initiate treatment should NOT wait for confirmation of laboratory results.

CLINICAL SEVERITY

Select ONE of the following: • Oseltamivir 75 mg PO Q12H for 5 days • Zanamivir 10 mg (two 5 mg inhalations) Q12H for 5 days • Peramivir 600 mg IV as a single dose (via >15 minute infusion) • Baloxavir -If 40 - <80 kg: 40 mg PO as a single dose -If ≥80 kg: 80 mg PO as a single dose

Treatment – severe or complicated outpatient

Oseltamivir 75 mg PO Q12H for 5 days

Treatment inpatient

Oseltamivir 75 mg PO Q12H for 5 days

Continue the full course of treatment if first RT-PCR is negative and if signs and symptoms indicate influenza due to possibility of false negative. History of influenza vaccination does not preclude influenza when signs and symptoms are compatible with the clinical syndrome. Antiviral treatment recommended as early as possible for patient who (any of the following): • is hospitalized* • has severe, complicated, or progressive illness* • is at high risk for complications *PO oseltamivir recommended antiviral High risk complications (any of the following): • ≥65 years • Chronic health conditions** • Immunosuppression, including caused by medication or HIV infection • Pregnant or postpartum (within 2 weeks of delivery) women (PO oseltamivir preferred for treatment of pregnant women) • American Indian/Alaska Natives • Body mass index ≥40 • Residents of nursing homes and other chronic-care facilities • People younger than 19 years old who are receiving long-term aspirin- or salicylatecontaining medication Zanamivir is not recommended in people with underlying respiratory disease (e.g. asthma, COPD.) Can consider antiviral treatment previously healthy, symptomatic outpatient NOT at high risk based on clinical judgement (within 48 hours of symptom onset)

RECOMMENDED REGIMENS

Treatment – uncomplicated outpatient

Notes for treatment: Antivirals should be started as early as possible within 48 hours of symptom onset. May be some benefits for severe, complicated or progressive illness, and in hospitalized patients when started after 48 hours of illness onset. Longer daily dosing (PO oseltamivir or IV peramivir) can be considered for patients who remain severely ill after 5 days of treatment. Post-Exposure Chemoprophylaxis

Select ONE of the following: • Oseltamivir 75 mg PO once daily • Zanamivir 10 mg (two 5 mg inhalations) once daily Treat for 7 days

Notes for chemoprophylaxis: CDC recommends duration of 7 days (after last known exposure). For control of outbreaks, CDC recommends chemoprophylaxis for a minimum of 2 weeks, and continuing up to 1 week after the last known case was identified.

CDC= Centers for Disease Control and Prevention; COPD= chronic obstructive pulmonary disease; H= Hour(s); HIV= human immunodeficiency virus; PO= by mouth; Q= every; RT-PCR= reverse transcriptase polymerase chain reaction **Chronic pulmonary (including asthma), cardiovascular (except hypertension alone), renal, hepatic, hematological (including sickle cell disease), metabolic disorders (including diabetes mellitus), neurologic conditions (disorders of the brain, spinal cord, nerve, muscle, epilepsy, stroke, or intellectual disability) NOTE: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function. A reduction in the dose of oseltamivir and peramivir is recommended with renal impairment

References: 1. Centers for Disease Control and Prevention. Influenza Antiviral Medications: Summary for Clinicians. Current for the current for the 2018-2019 influenza season. https://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm

PAGE 9

â&#x20AC;&#x201A;Intra-abdominal Infections Intra-abdominal Infections CLINICAL SYNDROME Intra-abdominal Infections Community acquired OR Hospital acquired

PREFERRED REGIMEN

ALTERNATIVE REGIMEN

CLINICAL CONSIDERATIONS

Piperacillin/tazobactam 3.375 gm IV Q6H

Ciprofloxacin 400 mg IV Q12H +/- Metronidazole 500 mg IV Q8H

Piperacillin/tazobactam provides excellent anaerobic coverage, addition of clindamycin OR metronidazole is NOT indicated or necessary

Meropenem 1gm Q8H

*If a patient has a history of multi-drug resistant Gramnegative organisms, suggest an ID Consult H= hour(s); ID= Infectious Diseases; IV= intravenous; Q= every NOTE: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function, Aminoglycoside High Dose Once Daily (HDOD) and Monitoring in Adult Patients, and Vancomycin Dosing and Monitoring in Adult Patients.

PAGE 10

â&#x20AC;&#x201A;Lyme Disease Lyme Disease CLINICAL SYNDROME Intra-abdominal Lyme Disease Infections Early disease Community acquired OR Hospital acquired

PREFERRED REGIMEN

ALTERNATIVE REGIMEN

CLINICAL CONSIDERATIONS

Piperacillin/tazobactam Doxycycline 100 mg PO 3.375 Q12H*gm IV Q6H OR Amoxicillin 500 mg PO Q8H*

Consult ID 400 mg IV Ciprofloxacin Q12H Cefuroxime 500 mg PO +/Metronidazole Q12H* 500 mg isIVsecond-line Q8H for early disease Meropenem 1gm Q8H

Piperacillin/tazobactam Relapse may occur with provides excellent any regimen; patients anaerobic coverage, with objective addition of clindamycin signs/symptoms may metronidazole is OR need a second course NOT indicated or Duration of Treatment: necessary Doxycycline 10-21 days Amoxicillin/Cefuroxime 14-21 days Lyme antibody testing can be negative in first 6 weeks Consider co-infection with anaplasma or babesia

Late disease with central OR peripheral nervous system disease

Consult ID Requires IV ceftriaxone 2g daily x 28 days OR in some cases, PO doxycycline 100 mg BID may be considered a reasonable alternative

Cardiac manifestations of Lyme

Consult ID Typically requires IV Ceftriaxone 2g daily until cardiac manifestations (eg. Heart block) resolve, THEN can consider PO doxycycline 100 mg BID for total treatment duration of 21-28 days

Septic arthritis secondary to Lyme disease

Consult ID Typically requires 28 days of therapy with IV Ceftriaxone 2g daily OR PO Doxycycline 100 mg BID, consider retreatment if arthritis symptoms persist.

Duration of Treatment: 28 days

Duration of Treatment: 21-28 days

Duration of Treatment: 28 days

H= hour(s); ID= Infectious Diseases; IV= intravenous; PO= By Mouth; Q= every *Doxycycline also has activity against Ehrlichia and Anaplasma. Amoxicillin and cefuroxime do not. NOTE: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function, Aminoglycoside High Dose Once Daily (HDOD) and Monitoring in Adult Patients, and Vancomycin Dosing and Monitoring in Adult Patients.

PAGE 11

Pneumonia Respiratory Tract: Pneumonia START HERE Does the patient presenting with pneumonia have any risk factors for multidrug resistant organisms (MDROs): • •

Hospitalized for ≥ 2 days within previous 90 days Resides in a nursing home OR long-term care facility, OR skilled nursing facility

• • •

Received recent antibiotic therapy (previous 90 days), chemotherapy, OR wound care within previous 30 days Chronic hemodialysis Have immunosuppressive disease OR receiving immunosuppressing medications

CLINICAL CONSIDERATIONS • • • •

Infiltrate on chest x-ray required for pneumonia diagnosis Collect BAL OR PSB OR Sputum AND blood cultures prior to starting antimicrobial therapy Re-assess antibiotic therapy on day 2 or 3 when cultures return from microbiology lab Specific isolated pathogens should prompt clinicians to de-escalate treatment based on the pathogen's susceptibility pattern NO RISK FACTORS FOR MDROS

INPATIENT NON-ICU Ceftriaxone 1 gm IV Q24H AND Azithromycin 500 mg PO/IV for 1 day, then 250 mg PO/IV Q24H for 4 days OR Moxifloxacin 400 mg IV/PO Q24H INPATIENT ICU Ceftriaxone 2 gm IV Q24H AND Moxifloxacin 400 mg IV Q24H OR Ampicillin/sulbactam 3 gm IV Q6H AND Moxifloxacin 400 mg IV Q24H OR Penicillin-allergic patients: Aztreonam 2 gm IV Q8–12H AND Moxifloxacin 400 mg IV Q24H

RISK FACTORS FOR MDROS INPATIENT ICU Beta-lactam/beta-lactamase inhibitor: Piperacillin-tazobactam 3.375 gm IV Q4H† OR Piperacillin-tazobactam 4.5 gm IV Q6H OR Cephalosporin: Cefepime 2g IV Q8H OR Antipseudomonal carbapenem: Meropenem 1 gm IV Q8H PLUS If at risk for resistant gram-negative:†† Antipseudomonal fluoroquinolone: Levofloxacin 750 mg IV Q24H Ciprofloxacin 400 mg IV Q8H PLUS If at risk for MRSA: Vancomycin 15 mg/kg IV‡ OR Linezolid 600 mg IV/PO Q12H (See Criteria for Use) Treat accordingly based on risk factors and microbiologic history

BAL= Bronchoalveolar Lavage; BP= blood pressure; bpm= beats or breaths per minute; CrCl= Creatinine Clearance; H= hour(s); IBW= ideal body weight; IV= intravenous; MDRO= multi-drug resistant organism; MRSA= Methicillin-Resistant S. aureus; PO= by mouth; PSB= Protected Specimen Brush; Q= every †Suspect P.

Q8H.

aeruginosa: CrCl >50 ml/min = 3.375 gm q4h; CrCl 50-10 ml/min = 3.375 gm IV Q6H; CrCl < 10 ml/min = 3.375 gm

††If hospital-acquired or ventilator-associated and 1) had IV antibiotics in previous 90 days, or 2) if ventilator-associated with hospitalization for >5 days prior to pneumonia, in septic shock, has acute respiratory distress syndrome, or in requiring acute renal replacement. ‡Refer to

Table of Contents for section on vancomycin and aminoglycoside dosing and monitoring

Note: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function.

PAGE 12

Respiratory Tract: Pneumonia

NO R F Pneumonia Respiratory Tract:MDRO Pneumonia ISK ACTORS FOR

OUTPATIENT RISK FAND ACTORS MDROSuse in PreviouslyNO healthy noFOR antibiotic previous 90 days: OUTPATIENT Doxycycline 100 mgAND PO Q12H for 5 days Previously healthy no antibiotic use in OR previous 90 days: Azithromycin 500 mg PO for 1 dose, then Doxycycline 100 mg PO Q12H for 5 days 250 mg PO Q24H for 4 days OR Azithromycin 500 mg PO for 1 dose, then OUTPATIENT 250 mg PO Q24H for 4 days Presence of ≥ 1 co-morbidities* OR antibiotic use in previous 30 days: OUTPATIENT

RISK FACTORS FOR MDROS

OUTPATIENT RISK Fbased ACTORSon FOR MDRO S and Treat accordingly risk factors microbiologic history OUTPATIENT Consider paging Infectious Treat accordingly based on Diseases risk factors and microbiologic history Consider paging Infectious Diseases

Amoxicillin/clavulanate 875 mg PO Presence of ≥ 1 co-morbidities* ORQ12H antibiotic for 7 days 30 days: use5intoprevious AND Amoxicillin/clavulanate 875 mg PO Q12H Azithromycin 500 mg PO for 1 dose, then for 5 to 7 days 250 mg PO Q24H for 4 days AND Azithromycin 500 mg PO for 1 dose, then OR 250 mg PO Q24H for 4 days Moxifloxacin++ 400 mg PO Q24H for 5 to 7 days OR Moxifloxacin++ 400 mg PO Q24H for 5 toT7HERAPY days CONSIDERATIONS • •

Cough and chest X-ray may take 4 to 6 weeks to improve/change THERAPY CONSIDERATIONS Duration of therapy • Community-acquired pneumonia: 5–7 days • Cough and chest X-ray may take 4 to 6 weeks to improve/change • Hospital-acquired pneumonia, ventilator-associated pneumonia: 7–8 days; provided that • Duration of therapy the targeted pathogen is identified based on bronchoscopy and the etiologic pathogen is • Community-acquired pneumonia: 5–7 days not P. aeruginosa, and that the patient is: afebrile for 48 to 72 hours • Hospital-acquired pneumonia, ventilator-associated pneumonia: 7–8 days; provided that AND ≤ 1 of the following: the targeted pathogen is identified based on bronchoscopy and the etiologic pathogen is HR >100 bpm, RR >24 bpm, BP < 90 mmHg (systolic), O2 sat <90%, altered mental status not P. aeruginosa, and that the patient is: afebrile for 48 to 72 hours AND ≤ 1 of the following: BP= blood pressure; bpm= beatsRR or breaths per minute; H=mmHg hour(s); (systolic), HR= heart rate; MDRO= multi-drug satintravenous; <90%, altered mental status HR >100 bpm, >24 bpm, BP < 90 O2 IV= resistant organism; PO= by mouth; Q= every; RR= respiratory rate

*Presence of comorbidities: chronic heart, lung, liver or renal disease; diabetes; alcoholism; malignancies; asplenia; BP= blood pressure; bpm= beatsor ormedications breaths per minute; H= hour(s); HR= heart rate; IV= intravenous; MDRO= multi-drug immunosuppressing conditions resistant organism; PO= by mouth; Q= every; RR= respiratory rate ++Although are frequently used, their is disease; discouraged in ambulatory patients without comorbid *Presence offluoroquinolones comorbidities: chronic heart, lung, liver or use renal diabetes; alcoholism; malignancies; asplenia; conditions or recent antimicrobial use unless an alternative regimen is not feasible. The risk of adverse effects (including the immunosuppressing conditions or medications risk of Clostridium difficile infection) and the risk of selection for resistance in colonizing organisms, are generally thought to be greater with fluoroquinolones ++Although fluoroquinolones are frequently used, their use is discouraged in ambulatory patients without comorbid conditions or based recenton antimicrobial use unless anRefer alternative is notfor feasible. TheAntimicrobial risk of adverse effects Note: Dosing normal renal function. to Tableregimen of Contents section on Dosing for(including Adult the risk of Clostridium difficile infection) and the risk of selection for resistance in colonizing organisms, are generally thought to Patients Based on Renal Function. be greater with fluoroquinolones Note: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function.

References: 1. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72 2. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, References: ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005 Feb 15;171(4):388-416. 1. Mandell LA, Wunderink RG, Anzueto al. InfectiousofDiseases Society of America/American Thoracic Society consensus guidelines on the 3. Kalil AC, Metersky ML, Klompas M. etA,al.etManagement Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical management of community-acquired pneumonia in adults. Clin Infect Dis.American 2007 MarThoracic 1;44 Suppl 2:S27-72 Practice Guidelines by the Infectious Diseases Society of America and the Society. Clin Infect Dis 2016;63:1-51. 2. American Thoracic Society; Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005 Feb 15;171(4):388-416. 3. Kalil AC, Metersky ML, Klompas M. et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia:PAGE 2016 Clinical 13 Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;63:1-51.

Proton-Pump Inhibitor Proton-Pump Inhibitor (PPI) Use(PPI) Use The FDA has issued multiple warnings on the long-term use of PPIs. These include: increased risk of C. difficile infection1, hypomagnesemia2, and fractures of the hip, wrist, and spine3. Therefore, prudent prescribing of PPIs is warranted. The FDA recommends use of the lowest dose and shortest duration of PPI therapy appropriate for the condition being treated1-3. Patient compliance, time of administration (prior to meals), and dietary indiscretions (i.e. alcohol or irritating foods) should be assessed prior to titration of PPI doses. Indication

Treatment

Gastroesophageal reflux disease (GERD)6 Symptomatic relief Acute healing of erosive or ulcerative esophagitis Maintenance healing of erosive or ulcerative esophagitis

Stress ulcer prophylaxis Reserve PPIs for critically ill patients with increased risk of bleeding:4,5 At least one of the following: - Coagulopathy (platelet count <50,000 mm3, INR >1.5, or aPTT >2x control) - Mechanical ventilation >48 hours - History of GI ulceration or bleeding within past year - Glasgow Coma score <10 - Traumatic, severe thermal or spinal cord injury - Hepatic failure Two or more minor risk factors: - Sepsis - ICU stay ≥1 week - Occult GI bleeding ≥6 days - High-dose corticosteroids (>250 mg/day hydrocortisone equivalent)

Duration Initial 8 week course for symptom relief or esophagitis

Omeprazole 20 mg PO once daily OR Pantoprazole 40mg PO once daily

Maintenance therapy determined by response and severity of disease For patients that require more long-term therapy, consider a trial of a lower dose, on-demand therapy, or intermittent therapy to minimize exposure Transition to PO when possible Continue until resolution of underlying risk factors and/or critical illness

Omeprazole 20-40 mg once daily OR Pantoprazole 40mg IV/PO once daily

Recommend discontinuation at discharge, unless there is another indication for use

aPTT= activated partial thromboplastin time; GERD= Gastroesophageal reflux disease; GI= Gastrointestinal; ICU= intensive care unit; INR= International normalized ratio; IV= intravenous; PO= by mouth; PPI= proton pump inhibitor References 1. U.S. Food and Drug Administration (FDA). FDA Drug Safety Communication: Clostridium difficile-associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs) [internet]. Updated May 2012 [cited 11/21/12]. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm290510.htm 2. U.S. Food and Drug Administration (FDA). FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs (PPIs) [internet]. Updated February 2012 [cited 11/21/12]. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm245011.htm. 3. U.S. Food and Drug Administration (FDA). FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors [internet]. Updated March 2011 [cited 11/21/12]. Available from: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm 4. ASHP Therapeutic Guidelines on Stress Ulcer Prophylaxis. ASHP Commission on Therapeutics and approved by the ASHP Board of Directors on November 14, 1998. Am J Health Syst Pharm 1999; 56:347. 5. Spirt MJ, Stanley S. Update on stress ulcer prophylaxis in critically ill patients. Crit Care Nurse 2006; 26:18. 6. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013;108:308-28.

PAGE 14

Procalcitonin (PCT) Please note: This test should NOT be used as a sole diagnostic tool to guide antimicrobial therapy, and should NOT supersede clinical judgment. BACKGROUND: Procalcitonin (PCT) is a biomarker produced in large quantities during systemic inflammation, particularly during bacterial infection. PCT rises with severity of infection, and persistently high levels are associated with poor prognosis. CRITERIA FOR USE: • Lower Respiratory Tract Infections (See Algorithm’s 1 & 2, next page): Acute signs and symptoms consistent with a respiratory pathology where bacterial pneumonia, viral pneumonia, COPD exacerbation, bronchitis, congestive heart failure, or other diagnostic uncertainties are part of the differential diagnosis • Sepsis (See Algorithm 3 & 4, next page): SIRS criteria, sepsis, severe sepsis or septic shock UNACCEPTABLE USES • Non-systemic or localized infections (e.g. mild skin and soft tissue infections, uncomplicated urinary tract infections) • As a sole diagnostic tool for infection. Results should be interpreted in context of clinical picture. Courtesy of Thermo Fisher

KEY PRINICPLES FOR USE AND LIMITATIONS 1. Results should be interpreted in context of clinical picture. For example, do not withhold antibiotics in septic patients with normal PCT; likewise, it is reasonable to monitor patients without signs/symptoms of infection off antimicrobials despite mildly elevated PCT. 2. Serial measurements are preferred to determine the need for antibiotic therapy, or to guide discontinuation of therapy. Patients with consistently normal/low PCT levels are unlikely to have infection, and other diagnoses should be considered. 3. Be cognizant of clinical situations that can cause falsely high or normal PCT levels.

Potential causes of FALSELY HIGH results • • • • • • •

Major stress (i.e. severe trauma, surgery, cardiac shock) Administration of cytokine-stimulating agents Some fungal infections; malaria Prolonged, severe cardiogenic shock or organ perfusion abnormalities Some forms of vasculitis, and acute graft versus host disease Paraneoplastic syndromes (medullary thyroid & small cell lung cancer ) Significant renal dysfunction (e.g. ESRD on hemodialysis)

Potential causes FALSELY NORMAL/LOW results • Localized infections (i.e. non-systemic) • Subacute infections • Early infection (i.e. need for PCT repeat)

COPD= chronic obstructive pulmonary disease; ESRD= end-stage renal disease; ID= infectious diseases; LRTI = lower respiratory tract infection; L= liters; mcg= micrograms; SIRS= systemic inflammatory response syndrome

Procalcitonin (PCT) Please note: This test should NOT be used as a sole diagnostic tool to guide antimicrobial therapy, and should NOT supersede clinical judgment.

LOWER RESPIRATORY TRACT INFECTIONS (LRTI)

Algorithm 1: Interpretation of BASELINE result for LRTI Initial PCT result

<0.1mcg/L

0.1-0.24mcg/L

≥0.25-0.5mcg/L

>0.5mcg/L

Antibiotic Use Recommendation

Strongly discouraged

Discouraged

Encouraged

Strongly Encouraged

• • LRTI Follow-up •

Consider alternative diagnosis Repeat PCT in 6-12 hours if no clinical improvement and antibiotics were not initiated If clinically unstable, consider overruling

• •

Repeat every 2-3 days to consider early antimicrobial discontinuation Please See Algorithm 2 for follow-up result interpretation

Algorithm 2: Interpretation of FOLLOW-UP result for LRTI Follow-up PCT result Antibiotic Use Recommendation

<0.1mcg/L or decreased by >90% Discontinuation strongly encouraged •

LRTI Follow-up

0.1-0.24mcg/L or decreased by >80% Discontinuation encouraged

Consider continuation if clinically unstable

• •

≥0.25-0.5mcg/L

>0.5mcg/L

Discontinuation discouraged

Discontinuation strongly discouraged

If PCT remains high, consider treatment failure Further diagnostic evaluation and treatment alterations may be warranted

SEPSIS (SIRS, sepsis, severe sepsis, septic shock)

Strongly consider initiating antibiotics in all septic patients with high suspicion for infection, regardless of PCT level!!! Algorithm 3: Interpretation of BASELINE result for SEPSIS Initial PCT result

<0.25mcg/L

0.25-0.49mcg/L

≥0.5mcg/L

≥1mcg/L

Antibiotic Use Recommendation

Strongly discouraged

Discouraged

Encouraged

Strongly Encouraged

Sepsis Follow-up

• • •

Consider alternative diagnosis Repeat PCT in 6-12 hours if antimicrobials were not initiated If clinically unstable, consider overruling

• •

Repeat DAILY for 2-3 days to consider early antimicrobial discontinuation Please See Algorithm 4 for follow-up result interpretation

Algorithm 4: Interpretation of FOLLOW-UP result for SEPSIS

<0.25mcg/L

Follow-Up PCT result Antibiotic Use Recommendation

Discontinuation strongly encouraged •

Sepsis Follow-up

0.25-0.49mcg/L or decreased by >80% Discontinuation encouraged

Consider continuation in clinically unstable patients

≥0.5mcg/L and decreased by <80% Discontinuation discouraged •

•

≥0.5mcg/L and increasing or not decreasing Discontinuation strongly discouraged

PCT level that is increasing or not decreasing by at least 10% per day is a poor prognostic factor and indicator of uncontrolled infection May consider further diagnostic evaluation, or broadening therapy, although routine broadening not recommended. Consider ID Consult.

COPD= chronic obstructive pulmonary disease; ESRD= end-stage renal disease; ID= infectious diseases; LRTI= lower respiratory tract infection; L= liters; mcg= micrograms; SIRS= systemic inflammatory response syndrome

Respiratory Tract: Acute Bacterial Sinusitis Respiratory Respiratory Tract: Acute Bacterial Sinusitis Tract: Acute Bacterial Sinusitis CLINICAL AND THERAPEUTIC RISK FACTORS RECOMMENDED REGIMENS ALGORITHM CLINICAL AND THERAPEUTIC RISK FACTORS of Risk 1a. Antibiotics are indicated if the Presence ALGORITHM Factors for patient has ANY of the Antibioticof Risk 1a. following: Antibiotics are indicated if the Presence Resistance: • Symptoms lasting Factors for patient has ANY of the≥ 10 • Age > 65 days without clinical Antibiotic following: • Antibiotics improvement Resistance: • Symptoms lasting ≥ 10 within last 30 ORdays without clinical • Age > 65 days • improvement Severe symptoms at onset • Antibiotics • within Hospitalization last 30 ORlasting within last 5 ≥ 3 days [Fever (≥ at 102 °F), days • Severe symptoms onset days severe • Hospitalization lasting facial pain, or • within Immunopurulent last 5 ≥ 3 days discharge] [Fever (≥ 102 °F), compromised ORsevere facial pain, or days • purulent New onset fever, severe •ORImmunodischarge] • compromised Fever > 102°F ORheadache, or increase nasalonset discharge after 5-6 ORwith signs of • New fever, severe days following initial systemic illness headache, or increase • Fever > 102°F improvement nasal discharge after 5-6 with signs of None of the above days following initial systemic illness 1b. If the patient does not meet risk factors for improvement this criteria likely viral and antibiotic None of the above 1b. self-limiting. If the patientMay doesprovide not meet resistance risk factors for symptom relief. this criteria likely viral and antibiotic AND •self-limiting. Reduce nasal Maysymptoms: provide resistance topical relief. or nasal symptom No fever or signs of AND decongestants, intranasal • Reduce nasal symptoms: systemic illness corticosteroids, topical or nasal intranasal No fever or signs of saline decongestants, intranasal systemic illness corticosteroids, intranasal 2. If no improvement after 3 to 5 saline days of antibiotic therapy to an alternative 2. switch If no improvement afteragent 3 to 5 from of a different days antibioticantibiotic therapy class switch to an alternative agent CrCl= creatinine clearance; H= hour(s); PO= by mouth; Q= every from a different antibiotic class

RECOMMENDED REGIMENS Initial Empiric Antibiotic Therapy: Amoxicillin/clavulanate PO: Initial Empiric Antibiotic Therapy: CrCl > 30 ml/min: 2000/125 mg‡ Amoxicillin/clavulanate PO: Q12H ‡ 29 ml/min: 875/125 CrCl >1030– ml/min: 2000/125 mgmg Q12H ‡ mg CrCl 10 < 10– ml/min: 2000/125 29 ml/min: 875/125 mg Q24H Q12H Alternatives*: CrCl < 10 ml/min: 2000/125‡ mg Moxifloxacin 400 mg PO Q24H Q24H Alternatives*: Treat for 7 to 10 days Moxifloxacin 400 mg PO Q24H Treat for 7 to 10 days

No risk for Antibiotic Resistance: Amoxicillin/clavulanate PO: No risk for Antibiotic Resistance: CrCl > 30 ml/min: 875/125 mg Q12H Amoxicillin/clavulanate PO: CrCl 10–29 ml/min: 500/125 mg Q12H> 30 ml/min: 875/125 mg Q12H CrCl < 10 ml/min: 875/125 mgmg Q24H CrCl 10–29 ml/min: 500/125 Alternatives*: Q12H Doxycycline 100 mg PO Q12H CrCl < 10 ml/min: 875/125 mg Q24H Alternatives*: Treat for 5 to 7 days Doxycycline 100 mg PO Q12H Treat for 5 to 7 days

‡ Pharmacy does not carry amoxicillin/clavulanate 2000/125 mg tablets. Order 875/125 mg tablets of amoxicillin/clavulanate CrCl= creatinine clearance; H= hour(s); PO= by mouth; Q= every AND 1000 mg tablets of amoxicillin (total amoxicillin/clavulanate = 1,875/125 mg per dose). ‡ Pharmacy does not carry amoxicillin/clavulanate 2000/125 mg tablets. Order 875/125 mg tablets of amoxicillin/clavulanate AND 1000 mgtrimethoprim-sulfamethoxazole, tablets of amoxicillin *Macrolides, and 2nd or 3rd generation cephalosporins are not recommended due to (total amoxicillin/clavulanate = 1,875/125 increasing rates of antimicrobial resistance.mg per dose). *Macrolides, trimethoprim-sulfamethoxazole, and 2nd or 3rd generation cephalosporins are not recommended due to increasing rates of antimicrobial resistance.

References: 1. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults. Clin Infect Dis. 2012; 54:e72. References: 1. Chow AW, Benninger MS, Brook I, et al. IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and PAGE 16 adults. Clin Infect Dis. 2012; 54:e72.

Respiratory Tract: Acute Pharyngitis Respiratory Tract: Acute Pharyngitis Respiratory Tract: Acute Pharyngitis QUICK FACTS : 1-2

• OnlyFACTS 5-15%1-2of: adult cases of acute pharyngitis are caused by Group A β-hemolytic QUICK streptococci (GAS). • Only 5-15% of adult cases of acute pharyngitis are caused by Group A β-hemolytic • It is estimated that 3,000 to 4,000 patients with GAS must be treated for every 1 streptococci (GAS). case of acute rheumatic prevented. • It is estimated that 3,000fever to 4,000 patients with GAS must be treated for every 1 • case Antibiotic therapy of GASfever hastens resolution by 1-2 days if initiated within 2-3 days of acute rheumatic prevented. of symptom onset.of GAS hastens resolution by 1-2 days if initiated within 2-3 days • Antibiotic therapy of symptom onset.

CLASSIFICATION

CLINICAL PRESENTATION

CLASSIFICATION Group A β-hemolytic Group A streptococcus β-hemolytic (GAS) streptococcus (GAS)

CLINICAL PRESENTATION ≥ 2 of the following: • Fever (≥ 100.4°) ≥ of the following: • 2 Tonsillar exudates •• Fever (≥ 100.4°) No cough •• Tonsillar exudates Tender anterior • No cough cervical • Tender anterior lymphadenopathy cervical (lymphadenitis) • lymphadenopathy Scarlatiniform rash (lymphadenitis) • Scarlatiniform rash

Viral Pharyngitis

• • •• •• •• •• • ••

RECOMMENDED REGIMENS RECOMMENDED REGIMENS Amoxicillin 500 mg PO Q12H Amoxicillin 500 mg PO OR Q12H Penicillin VK 250 mg Q6H OR OR Penicillin VK 250 Penicillin 500 mg mg PO Q6H Q12H OR For 10 days Penicillin 500 mg PO Q12H Penicillin Allergy For 10 days Non-anaphylactic allergy: Penicillin Allergy Cephalexin 500 mg PO Non-anaphylactic Q12H x 10 days allergy: Cephalexin 500 mg PO OR Q12H x 10 days Clindamycin 300 mg PO OR Q6H for 10 days Clindamycin 300 mg PO OR Q6H for 10 days Azithromycin 500 mg PO x OR 1 day, then 250 mg PO Azithromycin Q24H x 4 days500 mg PO x 1 day, then 250 mg PO Q24H x 4 days Supportive treatment (antipyretic OR analgesic) Supportive treatment (antipyretic OR analgesic)

CLINICAL CONSIDERATIONS CLINICAL CONSIDERATIONS Clinical suspicion for GAS: Clinical suspicion Obtain throat swab for GAS: GAS rapid OR order Obtain throat swab antigen detection GAS rapid OR order test (RADT)* antigen detection If culture is test (RADT)* negative: If culture is AND No antibiotics negative: consider supportive No antibiotics AND treatment consider supportive (antipyretic OR treatment analgesic) (antipyretic OR analgesic)

Conjunctivitis Coryza Viral Pharyngitis Conjunctivitis Cough Coryza Diarrhea Cough Hoarseness Diarrhea Discrete ulcerative Hoarseness stomatitis Discrete ulcerative Viral exanthema stomatitis GAS= Group A β-hemolytic Streptococci; H= hour(s); PO= by mouth; Q= every; RADT= Rapid antigen detection test • Viral exanthema GAS= Group β-hemolytic Streptococci; hour(s); PO= by70-90%, mouth; specificity Q= every; 95% RADT= Rapid antigen detection test *Throat swabAculture sensitivity: 90-95%;H= RADT: sensitivity *Throat swab culture sensitivity: 90-95%; RADT: sensitivity 70-90%, specificity 95%

References: 1. Shulman ST, Bisno AL, Clegg HW, et al. Clinical Practice Guidelines for the Diagnosis and Management of Group A References: Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society America. Clin Infect Dis. 2012 Nov 15;55(10):12791. 82. Shulman ST, Bisno AL, Clegg HW, et al. Clinical Practice Guidelines for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update byantibiotic the Infectious Society America. ClinBackground. Infect Dis. 2012 Novof15;55(10):12792. Cooper RJ et al. Principles of appropriate use forDiseases acute pharyngitis in adults: Annals Internal 82. Medicine. 2001;134(6):509-17. 2. Cooper RJ et al. Principles of appropriate antibiotic use for acute pharyngitis in adults: Background. Annals of Internal Medicine. 2001;134(6):509-17. PAGE 17

Respiratory RespiratoryTract: Tract:Chronic ChronicObstructive ObstructivePulmonary Disease Pulmonary Disease (COPD) Exacerbation (COPD) Exacerbation CLINICAL AND THERAPEUTIC ALGORITHM Diagnosis: Based on the clinical presentation of the patient, including complaints of an acute change of cardinal symptoms as follows:

CLINICAL SEVERITY Outpatient Uncomplicated

Does patient have: increased sputum purulence AND increased dyspnea OR increased sputum 1. Initiate therapy with: • Short-acting bronchodilators (i.e. albuterol) increased to 6 to 8 puffs Q1-2H in severe exacerbations • +/- Short-acting anticholinergics (i.e. ipratropium bromide) increased to 6 to 8 puffs Q3-4H in severe exacerbations given via nebulizer/inhaler PLUS • Corticosteroids (prednisone or equivalent PO 40 mg/day for 5 days) if admitted OR have significant shortness of breath Methylprednisolone IV Q6-12H may be used initially 2. Consider obtaining sputum culture AND treat with an antimicrobial based on clinical severity • If patient has only an acute increase in 1 cardinal symptom no antibiotic therapy is recommended

RECOMMENDED REGIMENS Select ONE of the following: • Doxycycline 100 mg PO Q12H • Amoxicillin 500 mg PO Q8H • Azithromycin 500 mg once, then 250 mg PO Q24H • SMX/TMP 1 DS tablet PO Q12H Treat for 3 to 5 days

Outpatient Complicated* OR Failure of Previous Antimicrobial Therapy Inpatient

Primary Recommendation: • Amoxicillin/clavulanate 875 mg PO Q12H Penicillin Allergy or Treatment Failure with Primary Regimen: • Moxifloxacin 400 mg PO Q24H** Treat for 3 to 5 days Primary Recommendation: • Amoxicillin/clavulanate 875 mg PO Q12H OR • Doxycycline 100 mg PO Q12H Penicillin Allergy or Treatment Failure with Primary Regimen: • Moxifloxacin 400 mg PO Q24H** Treat for 5 days

3. Manage risk factors: • Assess if patient is due for influenza vaccine • Smoking cessation counseling 4. Inpatient: If worsening clinical status OR inadequate response in 72H: re-evaluate AND obtain sputum culture AND gram stain DS= double strength; H= hour(s); IV= intravenous; PO= by mouth; Q= every; SMX/TMP= sulfamethoxazole/trimethoprim *In patient with frequent exacerbations, (> 4 in previous 12 months) severe airflow limitation, and/or exacerbations requiring mechanical ventilation, FEV1 < 50%, and/or cardiovascular disease ** Previously failed therapy with azithromycin, doxycycline, and a beta- lactam OR received treatment with the aforementioned antibiotics within the previous 90 days OR patient has other comorbidities (i.e. chronic heart, liver, or renal disease, diabetes, alcoholism, malignancy, asplenia, immunocompromised or on immunosuppressing drugs. An FDA advisory committee determined that the risks of fluoroquinolone use in COPD exacerbation outweighed any potential benefit, and should not be a first-line agent. NOTE: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function References: 1. Vollenweider DJ, et al. Antibiotics for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2012 Dec 12;12:CD010257. 2. Vestbo J, et al. Global strategy for the diagnosis, manageent, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65. 3. Food and Drug Administration. Joint meeting of the Antimicrobial Drugs Advisory Committee and the Drug Safety & Risk Management Advisory Committee (DSaRM)-Webcast Recording. 2015.

PAGE 18

Rapid Respiratory Pathogen Panel (RPP) Rapid Respiratory Pathogen Panel (RPP) BioFire® Film Array Respiratory Panel rapidly (~2hours) identifies 20 target organisms via polymerase chain reaction (PCR). The table below lists all the organisms and provides interpretation guidance.

RPP Result

Definitive Therapy

Comments

Influenza A** Influenza A subtype H1** Influenza A subtype H3** Influenza A subtype H12009** Influenza B**

Reasonable to discontinue antibiotic therapy, and treat with: First line: Oseltamivir 75mg PO twice daily x5 days when CrCl ≥60mL/min See comments for renal dose adjustment→

Oseltamivir Renal Dosing: • CrCl 30-60mL/min: 30mg PO twice daily x5 days • CrCl 10-30mL/min:30mg PO once daily x5 days • Hemodialysis (HD): administer 30mg after each dialysis session for 5-day course.

Alternatives: Zanamivir 2puffs (5mg each) inhaled twice daily for 5 days Peramivir 600 mg IV single dose Refer to influenza guideline in guidebook for further drug information Bordetella pertussis**

Chlamydophila pneumoniae* Mycoplasma pneumoniae** Adenovirus‡ Coronavirus 229E* Coronavirus HKU1* Coronavirus NL63* Coronavirus OC43* Human metapneumovirus◊ Rhinovirus/enterovirus** Parainfluenza virus 1◊ Parainfluenza virus 2◊ Parainfluenza virus 3◊ Parainfluenza virus 4◊ Respiratory syncytial virus◊

First line: Azithromycin 500mg day 1, followed by 250mg days 2-5 Alternative if intolerance to macrolide: sulfamethoxazoletrimethoprim 1DS tab PO twice daily X14 days Azithromycin 500mg day 1, followed by 250mg days 2-5; or azithromycin 500mg x3 days Azithromycin 500mg day 1, followed by 250mg days 2-5; or azithromycin 500mg x3 days

HD dosing examples: If patient presents on an HD day, administer 30mg after dialysis session and repeat for 2 subsequent sessions (3 total doses). If patient presents on a non-HD day, administer dose immediately and repeat after 3 subsequent HD sessions (4 total doses) •

•

Although may be susceptible to amoxicillin in vitro, use of amoxicillin is not recommended due to risk of ineffective eradication If alternative treatment required, consider ID consult

•

Fluoroquinolones, tetracyclines (e.g. doxycycline 100mg twice daily) are reasonable alternatives

•

Fluoroquinolones, tetracyclines (e.g. doxycycline 100mg twice daily) are reasonable alternatives

No antimicrobials indicated Consider checking procalcitonin (PCT) level to help rule out superimposed bacterial infection. Please see PCT criteria in Guidebook

Type of isolation precautions: *Standard; **Droplet; ◊Contact; ‡Droplet and contact Abbreviations: HD, hemodialysis; ID, infectious diseases; IV, intravenous; PO, by mouth

PAGE 19

Sepsis Sepsis Administer antibiotics within FIRST HOUR of recognition of sepsis!

IV Antibiotics:

• If the patient is pregnant, contact pharmacy or Infectious Diseases for assistance regarding safety and dosage • Antibiotics should be adjusted for weight and renal function in ALL patients - Consult pharmacy or Infectious Diseases if needed for assistance in monitoring therapeutic drug level • Antibiotics should be ordered AFTER a review of previous microbiology data present in patient’s electronic medical record

• Risk Factors for MRSA, MDR GNR, and ESBL: - Hospitalization within the past year - Patient receives hemodialysis - Oozing or open wound - Past history of documented MRSA, MDR GNR, or ESBL - Patient is a nursing home resident - Patient has a catheter or line present If severe penicillin allergy/IgE mediated response, consider consulting ID.

UNKNOWN SOURCE Consider ADDING atypical and Legionella spp. coverage: Cefepime 2gm IV x1 STAT Azithromycin 500mg IV x1 STAT OR OR Levofloxacin 750mg IV x1 STAT Meropenem 2gm IV x1 STAT (OR if QTc >500ms Doxycycline 100mg IV x1 STAT) SUSPECTED SKIN SUSPECTED RESPIRATORY SOURCE SUSPECTED URINARY SOURCE INFECTIONS/NECROTIZING FASCIITIS Azithromycin 500 mg IV x1 STAT Piperacillin/tazobactam 4.5 gm IV Vancomycin IV x1 STAT: (OR if QTc >500ms then use <50kg-65: 1000mg x1 STAT Doxycycline 100mg IV x1 STAT) OR if risk factors for MDR GNR or >65-80kg: 1500mg ESBL PLUS >80->90kg: 2000mg Ceftriaxone 2 gm IV x1 STAT Meropenem 2 gm x1 STAT PLUS Clindamycin 900mg IV x1 STAT OR If risk factors for MRSA then ADD Piperacillin/tazobactam 4.5 gm IV PLUS Vancomycin IV x1 STAT: Cefepime 2gm IV x1 STAT x1 STAT <50kg-65: 1000mg OR OR if risk factors for MDR GNR or >65-80kg: 1500mg Meropenem 2gm IV x1 STAT ESBL >80->90kg: 2000mg Meropenem 2 gm x1 STAT OR Piperacillin/tazobactam 4.5gm IV If risk factors for MRSA then ADD Vancomycin IV x1 STAT: x1 STAT <50kg-65: 1000mg >65-80kg: 1500mg >80->90kg: 2000mg SUSPECTED Clostridium difficile SUSPECTED INTRA-ABDOMINAL SOURCE SUSPECTED CNS SOURCE INFECTION Acyclovir 10mg/kg IV x1 STAT Piperacillin/tazobactam 4.5 gm IV Vancomycin 500mg PO x1 STAT PLUS PLUS x1 STAT Ampicillin 2gm IV x1 STAT OR if risk factors for MDR GNR or Metronidazole 500mg IV x1 STAT PLUS ESBL Ceftriaxone 2g IV x1 STAT Meropenem 2 gm IV x1 STAT PLUS Vancomycin IV x1 STAT: <50kg-65: 1000mg >65-80kg: 1500mg >80->90kg: 2000mg PLUS Vancomycin IV x1 STAT: <50kg-65: 1000mg >65-80kg: 1500mg >80->90kg: 2000mg

ESBL= Extended Spectrum Beta-Lactamase; ID= Infectious Diseases; IV= intravenous; MDR GNR= Multi-Drug Resistant Gram-Negative Rods; MRSA= Methicillin-Resistant S. aureus; PO= By Mouth Reference: Rodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2016. Critical Care Medicine. 2017.;45:486-552.

PAGE 20

SymptomaticSexually SexuallyTransmitted Transmitted Infection Infection Screening Screening Symptomatic SYMPTOMATIC Symptoms Female

• • • • • • • • • •

Male

• • • • • • • • •

Recommended Diagnostic Testing

Vaginal itching Vaginal discharge Painful urination Increased urinary urgency Pelvic pain Pain with sexual intercourse Vaginal bleeding Genital warts Genital lesion/ulcer Pharyngitis

Penile discharge Painful urination Increased urgency Pelvic pain Swollen/tender testicles Pain with sexual intercourse Genital warts Genital lesion/ulcer Pharyngitis

Clinical and Therapeutic Considerations

Vaginal examination: 1. Observe vaginal anatomy 2. Gram stain for bacterial vaginosis 3. Vaginal swabs for PCR assay: • Gonorrhea • Chlamydia 4. Vaginal swabs for Affirm DNA • Trichomoniasis 5. HIV test 6. Syphilis (RPR screen/ titer) 7. Urinalysis 8. Pregnancy Test 9. Oropharyngeal (OP) Culture swab for GC when indicated

Promptly begin empiric treatment of Chlamydia and Gonorrhea before lab results return

Unable to perform vaginal examination: 1. Urinalysis 2. Urine for PCR assay: • Gonorrhea • Chlamydia 3. HIV test 4. Syphilis (RPR screen/titer) 5. Pregnancy Test 6. OP Culture for GC when indicated

Promptly begin empiric treatment of Chlamydia and Gonorrhea before lab results return

1. Urinalysis 2. Urine for PCR assay: • Gonorrhea • Chlamydia 3. HIV test 4. Syphilis (RPR screen/ titer) 5. OP Culture Swab or Rectal culture swab for GC when indicated

Promptly begin empiric treatment of Chlamydia and Gonorrhea before lab results return

Vaginal exam will allow visualization of vaginal anatomy Vaginal or cervical swab may be necessary for specific test kits

*HCV RNA screen for MSM who have engaged in condomless anal intercourse.

TREATMENT (DISCUSS TREATMENT OF PREGNANT WOMEN WITH ID AND OB/GYN) Gonorrhea Chlamydia

Ceftriaxone 250 mg IM AND Azithromycin 1 gm PO x 1 dose OR doxycycline 100 mg PO Q12H for 7 days Penicillin Allergy (anaphylaxis): Consult ID

HIV or Syphilis

Consult Infectious Diseases

Bacterial vaginosis

Metronidazole gel 0.75%, one full applicator (5gm) intravaginally once daily at bedtime for 5 days Alternatives: Metronidazole 500 mg PO Q12H OR clindamycin 300 mg PO Q12H for 7 days

Trichomonas vaginalis

Metronidazole 2 gm PO x 1 dose OR metronidazole 500 mg PO Q12H for 7 days

DNA= deoxyribonucleic acid; GC= gonococcus; H= hours; HCV= hepatitis C virus; HIV= human immunodeficiency virus; ID= infectious diseases; IM= intramuscular; MSM= men who have sex with men; OB/GYN= obstetrics/gynecology; OP= Oropharyngeal; PCR= Polymerase chain reaction; PO= by mouth; Q= every; RNA= ribonucleic acid; RPR= rapid plasma reagin; STI= sexually transmitted infection.

PAGE 21

Asymptomatic Asymptomatic Sexually Sexually Transmitted TransmittedInfection InfectionScreening Screening ASYMPTOMATIC Population Female

Age ≤ 25

Screening Recommendations

Frequency

Urine PCR for Chlamydia

Annually

Urine PCR for Gonorrhea

Annually

HIV test

At least once No later than age 21

Cervical Screening

Age > 25

No routine screening for STIs Screen according to risk

Pregnant

Urine PCR for Chlamydia

First trimester

Urine PCR for Gonorrhea

First trimester

HIV test

First trimester

Hepatitis B S Ag, S Ab, C Ab

First trimester

Hepatitis C Ab

First trimester

Syphilis RPR/titer

First trimester

Urine PCR for Chlamydia

Annually

Urine PCR for Gonorrhea*

Annually

Syphilis RPR/titer

Annually

Trichomoniasis

Annually

Hepatitis B S Ag, S Ab, C Ab

Baseline

Hepatitis C Ab

Yearly if high

HIV-positive

Clinical and Therapeutic Considerations Cervical screening should be performed 3 years after initiating sexual activity or no later than age 21 *Consider Syphilis RPR/titer in women with condomless sex with multiple sex partners or known partner with syphilis Consider minimum of annual screening if high risk* patient Repeat Screening (all pathogens) in 3rd trimester and at birth if patient is high risk*

*Consider rectal and pharyngeal culture swabs for GC if exposed May repeat screening every 3-6 months, as indicated by risk

risk* EPT= expedited partner treatment; Hepatitis B C Ab= Hepatitis B Core Antibody; Hepatitis B S Ab= Hepatitis B Surface Antibody; Hepatitis B S Ag= Hepatitis B Surface Antigen; Hepatitis C Ab= Hepatitis C Antibody; HIV= human immunodeficiency virus; MSM= Men who have sex with men; PCR= polymerase chain reaction; RPR= rapid plasma reagin; STI= sexually transmitted infection Test of Cure/ Retest Post Diagnosis and Treatment of Gonorrhea or Chlamydia Retest all patients after 3 months for reinfection (if 3 months not possible, within 1 year). Retest all pregnant patients a minimum of >/=3 weeks after completion of therapy. If suspect treatment failure, reinfection , or failure due to alternative regimen then repeat testing at a minimum of >/= 3weeks after completion of therapy. For pharyngeal gonorrhea– get test of cure on all patients after 14 days. Culture and susceptibilities preferred. Note: Gonnorrhea/Chlamydial PCR <3 weeks from completion of therapy are not recommended due to presence of non-viable organisms and false-positive results. STIs: Partner Treatment -Any recent sexual partner who has had contact with the infected patient within 60 days of their diagnosis should be considered for treatment. -Discuss treatment of partners or questions regarding Expedited Partner Treatment (EPT) with the Infectious Disease Service. -EPT should not be employed with MSMs (these patients should be referred for comprehensive STI testing first). *Definition of High Risk Those who have a new sex partner, >1 sex partner, a sex partner with concurrent partners, a sex partner who has a STI , inconsistent condom use in persons not in mutually monogamous relationships, illicit drug use, exchange of sex with drugs, recent sex contact outside the US.

PAGE 22

Asymptomatic Sexually Transmitted Infection Screening

Asymptomatic Asymptomatic Sexually Sexually Transmitted Infection ASYMPTOMATIC Transmitted InfectionScreening Screening Population Male

Heterosexual Population men

Male

Heterosexual men who have Men

sex with men (MSM) Men who have OR with men sex *high risk (MSM) heterosexual men OR

*high risk heterosexual men

HIV-positive men HIV-positive men

Screening ASYMPTOMATIC Frequency Clinical and Therapeutic Considerations Recommendations Clinical and Therapeutic Screening No routine screening Frequency for STIs. Screen according to *risk. Considerations Recommendations Note: All ‘Babyboomers’ (Patients born from 1945 through 1965) should be

screened for HCV No routine screening for STIs. Screen according to *risk. Note: All ‘Babyboomers’ (Patients born from 1945 through 1965)culture, should be Consider GC/Chl Urine PCR for Chlamydia Annually screened for HCVrectal and pharyngeal swabs Urine PCR for Gonorrhea Annually Consider GC/Chl culture, Urine PCR for Chlamydia Annually High as: swabs HIV test Annually rectalrisk anddefined pharyngeal - New or multiple sex Urine PCR for Gonorrhea Annually Hepatitis B S Ag, S Ab, C Ab Baseline Highpartners risk defined as: HIV test C Ab Annually Annually Hepatitis -- Inconsistent condom New or multiple sex use Hepatitis B S Ag, S Ab, C Ab Baseline Commercial sex work Syphilis (RPR screen/ titer) Annually partners -- Drug use Hepatitisexam C Abfor evidence of Annually Inconsistent condom use Genital Baseline - Commercial sex work Syphilis (RPR screen/ titer) Annually May repeat screening every ulcers or lesions concerning - Drug use 3-6 months, as indicated by Genital Baseline for HSV exam for evidence of risk May repeat screening every ulcers or lesions concerning 3-6 months, as indicated Consider GC/Chl culture, by for HSV Urine PCR for Chlamydia Annually risk rectal and pharyngeal swabs Urine PCR for Gonorrhea Annually Consider GC/Chl culture, Annually Urine PCR for screen/ Chlamydia May repeat screening swabs every Syphilis (RPR titer) Annually rectal and pharyngeal 3-6 months, as indicated by Urine PCRBfor Gonorrhea Annually Hepatitis S Ag, S Ab, C Ab Baseline risk repeat screening every May Syphilis (RPR Annually Hepatitis C Abscreen/ titer) Annually 3-6 months, as indicated by Hepatitis B S Ag, S Ab, C Ab Baseline Genital exam for evidence of Baseline risk Hepatitis C Ab concerning Annually ulcers or lesions Genital for HSV exam for evidence of ulcers or lesions concerning

Baseline

for HSV

GC/Chl= gonorrhea/chlamydia; HCV= Hepatitis C virus; Hepatitis B C Ab= Hepatitis B Core Antibody; Hepatitis B S Ab= Hepatitis B Surface Antibody; Hepatitis B S Ag= Hepatitis B Surface Antigen; Hepatitis C Ab= Hepatitis C Core Antibody; HIV= human immunodeficiency virus; HSV= Herpes simplex virus; MSM= Men who have sex with men; PCR= polymerase chain reaction; RPR= rapid plasma regain; STI = sexually transmitted infection. GC/Chl= gonorrhea/chlamydia; HCV= Hepatitis C virus; Hepatitis B C Ab= Hepatitis B Core Antibody; Hepatitis B S Ab= Hepatitis B Surface Antibody; Hepatitis B S Ag= Hepatitis B Surface Antigen; Hepatitis C Ab= Hepatitis C Core Antibody; HIV= human immunodeficiency virus; *Definition of High Risk HSV= Herpes simplex virus; MSM= Men who have sex with men; PCR= polymerase chain reaction; RPR= rapid plasma regain; STI = sexually Those whoinfection. have a new sex partner, >1 sex partner, a sex partner with concurrent partners, a sex partner who has a STI , transmitted

inconsistent condom use in persons not in mutually monogamous relationships, illicit drug use, exchange of sex with drugs, *Definition of Highoutside Risk the US. recent sex contact Those who have a new sex partner, >1 sex partner, a sex partner with concurrent partners, a sex partner who has a STI , inconsistent condom use in persons not in mutually monogamous relationships, illicit drug use, exchange of sex with drugs, recent sex contact outside the US.

References: 1. "Sexually Transmitted Diseases Treatment Guidelines, 2015." Centers for Disease Control and Prevention. Department of Health and Human Services, 17 Dec. 2010. URL: http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf. 2. "Primary, Secondary, and Early Latent Syphilis Surveillance 2007-2011." Division of Infectious Disease & Epidemiology. Rhode Island Department References: Health,Transmitted 2011. URL: http://www.health.ri.gov/data/diseases/Syphilis.pdf. 1. of "Sexually Diseases Treatment Guidelines, 2015." Centers for Disease Control and Prevention. Department of Health and Human 3. “California Transmitted Disease (STD) Screening Recommendations 2010”. California Department Of Public Health, June. 2011. URL: Services, 17Sexually Dec. 2010. URL: http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf. 2. http://www.cdph.ca.gov/pubsforms/Guidelines/Documents/CA-STD-Screening-Recommendations.pdf "Primary, Secondary, and Early Latent Syphilis Surveillance 2007-2011." Division of Infectious Disease & Epidemiology. Rhode Island Department of Health, 2011. URL: http://www.health.ri.gov/data/diseases/Syphilis.pdf. 3. “California Sexually Transmitted Disease (STD) Screening Recommendations 2010”. California Department Of Public Health, June. 2011. URL: PAGE 23 http://www.cdph.ca.gov/pubsforms/Guidelines/Documents/CA-STD-Screening-Recommendations.pdf

Asymptomatic Sexually Transmitted Infection Screening

Asymptomatic Asymptomatic Sexually Sexually Transmitted HIV testingInfection Transmitted InfectionScreening Screening Population

Frequency

HIV testing

Special Considerations

Consider frequent testing if high Special risk* Considerations Consider frequent testing if high Consider PREP if HIV+ partner All women age 13-64 Baseline All women who seek STI screening At time of STI risk* (Consult ID) Consider PREP if HIV+ partner Third trimester and at birth if high All women who seek STI screening At time of STI All pregnant women First Trimester (Consult ID) risk Third trimester and at birth if high Consider frequent testing if high All pregnant women First Trimester All men age 13-64 Baseline risk risk* Consider frequent testing if high Q3-6 months if higher risk activity All men age 13-64 Baseline MSM Annually (minimum) risk* (Consider PREP and consult ID) Q3-6 months if higher risk activity Consider PREP if HIV+ partner MSM Annually (minimum) All men who seek STI screening At time of STI (Consider PREP and consult ID) (consult ID) Consider PREP if HIV+ partner All men who seek STI screening Atdiseases; time ofMSM= STI Men who have sex with men; PREP= pre-exposure prophylaxis; Q= every; HIV= human immunodeficiency virus; ID= infectious (consult ID) RPR= rapid plasma regain; STI= sexually transmitted infection. All women age 13-64 Population

Baseline Frequency

HIV= human immunodeficiency virus; ID= infectious diseases; MSM= Men who have sex with men; PREP= pre-exposure prophylaxis; Q= every; *Definition of High Risk RPR= rapid STI=partner, sexually transmitted infection. Those whoplasma have aregain; new sex >1 sex partner, a sex partner with concurrent partners, a sex partner who has a STI , inconsistent condom use in persons not in mutually monogamous relationships, illicit drug use, exchange of sex with drugs, *Definition of Highoutside Risk the US. recent sex contact Those who have a new sex partner, >1 sex partner, a sex partner with concurrent partners, a sex partner who has a STI , inconsistent condom use in persons not in mutually monogamous relationships, illicit drug use, exchange of sex with drugs, recent sex contact outside the US.

References: 1. "Sexually Transmitted Diseases Treatment Guidelines, 2015." Centers for Disease Control and Prevention. Department of Health and Human Services, 17 Dec. 2010. URL: http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf. References: 2. "Primary, Secondary, and Early Latent Syphilis Surveillance 2007-2011." Division of Infectious Disease & Epidemiology. Rhode Island Department 1. of "Sexually Diseases Treatment Guidelines, 2015." Centers for Disease Control and Prevention. Department of Health and Human Health,Transmitted 2011. URL: http://www.health.ri.gov/data/diseases/Syphilis.pdf. Services, 17Sexually Dec. 2010. URL: http://www.cdc.gov/std/treatment/2010/STD-Treatment-2010-RR5912.pdf. 3. “California Transmitted Disease (STD) Screening Recommendations 2010”. California Department Of Public Health, June. 2011. URL: 2. http://www.cdph.ca.gov/pubsforms/Guidelines/Documents/CA-STD-Screening-Recommendations.pdf "Primary, Secondary, and Early Latent Syphilis Surveillance 2007-2011." Division of Infectious Disease & Epidemiology. Rhode Island Department of Health, 2011. URL: http://www.health.ri.gov/data/diseases/Syphilis.pdf. 3. “California Sexually Transmitted Disease (STD) Screening Recommendations 2010”. California Department Of Public Health, June. 2011. URL: PAGE 24 http://www.cdph.ca.gov/pubsforms/Guidelines/Documents/CA-STD-Screening-Recommendations.pdf

Skin and Soft Tissue Infections (SSTI) Skin and Tissue Infections (SSTI) Skin and SoftSoft Tissue Infections (SSTI) NONPURULENT NONPURULENT Necrotizing Infection/Cellulitis/Erysipelas Necrotizing Infection/Cellulitis/Erysipelas [Usually Streptococcus pyogenes (Group A Strep)] [Usually Streptococcus pyogenes (Group A Strep)]

Mild: Mild: signs No systemic Noofsystemic signs infection* of infection*

Moderate: Moderate: Systemic signs of Systemic signs of infection* infection*

Oral OralTherapy Antibiotic Antibiotic Therapy

Intravenous Intravenous Antibiotic Therapy Antibiotic Therapy

Select ONE: Select ONE: Penicillin VK Penicillin VKPO Q6H 250-500 mg 250-500 mg PO Q6H Cephalexin Cephalexin 500 mg PO Q6H 500 mg PO Q6H Dicloxacillin Dicloxacillin 250 mg PO Q6H 250 mg PO Q6H Clindamycin Clindamycin 300-450 mg PO Q6H 300-450 mg PO Q6H

Select ONE: Select ONE: Penicillin Penicillin 2-4 million units IV 2-4 million units IV Q4-6H Q4-6H Ceftriaxone Ceftriaxone 1 gm IV Q24H 1 gm IV Q24H Cefazolin Cefazolin 1 gm IV Q8H 1 gm IV Q8H Clindamycin Clindamycin 600-900 mg IV Q6H 600-900 mg IV Q6H

Severe:

(any ofSevere: the following): (any ofsigns the following): Systemic of infection*, Systemic signs oftreatment, infection*, failed antibiotic failed antibiotic treatment, immunocompromise, immunocompromise, hemodynamic instability, or hemodynamic instability, or deep infection deep infection Intravenous Antibiotic Therapy Intravenous Antibiotic Therapy Emergent Surgical Emergent Surgical Inspection/Debridement •Inspection/Debridement Rule out necrotizing • process Rule out necrotizing process Culture & Sensitivity Culture & Sensitivity Empiric Treatment Treatment •Empiric Vancomycin 15 mg/kg • IV** Vancomycin PLUS 15 mg/kg IV** PLUS • Piperacillin/tazobactam • Piperacillin/tazobactam 3.375 gm IV Q6H 3.375 gm IV Q6H +/• +/Clindamycin 900 mg IV • Q8H*** Clindamycin 900 mg IV Q8H***

Defined Treatment (Necrotizing Infections) Defined Treatment (Necrotizing Infections) Monomicrobial Monomicrobial Streptococcus pyogenes pyogenes •Streptococcus Penicillin 2-4 million units IV Q4-6H PLUS Clindamycin 600-900 mg IV Q8H • Penicillin 2-4 million units IV Q4-6H PLUS Clindamycin 600-900 mg IV Q8H Vibrio vulnificus vulnificus100 mg IV Q12H PLUS Ceftazidime 2 gm IV Q8H •Vibrio Doxycycline • Doxycycline 100 mg IV Q12H PLUS Ceftazidime 2 gm IV Q8H Aeromonas hydrophila hydrophila •Aeromonas Doxycycline 100 mg IV Q12H PLUS Ciprofloxacin 400 mg IV Q12H • Doxycycline 100 mg IV Q12H PLUS Ciprofloxacin 400 mg IV Q12H Polymicrobial •Polymicrobial Vancomycin 15 mg/kg IV** PLUS Piperacillin/tazobactam 3.375 gm IV Q4H • Vancomycin 15 mg/kg IV** PLUS Piperacillin/tazobactam 3.375 gm IV Q4H

H= hours; IV= intravenous; PO= oral; Q= every H= hours; IV= intravenous; PO= oral; Q= every *Systemic signs of infection include, but are not limited to, temperature >38°C, tachycardia (heart rate >90 beats per minute), tachypnea signs (respiratory rate >24 breaths or abnormal white blood count (>12 000 or <4000 *Systemic of infection include, but per are minute) not limited to, temperature >38°C,cell tachycardia (heart rate >90 cells/µL). beats per minute), **Refer to (respiratory section on Vancomycin Dosingper and Monitoring in Adultwhite Patients. tachypnea rate >24 breaths minute) or abnormal blood cell count (>12 000 or <4000 cells/µL). ***Consider this addition for necrotizing fasciitis. **Refer to section on Vancomycin Dosing and Monitoring in Adult Patients. Note: Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function for dosing in ***Consider this addition for necrotizing fasciitis. patients with Note: Refer torenal Tableimpairment. of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function for dosing in patients with renal impairment. References: 1. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin References: and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014; 59(2): e10-52. 1. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJ, Gorbach SL, et al. Practice guidelines for the diagnosis and management of skin 2. Duong M, Markwell S, Peter J, Barenkamp S. Randomized, controlled trial of antibiotics in the management of community-acquired skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014; 59(2): e10-52. abscesses in the pediatric patient. Ann Emerg Med 2010; 55:401–7. 2. Duong M, Markwell S, Peter J, Barenkamp S. Randomized, controlled trial of antibiotics in the management of community-acquired skin 3. Macfie J, Harvey J. The treatment of acute superficial abscesses: a prospective clinical trial. Br J Surg 1977; 64:264–6. abscesses in the pediatric patient. Ann Emerg Med 2010; 55:401–7. 4. Llera JL, Levy RC. Treatment of cutaneous abscess: a double-blind clinical study. Ann Emerg Med 1985; 14:15–9. 3. Macfie J, Harvey J. The treatment of acute superficial abscesses: a prospective clinical trial. Br J Surg 1977; 64:264–6. 5. Rutherford WH, Hart D, Calderwood JW, Merrett JD. Antibiotics in surgical treatment of septic lesions. Lancet 1970; 1:1077–80. 4. Llera JL, Levy RC. Treatment of cutaneous abscess: a double-blind clinical study. Ann Emerg Med 1985; 14:15–9. 6. Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in 5. Rutherford WH, Hart D, Calderwood JW, Merrett JD. Antibiotics in surgical treatment of septic lesions. Lancet 1970; 1:1077–80. patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection. Ann Emerg Med 2010; 56:283–7. 6. Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection. Ann Emerg Med 2010; 56:283–7.

PAGE 25

Skin and Tissue Infections (SSTI) Skin and SoftSoft Tissue Infections (SSTI) PURULENT Furuncle/Carbuncle/Abscess (Usually Staphylococcus aureus) Mild: No systemic signs of infection*

Moderate: Systemic signs of infection*

No Antibiotic Therapy

Incision and Drainage and C&S

Incision and Drainage

Oral Antibiotic Therapy

Severe:

(any of the following): Failed I&D and oral antibiotics, systemic signs of infection*, immunocompromise, hemodynamic instability, or deep infection

Incision and Drainage and C&S

Empiric Therapy (select ONE): • TMP/SMX 1-2 DS tablets PO Q12H • Doxycycline 100 mg PO Q12H Defined Therapy MRSA • TMP/SMX (see empiric dose) MSSA (select ONE): • Dicloxacillin 500 mg PO Q6H • Cephalexin 500 mg PO Q6H

Intravenous Antibiotic Therapy

Empiric Therapy (select ONE): • Vancomycin 15 mg/kg IV** • Daptomycin 6 mg/kg IV Q24H • Linezolid 600 mg IV Q12H • Ceftaroline 600 mg IV Q12H Defined Therapy MRSA • See empiric therapy above MSSA (select ONE): • Nafcillin 1-2 gm IV Q4H • Cefazolin 1 gm IV Q8H • Clindamycin 600 mg IV Q8H C&S= culture and sensitivity; DS= double-strength; H= Hours; I&D= incision and drainage; IV= intravenous; MRSA= methicillinresistant Staphylococcus aureus; MSSA= methicillin-susceptible Staphylococcus aureus; PO= by mouth; Q= every; Rx= treatment; TMP/SMX= trimethoprim-sulfamethoxazole *Systemic signs of infection, but are not limited to, include temperature >38°C, tachycardia (heart rate >90 beats per minute), tachypnea (respiratory rate >24 breaths per minute) or abnormal white blood cell count (>12 000 or <4000 cells/µL). **Refer to section on Vancomycin Dosing and Monitoring in Adult Patients. References: 1. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014; 59(2): e10-52. 2. Duong M, Markwell S, Peter J, Barenkamp S. Randomized, controlled trial of antibiotics in the management of community-acquired skin abscesses in the pediatric patient. Ann Emerg Med 2010; 55:401–7. 3. Macfie J, Harvey J. The treatment of acute superficial abscesses: a prospective clinical trial. Br J Surg 1977; 64:264–6. 4. Llera JL, Levy RC. Treatment of cutaneous abscess: a double-blind clinical study. Ann Emerg Med 1985; 14:15–9. 5. Rutherford WH, Hart D, Calderwood JW, Merrett JD. Antibiotics in surgical treatment of septic lesions. Lancet 1970; 1:1077–80. 6. Schmitz GR, Bruner D, Pitotti R, et al. Randomized controlled trial of trimethoprim-sulfamethoxazole for uncomplicated skin abscesses in patients at risk for community-associated methicillin-resistant Staphylococcus aureus infection. Ann Emerg Med 2010; 56:283–7.

PAGE 26

Skin Skinand andSoft SoftTissue: Tissue:Diabetic DiabeticFoot FootInfections Infections SEVERITY OF INFECTION Mild • Only skin and subcutaneous tissue involvement AND • Erythema > 0.5 cm and ≤ 2 cm around ulcer • Perform incision and drainage as necessary

Moderate** • Deeper tissue involvement OR • Erythema > 2.0 cm around ulcer AND • No systemic signs of infection • Perform incision and drainage as necessary

SUSPECTED ORGANISMS

RECOMMENDED EMPIRICAL TREATMENT

DURATION

MSSA Streptococcus spp.

Oral Amoxicillin/clavulanate 875 mg PO Q12H OR Cephalexin 500 mg PO Q6H OR Dicloxacillin 250 – 500 mg PO Q6H

MRSA

Doxycycline 100 mg PO Q12H OR SMX/TMP 2 DS tablets PO Q12H (Does not cover Group A Strep) Oral OR Initially Parenteral 1–3 weeks Ampicillin-sulbactam 1.5–3 gm IV Q6H OR Ceftriaxone 1 gm IV Q24H

MSSA Streptococcus spp. Enterobacteriaceae Obligate anaerobes

1–2 weeks

Penicillin Allergy:

MRSA

Pseudomonas aeruginosa

Ciprofloxacin 500 mg PO Q12H AND Clindamycin 300 mg PO Q6H OR Ceftriaxone 1 gm IV Q24H Linezolid 600 mg IV/PO Q12H† (Requires ID Consult) OR Daptomycin 6 mg/kg IV Q24H† (Requires ID Consult) OR Vancomycin 15 mg/kg IV* Piperacillin-tazobactam 3.375 gm IV Q4H

DS= Double Strength; H= hour(s); IV= intravenous; MRSA= methicillin resistant S. aureus; MSSA= methicillin sensitive S. aureus; PO= by mouth; Q= every; SMX-TMP= sulfamethoxazole/trimethoprim; spp= species † Restricted Antibiotic – refer to Table of Contents for Guidelines for Restricted Antimicrobials * Refer to Table of Contents for section on Vancomycin Dosing and Monitoring in Adult Patients ** Consult Infectious Diseases and Podiatry NOTE: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function

PAGE 27

Skin and Soft Tissue: Diabetic Foot Infections

R Infections E Skin Skin andI SoftTissue: Tissue: Diabetic Foot Infections Foot S and Soft S Diabetic O EVERITY OF NFECTION

Severe** SEVERITY OF INFECTION • Same as moderate AND Severe** •• Systemic signs of infection Same as moderate present AND Systemic Inflammatory • Systemic signs of infection Response presentSyndrome (SIRS) Criteria of the following: Systemic≥2Inflammatory Response Syndrome (SIRS) • Temperature <96.8°F Criteria ≥2 of the following: OR >100.4°F •• P > 90 BPM <96.8°F Temperature • OR RR >>100.4°F 20 BPM < 32 mmHg PaCO •• P > 902 BPM •• WBC < 4000 RR > 20 BPMcells/mm³ cells/mm³ • OR PaCO>12,000 2 < 32 mmHg ≥ 10%<immature (band) •• WBC 4000 cells/mm³ forms >12,000 cells/mm³ OR incision and •• ≥Perform 10% immature (band) drainage as necessary forms

USPECTED

RGANISMS

MSSA/MRSA SUSPECTED ORGANISMS P. aeruginosa Streptococcus MSSA/MRSA spp. Enterobacteriaceae P. aeruginosa Obligate anaerobes Streptococcus spp. Enterobacteriaceae Obligate anaerobes

ECOMMENDED MPIRICAL TREATMENT

DURATION

Initially ParenteralEMPIRICAL RECOMMENDED DURATION TREATMENT Vancomycin 15 mg/kg IV* Initially AND** Parenteral 2–4 weeks Cefepime 2 gm Q8H IV* + Vancomycin 15 IV mg/kg metronidazole 500 mg IV Q6H AND** 2–4 weeks OR Cefepime 2 gm IV Q8H + Piperacillin-tazobactam metronidazole 500 mg IV Q6H 3.375 gm IV Q4H OR Piperacillin-tazobactam Bone OR Involvement‡ 3.375 gm Joint IV Q4H

Source removed: 2-5 days Bone OR Joint Involvement‡ Source removed but residual tissue infection: Source removed: 2-5 days 1-3 weeks Source removed but residual tissue infection: bone infection: 1-3 4-6 weeks Source removed but residual bone infection: not removed: ≥3 months 4-6 weeks

BPM= beats orincision breaths per methicillin S. aureus; MSSA= methicillin • Perform andminute; H= hour(s); IV= intravenous; MRSA=Source notresistant removed: ≥3 months sensitive S. aureus; P= pulse; PaCO2= partial pressure of carbon dioxide; Q= every; RR= respiratory rate; SIRS= Systemic drainage as necessary Inflammatory Response Syndrome; spp= species; WBC= white blood cell BPM= beats or breaths per minute; H= hour(s); IV= intravenous; MRSA= methicillin resistant S. aureus; MSSA= methicillin † Restricted Antibiotic – referPaCO2= to Tablepartial of Contents forofGuidelines for Restricted sensitive S. aureus; P= pulse; pressure carbon dioxide; Q= every;Antimicrobials RR= respiratory rate; SIRS= Systemic * Refer to Table of Contents for section Vancomycin Dosingblood and Monitoring in Adult Patients Inflammatory Response Syndrome; spp=on species; WBC= white cell ** Consult Infectious Diseases and Podiatry Antibiotic – refer to Table ofPodiatry, Contentsand for Vascular Guidelines for Restricted Antimicrobials ‡† Restricted Discuss plan with Infectious Diseases, * Refer to Table of Contents for section on Vancomycin Dosing and Monitoring in Adult Patients ** Consult Infectious Diseases Podiatry NOTE: Dosing based on normaland renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult ‡Patients DiscussBased plan with Infectious Diseases, Podiatry, and Vascular on Renal Function NOTE: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function

References: 1. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis 2012;54(12):e132-73. 2. Flagyl [package insert]. New York, NY: Pfizer; 2015. References:

1. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis 2012;54(12):e132-73. PAGE 28 2. Flagyl [package insert]. New York, NY: Pfizer; 2015.

Surgical Decolonization and Prophylaxis Surgical Decolonization and Prophylaxis Dand ECOLONIZATION Surgical Decolonization Prophylaxis Nasal Screening Result MRSA Negative Result Nasal Screening MSSA Negative MRSA Negative MRSA Positive MSSA Negative MRSA Positive

DRecommended ECOLONIZATION Intervention • No decolonization required Recommended Intervention • No decolonization required • Intranasal mupirocin twice daily x 5 days, AND •• Intranasal mupirocin dailyprior x 5 days, Chlorhexidine bathingtwice one day to surgery AND ANTIMICROBIAL PROPHYLAXIS • Chlorhexidine bathing one day prior to surgery LINICAL CONSIDERATIONS AC NTIMICROBIAL PROPHYLAXIS

• Preoperative dose-timing CLINICAL CONSIDERATIONS Within 60 minutes of surgical incision • Preoperative Exceptions:dose-timing vancomycin and fluoroquinolones within 120 minutes of surgical Within incision60 minutes of surgical incision Exceptions: vancomycin and fluoroquinolones within 120 minutes of surgical • Weight-based dosing incision Cefazolin: 2 gm for patients <120 kg, and 3 gm for patients ≥120 kg • Weight-based Vancomycin:dosing use ABW Cefazolin: 2 gm patients and 3 gm for patients Gentamicin: usefor ABW unless<120 ABWkg, is >120% of their IBW, in≥120 whichkgcase use Vancomycin: use ABW AdjBW (see below for equation) Gentamicin: use ABW unless ABW is >120% of their IBW, in which case use • Duration of prophylaxis AdjBW below for equation) A single(see dose, or continuation for <24 hours is recommended • Duration of prophylaxis -OPERATIVE A single dose, or continuationINTRA for <24 hours isREDOSING recommended • Required if the duration of procedure exceeds two half-lives of the drug or if there INTRA-OPERATIVE REDOSING is extensive blood loss during the procedure (>1500 mL) Ŧ • Required if the duration of same procedure exceeds theredosing drug or ifinterval there Recommendation: use the antibiotic dosetwo andhalf-lives measureofthe is extensive blood loss during theofprocedure (>1500 dose, mL) Ŧ not the time of incision from the time of administration the preoperative •ABW= Recommendation: use the same antibiotic dose and measure the redosing interval actual body weight; AdjBW= adjusted body weight; IBW= ideal body weight; MRSA= Methicillin-resistant Staphylococcus from theMethicillin-susceptible time of administration ofaureus the preoperative dose, not the time of incision aureus; MSSA= Staphylococcus ABW= actual body AdjBW= IBW= ideal body MRSA= Methicillin-resistant Staphylococcus Ŧ Redosing may notweight; be necessary foradjusted patientsbody withweight; poor renal function (CrClweight; <30mL/min) aureus; MSSA= Methicillin-susceptible Staphylococcus aureus

IBW Calculation: AdjBW Calculation: Ŧ Redosing may not be necessary for patients with poor renal function (CrCl <30mL/min) Male = 50 kg + [2.3 kg for each inch over 5 feet] AdjBW = 0.4 (ABW-IBW) + IBW Female = 45 kg + [2.3 kg for each inch over 5 feet] IBW Calculation: AdjBW Calculation: Male = 50 kg + [2.3 kg for each inch over 5 feet] Female = 45 kg + [2.3 kg for each inch over 5 feet]

AdjBW = 0.4 (ABW-IBW) + IBW

References: 1. Schweuzer ML, Chiang H, Septimus E, Moody J, Braun B, Hafner J, et al. Association of a Bundled Intervention with Surgical Site Infections Among Patients Undergoing Cardiac, Hip, or Knee Surgery (STOP SSI – Study to Optimally Prevent SSI in Select Cardiac and Orthopedic Procedures). JAMA 2015; 313(21): 2162-2171. References: 2. Chen AF, Wessel CB, Rao Staphylococcus Screening and Decolonization in of Orthopaedic Surgery and Reduction of Surgical Site 1. Schweuzer ML, Chiang H, N. Septimus E, Moodyaureus J, Braun B, Hafner J, et al. Association a Bundled Intervention with Surgical Site Infections Infections. Clin Orthop Relat Cardiac, Res 2013;Hip, 471: Among Patients Undergoing or2383-2399. Knee Surgery (STOP SSI – Study to Optimally Prevent SSI in Select Cardiac and Orthopedic 3. Bratzler DW, Dellinger EP,313(21): Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in Procedures). JAMA 2015; 2162-2171. surgery. J Health Syst N. Pharm 2013; 70:195-283. 2. Chen AF,Am Wessel CB, Rao Staphylococcus aureus Screening and Decolonization in Orthopaedic Surgery and Reduction of Surgical Site Infections. Clin Orthop Relat Res 2013; 471: 2383-2399. 3. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis PAGE in29 surgery. Am J Health Syst Pharm 2013; 70:195-283.

Antimicrobial Surgical Prophylaxis

â&#x20AC;&#x201A;Antimicrobial Surgical Prophylaxis Antimicrobial Surgical R Prophylaxis R EDOSING

REDOSING ECOMMENDATIONS Half-life R (hours)

Antibiotic Ampicillin/sulbactam Antibiotic

ECOMMENDATIONS

0.8-1.3

Half-life (hours)

Cefazolin 1.2-2.2 Ampicillin/sulbactam 0.8-1.3 Cefoxitin 0.7-1.1 Cefazolin 1.2-2.2 Ciprofloxacin 3-7 Cefoxitin 0.7-1.1 Clindamycin 2-4 Ciprofloxacin 3-7 Gentamicin 2-3 Clindamycin 2-4 Metronidazole 6-8 Gentamicin 2-3 Vancomycin 4-8 Metronidazole 6-8 SURGICAL R ECOMMENDED AGENTS Vancomycin 4-8 PROCEDURE S URGICAL Laparoscopic, None RECOMMENDED AGENTS PROCEDURE

low-risk Laparoscopic, Laparoscopic, low-risk high-risk Laparoscopic, high-risk Small intestine, nonobstructed Small intestine, Small intestine, nonobstructed obstructed Small intestine, Hernia repair obstructed Hernia repair Colorectal Colorectal

Head and neck, clean Head and neck, Head and neck, clean placement of Head and neck, prosthetic placement of Cleanprosthetic contaminated Cleancancer surgery contaminated cancer surgery

None Cefazolin, cefoxitin, cefotetan, ceftriaxone, Cefazolin, cefoxitin, ampicillin/sulbactam cefotetan, ceftriaxone, Cefazolin ampicillin/sulbactam Cefazolin Cefazolin + metronidazole, cefoxitin, cefotetan Cefazolin + metronidazole, Cefazolin cefoxitin, cefotetan

Redosing Interval (hours) 2

Redosing Interval (hours)

4 2 2 4 Not necessary 2 6 Not necessary Not necessary 6 Not necessary Not necessary Not necessary Not necessary ALTERNATIVES FOR PATIENTS WITH BETA-LACTAM Not necessary ALLERGY ALTERNATIVES FOR PATIENTS WITH BETA-LACTAM None ALLERGY

None Clindamycin or vancomycin + aminoglycoside or aztreonam or fluoroquinolone Clindamycin or vancomycin + aminoglycoside or aztreonam or fluoroquinolone Clindamycin + aminoglycoside or aztreonam or fluroquinolone Clindamycin + aminoglycoside or Metronidazole + aminoglycoside or aztreonam or fluroquinolone fluoroquinolone Metronidazole + aminoglycoside or Clindamycin, vancomycin fluoroquinolone

Cefazolin + metronidazole, cefoxitin, cefotetan, Cefazolin + metronidazole, ampicillin/sulbactam, cefoxitin, cefotetan, ceftriaxone + ampicillin/sulbactam, metronidazole, ertapenem ceftriaxone + None metronidazole, ertapenem

Clindamycin, Clindamycin +vancomycin aminoglycoside or aztreonam or fluroquinolone; Clindamycin + aminoglycoside or or Metronidazole + aminoglycoside aztreonam or fluroquinolone; fluoroquinolone Metronidazole + aminoglycoside or fluoroquinolone None

None Cefazolin, cefuroxime

None Clindamycin

Cefazolin, cefuroxime

Clindamycin

Cefazolin + metronidazole, cefuroxime + Cefazolin + metronidazole, metronidazole, cefuroxime + ampicillin/sulbactam metronidazole, ampicillin/sulbactam

Clindamycin Clindamycin

References: 1. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70:195-283. References: 1. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in PAGE 30 surgery. Am J Health Syst Pharm 2013; 70:195-283.

Antimicrobial Surgical Prophylaxis Antimicrobial Surgical Prophylaxis Antimicrobial Surgical Prophylaxis ALTERNATIVES FOR PATIENTS WITH SURGICAL PROCEDURE RECOMMENDED AGENTS SURGICAL Ortho: cleanPROCEDURE hand, knee, or foot not Ortho: clean hand, involving implantation knee, or foot not of foreign materials involving implantation Ortho: implantation of foreign materials of foreign material and/or Ortho: implantation of total joints foreign material and/or Urologic with risk total joints factors for infection Urologic with risk Urologic, clean without factors for infection entry into urinary tract Urologic, clean without Urologic involving entry into urinary tract implanted prosthesis Urologic involving implanted prosthesis

RECOMMENDED AGENTS None

BETA-LACTAM ALLERGY ALTERNATIVES FOR PATIENTS WITH None BETA-LACTAM ALLERGY

None

Cefazolin

Clindamycin, vancomycin

Cefazolin

Clindamycin, vancomycin

Fluoroquinolone, TMP/SMX, cefazolin Fluoroquinolone, Cefazolin* TMP/SMX, cefazolin

Aminoglycoside +/- clindamycin

Cefazolin* Cefazolin ± aminoglycoside, Cefazolin cefazolin ±± aztreonam, aminoglycoside, ampicillin/sulbactam cefazolin ± aztreonam, Cefazolin* ampicillin/sulbactam

Clindamycin, vancomycin Clindamycin ± aminoglycoside or aztreonam, vancomycin ± Clindamycin ± aminoglycoside aminoglycoside or aztreonam or aztreonam, vancomycin ± aminoglycoside or aztreonam Fluoroquinolone, aminoglycoside ± clindamycin Fluoroquinolone, aminoglycoside ± Fluoroquinolone, aminoglycoside + clindamycin metronidazole or clindamycin Fluoroquinolone, aminoglycoside + metronidazole or clindamycin

Urologic, clean with entry into urinary tract Urologic, clean with Cefazolin* Urologic, Cefazolin + entry intocleanurinary tract contaminated metronidazole, cefoxitin Urologic, cleanCefazolin + TMP/SMX= trimethoprim/sulfamethoxazole contaminated metronidazole, cefoxitin

Aminoglycoside +/- clindamycin Clindamycin, vancomycin

*Addition of a single dose of an aminoglycoside may be recommended for placement of prosthetic material (e.g. penile TMP/SMX= prosthesis) trimethoprim/sulfamethoxazole *Addition of a single dose of an aminoglycoside may be recommended for placement of prosthetic material (e.g. penile prosthesis)

References: 1. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70:195-283. References: 1. Bratzler DW, Dellinger EP, Olsen KM, Perl TM, Auwaerter PG, Bolon MK, et al. Clinical practice guidelines for antimicrobial prophylaxis in PAGE 31 surgery. Am J Health Syst Pharm 2013; 70:195-283.

Urinary UrinaryTract: Tract: Catheter-Associated Catheter-Associated Urinary Tract Infection Urinary Tract Infection CLASSIFICATION Asymptomatic Bacteriuria

CLINICAL FINDINGS • Positive urine culture (≥ 100,000 cfu/mL of ≥ 1 bacterial species in a single catheter urine specimen) AND • No sign or symptoms

Remove catheter No antibiotics unless the patient is: • Scheduled for urologic procedure • Pregnant Scheduled Urologic Procedure: SMX/TMP 1 DS tablet PO Q12H OR Ciprofloxacin 500 mg PO OR Ciprofloxacin 400 mg IV Q12H Initiate within 24 hours prior to procedure and until foley removed Pregnant: Amoxicillin 500 mg PO Q8H for 3 to 7 days OR Cephalexin 500 mg PO Q6H for 3 to 7 days OR Nitrofurantoin (MacroBID)‡ 100 mg PO Q12H for 5 days

Symptomatic

• Positive urine culture (≥ 1,000 cfu/mL of ≥ 1 bacterial species in a single catheter urine specimen) AND • Presence of signs/symptoms Catheter still in place: - Malaise/lethargy - Fever (≥100.4°F)/rigors - Altered mental status - Flank pain - Pelvic discomfort - Acute hematuria Catheter removed within past 48 h: - Dysuria - Urgency - Frequency - Suprapubic pain/tenderness

CLINICAL CONSIDERATIONS

RECOMMENDED EMPIRIC REGIMENS

Outpatient: SMX/TMP DS tablet PO Q12H OR Nitrofurantoin (MacroBID)‡ 100 mg PO Q12H OR Ciprofloxacin 250 - 500 mg PO Q12H Inpatient: Cefazolin 2 gm IV Q8H OR Cefepime 1 gm IV Q12H OR Ampicillin/sulbactam 1.5 gm IV Q6H Known or suspected ESBL bacteria: Meropenem 1 gm IV Q8H OR Ertapenem 1 gm IV Q24H

•

• •

•

Obtaining routine cultures in asymptomatic patients is NOT recommended In the presence of a catheter, pyuria (>5-10 WBC) in an asymptomatic patient is NOT an indication for antibiotic treatment Presence or absence of odorous or cloudy urine alone is NOT an indication for antibiotic treatment Antibiotics do NOT decrease asymptomatic bacteriuria or prevent subsequent UTI Remove catheter whenever possible Narrow antibiotic therapy when organism and susceptibilities are known Follow-up urine cultures or urinalysis are only warranted for ongoing symptoms. They should NOT be obtained routinely to monitor response to therapy

Duration of Treatment: Prompt resolution: 7 days Delay response: 10-14 days

cfu= colony forming units; DS= double strength; ESBL= extended spectrum beta-lactamase; H= hour(s); IV= intravenous; MDRO= multi-drug resistant organism; PO= by mouth; Q= every; SMX/TMP= sulfamethoxazole/trimethoprim; UTI= Urinary Tract Infection; WBC= white blood cell ‡Nitrofurantoin: Contraindicated if CrCl< 60 mL/min AND only indicated in acute cystitis

PAGE 32

Urinary Urinary Tract: Non-Catheter Associated Tract: Non-Catheter Associated Urinary Tract Infection/Cystitis Urinary Tract Infection CLASSIFICATION Asymptomatic Bacteriuria

CLINICAL FINDINGS • Pyuria (urinalysis > 5- 10 WBC) OR • Positive urine culture (≥ 100,000 cfu/mL)† AND • No sign or symptoms (see below)

RECOMMENDED EMPIRIC REGIMENS

No antibiotics unless the patient is: • Scheduled for urologic procedure • Pregnant Scheduled Urologic Procedure: SMX/TMP 1 DS tablet PO Q12H OR Ciprofloxacin 500 mg PO OR Ciprofloxacin 400 mg IV Q12H

CLINICAL CONSIDERATIONS

•

Obtaining routine cultures in asymptomatic patients is NOT recommended Antibiotics do NOT decrease asymptomatic bacteriuria or prevent subsequent UTI

Initiate within 24 hours prior to procedure and until foley removed Pregnant: Amoxicillin 500 mg PO Q8H for 3 to 7 days OR Cephalexin 500 mg PO Q6H for 3 to 7 days OR Nitrofurantoin (MacroBID)‡ 100 mg PO Q12H for 5 days Symptomatic: Complicated ≥ 1 of the following: • Male • Pyelonephritis • Antibiotic use in previous 90 days • History of infection with MDRO • Immunocompromised • Functional or anatomic urologic abnormality • Severe sepsis

• Pyuria (Urinalysis ≥ 5 WBC) AND • Positive urine culture (≥ 100,000 cfu/mL)† AND • Presence of symptoms: - Dysuria - Urgency - Frequency - Suprapubic pain AND/OR • Presence of signs: - Fever (≥ 100.4°F) - Altered mental status - Leukocytosis

Outpatient: SMX/TMP 1 DS tablet PO Q12H OR Nitrofurantoin (MacroBID)‡ 100 mg PO Q12H OR Ciprofloxacin 250 - 500 mg PO Q12H Inpatient: Cefazolin 2 gm IV Q8H OR Cefepime 1 gm IV Q12H OR Ceftriaxone 1 gm IV Q24H OR Ampicillin/sulbactam 1.5 gm IV Q6H

•

Narrow antibiotic therapy when organism and susceptibilities are known Follow-up urine cultures or urinalysis are only warranted for ongoing symptoms. They should NOT be obtained routinely to monitor response to therapy

Known or suspected ESBL bacteria: Meropenem 1 gm IV Q8H OR Ertapenem 1 gm IV Q24H Duration of Treatment: 7 to 14 days

cfu= colony forming units; ESBL= extended spectrum beta-lactamase; H= hour(s); IV= intravenous; MDRO= multi-drug resistant organism; PO= by mouth; Q= every; SMX/TMP= sulfamethoxazole/trimethoprim; UTI= Urinary Tract Infection; WBC= white blood cell count †Positive urine culture: For Women: 2 consecutive voided urine specimens with isolation of >105 cfu/mL of the same bacterial strain For Men: A single, clean-catch, voided urine specimen with isolation of >105 cfu/mL from 1 bacterial species ‡Nitrofurantoin: Contraindicated if CrCl< 60 mL/min AND only indicated in acute cystitis NOTE: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function

PAGE 33

Tract: Non-Catheter Associated Urinary Tract Urinary Urinary Tract: Non-Catheter Associated Urinary Tract: Non-Catheter Associated Urinary Tract Infection/Cystitis Tract: Non-Catheter Associated Urinary Tract Urinary Urinary Tract Infection/Cystitis Infection/Cystitis CLASSIFICATION CLINICAL FINDINGS Infection/Cystitis CLASSIFICATION CLINICAL FINDINGS Symptomatic CLASSIFICATION Uncomplicated/ Symptomatic Cystitis Uncomplicated/ Symptomatic • Female Cystitis Uncomplicated/ •ANDFemale Cystitis No criteria for AND •• Female complicated • No criteria for AND previous complicated • (see No criteria for page) (see previous complicated page) (see previous page)

• CPyuria LINICAL FINDINGS ≥5 • (Urinalysis: Pyuria WBC) ≥5 • (Urinalysis: Pyuria AND WBC) (Urinalysis: ≥ 5 • WBC) Positive urine AND 100,000 • culture Positive(≥urine AND † cfu/mL) culture (≥ 100,000 • Positive urine † AND cfu/mL)(≥ 100,000 culture † of • cfu/mL) Presence AND symptoms: • Presence of AND - Dysuria • symptoms: Presence of Urgency - Dysuria symptoms: Frequency Urgency -- Dysuria Suprapubic - Frequency Urgency pain - Suprapubic Frequency - pain Suprapubic pain

RECOMMENDED EMPIRIC REGIMENS RECOMMENDED EMPIRIC REGIMENS Nitrofurantoin (MacroBID) RECOMMENDED EMPIRIC R‡ EGIMENS

100 mg PO Q12H for 5 days‡ Nitrofurantoin (MacroBID) OR mg PO Q12H 100 for 5 days‡ Nitrofurantoin (MacroBID) SMX/TMP DS tablet Q12H for OR 100 mg PO1Q12H for 5PO days 3 days SMX/TMP 1 DS tablet PO Q12H for OR 3 days SMX/TMP DS tablet PO Q12H for Alternative1agents should be avoided 3 if days possible due to the risk ofbeC.avoided difficile Alternative agents should

AND antibiotic resistance. IFC.avoided patient if possible due to the risk ofbe difficile Alternative agents should has an allergy/contraindication to the antibiotic resistance. AND if possible due to the risk ofIFC.patient difficile above antibiotics alternatives include: has allergy/contraindication to the ANDan antibiotic resistance. IF patient Ciprofloxacin 250 alternatives mg PO Q12Hinclude: for 3 above has anantibiotics allergy/contraindication to the days Cephalexin POinclude: Q12H Ciprofloxacin 250 alternatives mg500 POmg Q12H for 3 aboveOR antibiotics for 3 OR daysCephalexin PO for Q12H days Ciprofloxacin 250 mg500 POmg Q12H 3 for daysCephalexin 500 mg PO Q12H days3 OR for 3 days

Urinary Tract: Prostatitis Tract: Prostatitis Urinary Urinary Tract: Prostatitis Urinary Tract: Prostatitis CLASSIFICATION PREFERRED REGIMEN ALTERNATIVE REGIMENS CLASSIFICATION Outpatient CLASSIFICATION Outpatient Outpatient

PREFERRED REGIMEN Ciprofloxacin mg PO PREFERRED500 REGIMEN

Q12H Ciprofloxacin 500 mg PO Q12H Ciprofloxacin 500 mg PO Q12H

ALTERNATIVE REGIMENS SMX/TMP 1 DS tabletRPO Q12H ALTERNATIVE EGIMENS

OR SMX/TMP 1 DS tablet PO Q12H Levofloxacin 500 mg PO OR SMX/TMP 1 DS tablet POonce Q12Hdaily (Requires ID Consult) Levofloxacin 500 mg PO once daily OR (Requires ID Consult) Levofloxacin 500 mg PO 28 once daily Duration of Treatment: days (Requires ID Treatment: Consult) 28 days Duration of

CLINICAL CLINICAL CONSIDERATIONS CONSIDERATIONS CLINICAL • Urine culture Cshould ONSIDERATIONS be

• •

• • • • • •

Urine culture performed should be ONLY IF: Urine culture - History performed ONLY IF: should be of multipleof UTIs IF: - History performed ONLY OR MDRO - multiple History ofUTIs infection(s) OR MDRO multiple UTIs Narrow antibiotic infection(s) OR MDRO therapy when Narrow antibiotic infection(s) organismantibiotic and therapy when Narrow susceptibilities organism and are therapy when known and are susceptibilities organism Follow-up urineare known susceptibilities cultures UA are Follow-up known orurine only warranted for cultures orurine UA are Follow-up on-going only warranted for cultures or UA are symptoms. Theyfor on-going only warranted should NOTThey be symptoms. on-going obtained routinely should NOT be symptoms. They to monitor obtained routinely should NOT be response to to monitorroutinely obtained therapy response to to monitor therapy response to therapy

CLINICAL CLINICAL CONSIDERATIONS CONSIDERATIONS CLINICAL Beta-lactams DO NOT ONSIDERATIONS haveCadequate Beta-lactams DO NOT

penetration into have adequate Beta-lactams DO prostate NOT penetration into prostate have adequate penetration into prostate

cfu= colony forming units; DS= double strength; H= hour(s); MDRO= multi-drug resistant organism; PO= by mouth; Q= every; Duration Treatment: 28 daysorganism; SMX/TMP= UA= UTI=ofUrinary Tract Infection; WBC= white cell count cfu= colony sulfamethoxazole/trimethoprim; forming units; DS= double strength; H=urinalysis; hour(s); MDRO= multi-drug resistant PO=blood by mouth; Q= every; SMX/TMP= UA= UTI= Urinary Tract Infection; WBC= white cell count cfu= colony sulfamethoxazole/trimethoprim; forming units; DS= double strength; H=urinalysis; hour(s); MDRO= multi-drug resistant organism; PO=blood by mouth; Q= every; †Positive urine culture: SMX/TMP= sulfamethoxazole/trimethoprim; UA= urinalysis; UTI= Urinary Tract Infection; WBC= white blood cell count 5 Women: †Positive For urine culture:2 consecutive voided urine specimens with isolation of >10 cfu/mL of the same bacterial strain 5 5 cfu/mL from 1 bacterial species For Women: Men: A single, clean-catch, voided urine specimen with isolation of >10 †Positive For urine culture:2 consecutive voided urine specimens with isolation of >10 cfu/mL of the same bacterial strain 5 cfu/mL from 1 bacterial species For Men: A single, clean-catch, voided urine specimen with isolation of >10 For Women: 2 consecutive voided urine specimens with isolation of >105 cfu/mL of the same bacterial strain ‡Nitrofurantoin: Contraindicated if CrCl< 60 mL/min AND only indicated in acute cystitis For Men: A single, clean-catch, voided urine specimen with isolation of >105 cfu/mL from 1 bacterial species ‡Nitrofurantoin: Contraindicated if CrCl< 60 mL/min AND only indicated in acute cystitis NOTE: Dosing based on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult ‡Nitrofurantoin: Contraindicated if CrCl< 60 mL/min AND only indicated in acute cystitis Patients Basedbased on Renal Function NOTE: Dosing on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Basedbased on Renal Function NOTE: Dosing on normal renal function. Refer to Table of Contents for section on Antimicrobial Dosing for Adult Patients Based on Renal Function

References: 1. Hooton TM, Bradley SF, Cardena DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 References: clinical SF, practice guidelines from the Infectious Disease of America. CID 2010;50:625-63. 1. international Hooton TM, Bradley Cardena DD, et al. Diagnosis, prevention, andSociety treatment of catheter-associated urinary tract infection in adults: 2009 References: 2. Nicolle LE, et al. Infectious Diseases Society ofthe America guidelines forSociety the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin international clinical practice guidelines from Infectious Disease of America. CID 2010;50:625-63. 1. Infect Hooton TM, Bradley SF, Cardena DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 Dis. 2005 Mar 1;40(5):643-54. 2. Nicolle LE, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin practiceclinical guidelines fromguidelines the Infectious Disease Society of America. CID 2010;50:625-63. 3. international Gupta Dis. K, et2005 al.clinical International practice for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 Infect Mar 1;40(5):643-54. 2. Nicolle LE, et al. Infectious Diseases Society America guidelines forSociety the diagnosis and treatment of asymptomatic bacteriuria inDis. adults. Clin Diseases ofof America and Microbiology and Infectious Clin Infect 2011 Mar 3. update Gupta K,byetthe al. Infectious International clinicalSociety practice guidelines forEuropean the treatment of for acute uncomplicated cystitis andDiseases. pyelonephritis in women: A 2010 Infect Dis. 2005 Mar 1;40(5):643-54. 1;52(5):e103-20. update by the Infectious Diseases Society of America and European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 3. Gupta K, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 PAGE 34 1;52(5):e103-20. update by the Infectious Diseases Society of America and European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1;52(5):e103-20.

Pneumococcal Vaccination Recommendations

E ISLA N D

Pneumococcal Vaccine Adults ≥19 Years1-4

COLLEGE OF PHARMACY

(Including updated recommendations for the use of PCV13 in Adults)

DRUG INFORMATION SERVICES 401-874-9188

LT H

D E PAR

E N T OF

Healthy Adults ≥ 65 Pneumococcal Vaccination Naive or Unknown History

Previously vaccinated with PPSV23 at age ≥65

Previously vaccinated with PPSV23 before age 65 ≥ 1 year after PPSV23

GIVE: PCV13

≥ 1 year after PPSV23

Wait ≥ 1 year*

GIVE: PPSV23†

GIVE: PCV13 if not previously given Wait ≥ 1 year* (and ≥ 5 years after PPSV23) GIVE: PPSV23†

GIVE: PCV13 if not previously given

ADULTS ≥ 19 with UNDERLYING MEDICAL CONDITIONS (see chart on back) OR who SMOKE or live in a NURSING HOME Pneumococcal Vaccination Naive or Unknown History

Previously vaccinated with one dose PPSV23

GIVE: PPSV23

At Age ≥65

GIVE: PCV13 ≥ 1 year after PPSV23 THEN: PPSV23† ≥ 1 year* after PCV13 and ≥ 5 years after PPSV23

At Age ≥65

GIVE: PCV13 ≥ 1year after PPSV23 THEN: PPSV23† ≥ 1 year* after PCV13 and ≥ 5 years after PPSV23

Vaccination is NOT indicated for healthy persons 19 - 64 years of age While PCV13 is FDA-approved for persons > 50 years, the Advisory Committee on Immune Practices does not provide guidance for use in this population.

ADULTS ≥ 19 with IMMUNE COMPROMISING CONDITIONS (see chart on back), OR ASPLENIA (including sickle cell anemia), CEREBROSPINAL FLUID LEAK, or COCHLEAR IMPLANT Pneumococcal Vaccination Naive or Unknown History GIVE: PCV13 ≥8 weeks* later

If < 65

If ≥65

GIVE: PPSV23

Previously vaccinated with one dose PPSV23 ≥ 1 year after PPSV23 GIVE: PCV13 if not previously given

PPSV23

GIVE: PCV13 if not previously given

PPSV23 GIVE: second PPSV23 §

≥ 5 years after

If ≥65

≥ 5 years after

PPSV23 GIVE: second PPSV23 §

At Age ≥65

≥ 1 year after PPSV23

≥8 weeks* later

If < 65 and If < 65 and

GIVE: PPSV23†

Previously vaccinated with two doses of PPSV23

GIVE: PPSV23†

At Age ≥65

GIVE: PPSV23† ≥ 5 years after

PPSV23

GIVE: PPSV23† ≥5 years after PPSV23

At Age ≥ 65

GIVE: PPSV23† ≥ 8 weeks* after PCV13 and ≥ 5 years after PPSV23

Minimum interval between sequential administration of PCV13 and PPSV23 is 8 weeks in immunocompromised patients. GIVE: PPSV23 For Medicare reimbursement interval must be 11 full months. Please refer to page 4. † The ACIP (Advisory Committee on Immunization Practices) recommends only 1 dose of PPSV23 at age ≥65. Revaccination is not necessary. § A second PPSV23 for patients with cerebrospinal fluid leak, or cochlear implant is not required. PPSV23=23-Valent Pneumococcal Polysaccharide Vaccine (Pneumovax®23) PCV13=13-Valent Pneumococcal Conjugate Vaccine (Prevnar 13®)

PAGE 35

Pneumococcal Vaccine

E SLA Pneumococcal Vaccination OD cina>on Informa>on

cina>on Informa>on PSV23 (Pneumovax® 23) cina>on Informa>on PSV23 (Pneumovax® 23) PSV23 (Pneumovax® 23) COLLEGE OF 1-5 LT H

D E PAR

Recommendations

PHARMACY ®23) Adults ≥19 Years na>on Informa>on Sh cina>on Informa>on S DRUG INFORMATION ®23)M E F SERVICES ®23) O N cina>on Informa>on T (Including updated recommendations for the use of PCV13 in Adults) PSV23 (Pneumovax® 23) 23 (Pneumovax® 23) 401-874-9188

PSV23 (Pneumovax® 23) 2,3 ®23) 3) PCV13 and PPSV23 Indications for Adults ≥ 19 Years* by Risk Group

®23)

cina>on Informa>on M PCV13 (Prevnar13 ) PPSV23 (Pneumovax 23) ®

PSV23 (Pneumovax® 23) Risk Group Underlying Medical Condition

®23)

Persons with normal immune function

Recommended

Cigarette smoker

✓

Chronic heart disease†

✓

Revaccinate 5 years after first dose

Pﬁ ww

Ho Pr (1

e St Chronic lung disease§ ✓ e Re cina>on Informa>on e cina>on Informa>on Diabetes mellitus ✓ St cina>on Informa>on PSV23 (Pneumovax® 23) PSV23 (Pneumovax® 23) DO PSV23 (Pneumovax® 23) Cerebrospinal fluid leak ✓ ✓ Di e ®23) e ®23) Cochlear implant£ ✓ ✓ ®23) Sp cina>on Informa>on Sh Alcoholism ✓ PSV23 (Pneumovax® 23)

Insurance

Carrie

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Department of Health State ®23) RI www.bcbsri.com/provid www.health.ri.gov/reso e Department of Health State cina>on Informa>on e Chronic renal failure ✓ ✓ ✓ HealthCare www.unitedheal althCare www.unitedhealth www.health.ri.gov/reso e Medicare www.medicaren www.health.ri.gov/reso PSV23 (Pneumovax® 23) are Part B reimburses for both the c HealthCare www.unitedhea Contraindica>ons Nephrotic syndrome ✓ ✓ ✓ Department of Health State partment of Health State Sup Contraindica>ons Contraindica>ons Department of Health State PCV13 to pa@ents who have ®23) RI www.bcbsri.com/provid Leukemia ✓ ✓ ✓ www.health.ri.gov/resour www.health.ri.gov/reso PCV13 to pa@ents who have e 13, PPSV, or one of their com www.health.ri.gov/reso PCV13 to pa@ents who have Lymphoma ✓ ✓ ✓ 13, PPSV, or one of their com HealthCare www.unitedhea Contraindica>ons an Contraindica>ons 13, PPSV, or one of their com d PCV13 simultaneously. For Contraindica>ons Hodgkin disease ✓ ✓ ✓ Insurance d PCV13 simultaneously. For Department of Health State V13 to pa@ents who have a h PCV13 to pa@ents who have a Insurance Carrie Carrie y a dose of PPSV23 at least 8 d PCV13 simultaneously. For Insurance Carrie e PCV13 to pa@ents who have Generalized malignancy ✓ ✓ ✓ y a dose of PPSV23 at least 8 13, PPSV, or one of their com PPSV, or one of their compo www.health.ri.gov/reso SV23. Medicare www.medicaren y a dose of PPSV23 at least 8 Medicare www.medicaren 13, PPSV, or one of their com SV23. Medicare www.medicaren are Part B reimburses for both the c latrogenic immunosuppression** SV23. are Part B reimburses for both the c ✓ ✓ ✓ d PCV13 simultaneously. For CV13 simultaneously. For pa@ Contraindica>ons both inac@vated vaccines. Yo are Part B reimburses for both the c (Both high and low level immunosuppression) d PCV13 simultaneously. For Insurance Carrie both inac@vated vaccines. Yo y a dose of PPSV23 at least 8 dose of PPSV23 at least 8 we f the person is a candidate fo RI www.bcbsri.com/provid both inac@vated vaccines. Yo e PCV13 to pa@ents who have RI www.bcbsri.com/provid y a dose of PPSV23 at least 8 Solid organ transplant ✓ ✓ ✓ f the person is a candidate fo 23. SV23. RI www.bcbsri.com/provid weeks and then give MCV4-‐D Medicare www.medicaren f the person is a candidate fo 13, PPSV, or one of their com SV23. weeks and then give MCV4-‐D HealthCare www.unitedhea Multiple myeloma ✓ ✓ ✓ annot give PCV13 and PPSV2 are Part B reimburses for both the c HealthCare www.unitedhea weeks and then give MCV4-‐D th inac@vated vaccines. You c both inac@vated vaccines. Yo HealthCare www.unitedhea annot give PCV13 and PPSV2 d PCV13 simultaneously. For Insurance Carrie both inac@vated vaccines. Yo Hematopoietic stem cell transplant Please refer to reference 3 for specific guidance annot give PCV13 and PPSV2 Department of Health State he person is a candidate for M f the person is a candidate fo Side Eff e Department of Health State RI www.bcbsri.com/provid y a dose of PPSV23 at least 8 Department of Health State f the person is a candidate fo Side Eff † Including congestive heart failure and cardiomyopathies, excluding hypertension. eeks and then give MCV4-‐D. I weeks and then give MCV4-‐D www.health.ri.gov/reso Medicare www.medicaren Side Eff £ If feasible, www.health.ri.gov/reso SV23. administer PCV13 and PPSV23 ≥ 2 weeks before planned cochlear implant surgery at appropriate intervals as described in the algorithm on the front page. weeks and then give MCV4-‐D ects from either PPSV23 or PC www.health.ri.gov/reso are Part B reimburses for both the c not give PCV13 and PPSV23 s annot give PCV13 and PPSV2 HealthCare www.unitedhea ∞ For PPSV23 naive patients planning splenectomy: Give PCV13; wait at least 8 weeks then give PPSV23. Do not give PPSV23 within 2 weeks of planned splenectomy. ects from either PPSV23 or PC Contraindica>ons annot give PCV13 and PPSV2 § Including chronic obstructive pulmonary disease, emphysema, and asthma. Insurance Carrie ects from either PPSV23 or PC Contraindica>ons both inac@vated vaccines. Yo ¶ Includes B- (humoral) or T-lymphocyte deficiency, complement deficiencies (particularly C1, C2, C3, and C4 deficiencies), and phagocytic disorders (excluding chronic granulomatous disease). Contraindica>ons Side Effe Side Eff Department of Health State RI www.bcbsri.com/provid ** Those requiring treatment with immunosuppressive drugs, including long-term systemic corticosteroids and radiation. f the person is a candidate fo PCV13 to pa@ents who have Side Eff ma>on Services 401-‐874-‐918 Medicare www.medicaren PCV13 to pa@ents who have REFERENCES: www.health.ri.gov/reso PCV13 to pa@ents who have ma>on Services 401-‐874-‐918 weeks and then give MCV4-‐D 13, PPSV, or one of their com ects from either PPSV23 or PC s from either PPSV23 or PCV1 1. Immunization Services Division, National Center for Immunization and Respiratory Diseases, CDC. Advisory Committee on Immunization Practices (ACIP) are Part B reimburses for both the c HealthCare www.unitedhea 13, PPSV, or one of their com ma>on Services 401-‐874-‐918 c@on Coali@on (www.immunize.org) in coll Recommended Immunization Schedules for Persons Aged 0 Through 18 years and Adults Aged 19 Years and Older - United States, 2013. 13, PPSV, or one of their com ects from either PPSV23 or PC annot give PCV13 and PPSV2 September 4, 2013. MMWR 2012; 61(40):8 c@on Coali@on (www.immunize.org) in coll Carrie MMWR Morb Mortal Wkly Rep.Contraindica>ons 2013;62(Suppl):9-19. Insurance d PCV13 simultaneously. For c@on Coali@on (www.immunize.org) in coll September 4, 2013. MMWR 2012; 61(40):8 2. CDC. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: Department of Health State RI www.bcbsri.com/provid d PCV13 simultaneously. For September 4, 2013. MMWR 2012; 61(40):8 d PCV13 simultaneously. For recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2012;61(40):816-819. y a dose of PPSV23 at least 8 Side Eff a>on Services 401-‐874-‐9188 ma>on Services 401-‐874-‐918 Medicare www.medicaren PCV13 to pa@ents who have y a dose of PPSV23 at least 8 www.health.ri.gov/reso 3. CDC. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among adults aged ≥ 19 years: Recommendations of the Advisory ma>on Services 401-‐874-‐918 y a dose of PPSV23 at least 8 are Part B reimburses for both the c SV23. Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2014;63(37):822-825. HealthCare www.unitedhea 13, PPSV, or one of their com n Coali@on (www.immunize.org) in collabor c@on Coali@on (www.immunize.org) in coll SV23. 4. Kobayashi M, Bennett NM, Gierke R, et al. Intervals between PCV13 and PPSV23 vaccines: Recommendations of the Advisory Committee in Immunization Practice (ACIP) ects from either PPSV23 or PC SV23. tember 4, 2013. MMWR 2012; 61(40):816-‐8 September 4, 2013. MMWR 2012; 61(40):8 c@on Coali@on (www.immunize.org) in coll MMWR Morb Mortal Wkly Rep.Contraindica>ons 2015; 64(34): 944-947. both inac@vated vaccines. Yo September 4, 2013. MMWR 2012; 61(40):8 Department of Health State RI www.bcbsri.com/provid d PCV13 simultaneously. For 5. Rubin LG, Levin MJ, Davies EG, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:e44-e100. doi: 10.1093/cid/cit684. both inac@vated vaccines. Yo both inac@vated vaccines. Yo f the person is a candidate fo PCV13 to pa@ents who have y a dose of PPSV23 at least 8 www.health.ri.gov/reso f the person is a candidate fo ma>on Services 401-‐874-‐918 f the person is a candidate fo HealthCare www.unitedhea PAGE 36 weeks and then give MCV4-‐D 13, PPSV, or one of their com SV23. weeks and then give MCV4-‐D weeks and then give MCV4-‐D Contraindica>ons c@on Coali@on (www.immunize.org) in coll annot give PCV13 and PPSV2 annot give PCV13 and PPSV2 Department of Health State September 4, 2013. MMWR 2012; 61(40):8 d PCV13 simultaneously. For both inac@vated vaccines. Yo annot give PCV13 and PPSV2 PCV13 to pa@ents who have y a dose of PPSV23 at least 8 www.health.ri.gov/reso Side Eff f the person is a candidate fo Side Eff 13, PPSV, or one of their com Side Eff

Pneumococcal Vaccine Pneumococcal Vaccination Information Sheet PCV13 (Prevnar 13®) and PPSV23 (Pneumovax® 23)

COLLEGE OF PHARMACY

Facts About Pneumococcal Disease: • Streptococcus pneumoniae bacteria (i.e., pneumococci) are usually found in the upper respiratory tract of most people. • Pneumococcal disease most commonly presents as a serious infection in the lungs (pneumonia), blood (bacteremia), or brain (meningitis). The annual U.S. case estimate for invasive pneumococcal disease (bacteremia and/or meningitis) is 40,000 and 4,250 deaths. • Pneumococcal disease most often occurs in older people as well as in people with a predisposing condition (e.g., immunosuppression, pulmonary disease, heart disease, diabetes). The disease rates for adults in these groups can be more than 20 times those for adults without high-risk medical conditions. • PPSV23 is 60–70% effective in preventing serious pneumococcal disease; it does not provide substantial protection against all types of pneumonia (viral and bacterial). It is not a “pneumonia” vaccine.

Frequently Asked Questions: Question: Can I get the influenza and pneumococcal vaccines at the same time? Yes. These vaccines can be given at the same time. If giving two IM vaccinations, separate by one inch in the body muscle to reduce likelihood of local reactions overlapping. Question: If patients who are in a recommended risk group for PPSV23 or PCV13 aren’t sure if they have previously received these vaccines, should healthcare providers vaccinate them? Yes. If patients do not have a documented vaccination history for these two vaccines and their records are not readily obtainable, you should administer the recommended doses. Extra doses will not cause harm to the patient. Question: Is an egg allergy a contraindication for PCV13 or PPSV23? No. Both vaccinations are safe for persons with egg allergies. Question: If my state has a registry, do I still need to give patients vaccine record cards? Yes. Patient-held cards are an extremely important part of a person’s medical history. The person may move to an area without a registry, and a personal record may be the only vaccination record available. In addition, even within a state, all healthcare providers may not participate in the registry, and the personal record card would be needed. Question: My patient has had laboratory-confirmed pneumococcal pneumonia. Does he/she still need to be vaccinated with PPSV23? Yes. There are more than 90 known serotypes of pneumococcus (23 serotypes are in the current vaccine). Infection with one serotype does not necessarily produce immunity to other serotypes. As a result, if the person is a candidate for vaccination, he/she should receive it even after one or more episodes of invasive pneumococcal disease. Question: Why is pneumococcal vaccination recommended for smokers and asthmatics? In 2008, the Advisory Committee on Immunization Practices (ACIP) reviewed new information that suggests that asthma is an independent risk factor for pneumococcal disease among adults. ACIP also reviewed new information that demonstrates an increased risk of pneumococcal disease among smokers. Consequently, ACIP recommends to include both asthma and cigarette smoking as risk factors for pneumococcal disease among adults age 19 through 64 years and as indications for PPSV23. Acquired from www.immunize.org on September 4, 2013. We thank the Immunization Action Coalition. MMWR Morb Mortal Wkly Rep 2012; 61(40):816-819.

PAGE 37

Pneumococcal Vaccine Pneumococcal Vaccination Information Sheet PCV13 (Prevnar 13®) and PPSV23 (Pneumovax® 23)

COLLEGE OF PHARMACY

PPSV23 (Pneumovax®23)

PCV13 (Prevnar13®)

Manufacturer:

Merck www.merckvaccines.com/Products/Pneumovax/Pages/home

How Supplied:

Pfizer http://www.pfizerpro.com/hcp/prevnar13

How Supplied:

0.5mL Single Dose Vial Multi-Dose (5 dose Vial)

Prefilled Syringe (10 per Package)

Storage and Handling:

Refrigerate on Arrival Store at 2◦C to 8◦C DO NOT FREEZE Discard after the expiration date

Special instructions:

None

Shake well to obtain a homogeneous white suspension

Route of Administration:

0.5mL IM or SQ

0.5mL IM ONLY

Insurance Carrier Information: Medicare www.medicarenhic.com 1-866-801-5304* BCBS of RI www.bcbsri.com/providers 401-274-4848 1-800-230-9050 UnitedHealthCare www.unitedhealthcareonline.com 1-877-842-3210 RI Department of Health State Supplied Vaccination Program www.health.ri.gov/resources/immunization/

Contraindications and Precautions: • Do not give PPSV23 or PCV13 to patients who have a history of a serious reaction (e.g., anaphylaxis) after a previous dose of PCV13, PPSV23, or one of their components. • Do not give PPSV23 and PCV13 simultaneously. For vaccine naive patients, give PCV13 first, followed by a dose of PPSV23 ≥ 1 year† (unless patient in a population specified by ACIP to require shorter interval, see page 1). For patients who have already received PPSV23, give PCV13 12 months after the most recent dose of PPSV23. • Vaccine Co-administration: (1) all vaccines used for routine vaccination in the United States can be given on the same day; (2) an inactivated vaccine can be administered either on the same day as or at any time before or after another inactivated or a live vaccine; and (3) any 2 LIVE vaccines that are not given on the same day must be spaced at least 4 weeks apart. Zoster vaccine is a live, attenuated vaccine; injectable influenza vaccine and pneumococcal polysaccharide vaccine are inactivated vaccines. So these 3 vaccines can be given on the same day or at any time before or after each other. They should be given as separate injections, not combined in the same syringe.

Side Effects: • Most common side effects from either PPSV23 or PCV13 are soreness and redness at the injection site, lasting 1-2 days. Drug Information Services 401-874-9188

Monday-Friday 8:30 am - 4:00 pm EST

initial pneumococcal vaccine may be administered to all Medicare beneficiaries who have never received a pneumococcal vaccine under Medicare Part B. A different, second * An pneumococcal vaccine may be administered 1 year after the first vaccine was administered (i.e., 11 full months have passed following the month in which the last pneumococcal vaccine was administered). Please note that the “interval” between the two different pneumococcal vaccines must be at least 11 full months or greater for Medicare reimbursement, not the shorter “interval” recommended for specific populations identified by ACIP. Acquired from www.immunize.org on September 4, 2013. We thank the Immunization Action Coalition.

† Kobayashi M, Bennett NM, Gierke R, et al. Intervals between PCV13 and PPSV23 vaccines: Recommendations of the Advisory Committee in Immunization Practice (ACIP) MMWR Morb Mortal Wkly Rep. 2015; 64(34): 944-947.

PAGE 38

100

273

28*

19*

Enterobacter cloacae

Escherichia coli

Klebsiella oxytoca

Klebsiella pneumoniae

Morganella morganii

Proteus mirabilis

Providencia spp.

Pseudomonas aeruginosa

Serratia marcescens

Ampicillin

100

*If < 30 isolates use caution extrapolating results; data may be inconclusive for therapeutic efficacy and selection of empiric treatment.

Amoxicillin /Clavulanic acid

Ampicillin /Sulbactam

Aztreonam

Cefazolin

Cefepime

100

11*

Enterobacter aerogenes

Cefotaxime

100

13*

Citrobacter freundii

Ceftazidime 50

Ceftriaxone

Cefuroxime

Ciprofloxacin

Ertapenem

Gentamicin

Meropenem

Nitrofurantoin

---

100

Piperacillin/ tazobactam

Tetracycline

100

10*

100

Sulfamethoxazole /Trimethoprim

Total # Isolates

Acinetobacter spp.

100

Tobramycin

Stenotrophomonas maltophilia Haemophilus influenzae

Amikacin

Gram Negative Organisms: Inpatient/Outpatient

2018 Antibiogram (Percent Susceptible)

2018 Antibiogram

PAGE 39

Total # Isolates

137

12*

Enterococcus faecalis

Enterococcus faecium

175

13*

Staphylococcus (coag. neg.)

Streptococcus pneumoniae

100

*If < 30 isolates use caution extrapolating results; data may be inconclusive for therapeutic efficacy and selection of empiric treatment.

Amoxicillin /Clavulanate

100

Ampicillin /Sulbactam

Cefazolin

176

Ciprofloxacin

Clindamycin

Daptomycin

Erythromycin

Gentamicin

Moxifloxacin

Nitrofurantoin

Oxacillin

Penicillin G

Tetracycline

Streptomycin

100

Sulfamethoxazole /Trimethoprim

100

Vancomycin

Staphylococcus aureus (MSSA) Staphylococcus aureus, Methicillin-resistant (MRSA)

Ampicillin

Gram Positive Organisms: Inpatient/Outpatient

2018 Antibiogram (Percent Susceptible)

2018 Antibiogram

PAGE 40

Guidelines for Restricted Antimicrobials I.

• • • • • • • • • • • • • •

• • II.

The use of the following formulary antimicrobial agents are restricted Antibiotics Ceftaroline (Teflaro®) Ceftazidime/avibactam (Avycaz®) Ceftolozane/tazobactam (Zerbaxa®) Colistin (Polymyxin E) Dalbavancin (Dalvance®) Daptomycin (Cubicin®) Delafloxacin (Baxdela®) Ertapenem (Invanz®) Fidaxomicin (Dificid®) Fosfomycin (Monurol®) Linezolid (Zyvox®) Meropenem and Vaborbactam (Vabomere®) Oritavancin (Orbactiv®) Polymyxins Polymyxin B Colistin (Polymyxin E) Tedizolid (Sivextro®) Tigecycline (Tygacil®)

• • • • •

Antifungals Amphotericin B lipid complex (AmBisome®) Caspofungin (Cancidas ®) Isavuconazonium sulfate (Cresemba®) Voriconazole (V-Fend®) Monoclonal Antibody Bezlotoxumab (Zinplav®)

To ensure the rational use of formulary, restricted, or non-formulary antimicrobial agents, the following policies and procedures are to be used:

When a prescriber wishes to prescribe a restricted or non-formulary antimicrobial agent, he/she shall indicate the “approved” reason (see following pages) in the comments section of the order form. If the use is outside of an approved indication, the physician MUST obtain approval of use. This approval must be obtained from the Infectious Diseases consult team, by directly contacting the on-call Infectious Diseases physician/fellow or by calling the Department of Medicine who will contact the on-call Infectious Diseases physician/fellow.

When pharmacy receives an order for a restricted antimicrobial agent, the pharmacist will verify the “approved” reason for use and if applicable, fill the order. If the pharmacy receives an order for a restricted or non-formulary antimicrobial agent and the ordering box does not indicate an approved reason for use, the pharmacist will immediately contact the prescriber to obtain “criteria for use of a restricted agent.”

If the prescriber cannot be reached, the pharmacist will dispense a maximum 24 hour supply of the drug. The pharmacist MUST notify the prescriber that further drug will be dispensed only when the completed order form or ID approval is received. It is up to the prescriber to obtain authorization from the Infectious Diseases fellow or Infectious Diseases consult team.

Ceftaroline (Teflaro®) Ceftaroline (Teflaro®) IV Only

Use requires formal ID Consult

Activity: Coverage against Staphylococcus aureus (MSSA and MRSA), Staphylococcus epidermidis (including MSRE), Streptococcus pneumoniae, most gram-negatives, and some gram-positive anaerobic bacteria NOT ACTIVE against Pseudomonas spp., Acinetobacter spp., resistant gram-negative bacteria (ESBL producers, carbapenemase producers, and AmpCs) or Enterococcus spp. Criteria for Use: • Acute bacterial skin and skin structure infection (ABSSSI) caused by MRSA +/bacteremia or community-acquired bacterial pneumonia (CABP) • Unable to use vancomycin (VAN; due to intolerance, MIC ≥ 2 mg/mL, or infection unresponsive to VAN despite therapeutic concentrations) • Unable to use other agents (refer to empiric therapy for ABSSSI/CABP) Unacceptable Uses: • Treatment of P. aeruginosa, Enterococcus spp., or Acinetobacter spp. Infections (limited to no activity) • Treatment of ESBL producing organisms, such as E. coli or Klebsiella spp. (inactivated by AmpC and ESBL beta-lactamases) • Known serious hypersensitivity to ceftaroline or other members of the cephalosporin class. Cross-reactivity may occur in patients with a history of other beta-lactam allergies Dosing in Adults: • Standard dose: 600 mg IV Q12H For MSSA/MRSA bacteremia consider: 600 mg IV Q8H • Renal dose adjustment: CrCl 30-50 mL/min: 400 mg IV Q12H CrCl 15-30 mL/min: 300 mg IV Q12H CrCl <15 mL/min: 200 mg IV Q12H Hemodialysis: 200 mg IV Q12H • All infusions should be over 1 hour • No hepatic dose adjustment Monitoring: • Monitor CBC for drug-induced hemolytic anemia (none observed in studies, but seroconversion from negative to positive Direct Coombs’ Test is observed in 10.8% on ceftaroline vs 4.4% on comparator) ABSSSI= Acute bacterial skin and skin structure infection; CABP= community-acquired bacterial pneumonia; CBC= Complete blood count; CrCl= Creatinine clearance; ESBL= Extended spectrum beta-lactamase; H= hour(s); ID= infectious diseases; IV= Intravenous; MIC= Minimum inhibitory concentration; MRSA= Methicillin-resistant Staphylococcus aureus; MSSA= Methicillin-susceptible Staphylococcus aureus; Q= every; spp= Species; VAN= vancomycin

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Ceftazidime/avibactam (Avycaz®) Ceftazidime/avibactam (Avycaz®) IV Only

Use requires formal ID Consult

Activity: Coverage against many resistant gram-negatives such as Enterobacteriaceae and Pseudomonas aeruginosa, including some ESBL producers (e.g. CTX-M), carbapenemases (e.g. KPC, some OXA ), and AmpCs NOT ACTIVE against MBLs or gram-negatives that overexpress efflux pumps or have porin mutations, most anaerobic bacteria, most Staphylococcus spp., and Enterococcus spp. Criteria for Use: • Treatment of cIAI (in combination with metronidazole) or cUTI, including pyelonephritis, caused by MDR gram-negative organisms Unacceptable Uses: • Empiric use without confirmed susceptibility • Treatment of cIAI and cUTI with other available treatment options • Known serious hypersensitivity to the components of ceftazidime/avibactam, avibactam-containing products, or other members of the cephalosporin class. Cross-reactivity may occur in patients with a history of penicillin allergy Dosing in Adults: • Standard dose: 2.5gm IV Q8H For cIAI must use in combination with metronidazole • Renal dose adjustment: CrCl 31 - 50 mL/min: 1.25gm IV Q8H CrCl 16-30 mL/min: 0.94gm IVQ12H CrCl 6-15 mL/min: 0.94gm IV Q24H CrCl <5 mL/min: 0.94gm IV Q48H Administer after hemodialysis • No hepatic dose adjustment anticipated Monitoring: • Scr/BUN at baseline and daily; adjust dose accordingly. CBC with differential. Monitor for signs of anaphylaxis with first dose Considerations for Use: • Decreased efficacy in patients with = CrCl 30-50 mL/min in clinical trials • CNS reactions have been reported in patients treated with ceftazidime, particularly in the setting of renal impairment BUN= blood urea nitrogen; CBC= Complete blood count; cIAI= Complicated intraabdominal infections; CNS= Central nervous system; CrCl= Creatinine clearance; cUTI= complicated urinary tract infections; ESBL= extended-spectrum beta-lactamases; H= hour(s); ID= infectious diseases; IV= Intravenous; KPC= Klebsiella pneumoniae carbapenemases; MBL= metallo-betalactamases; MDR= multi-drug resistant; Q= every; Scr= Serum creatinine

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Ceftolozane/tazobactam (Zerbaxa®) IV Only

Use requires formal ID Consult

Activity: Coverage against many MDR gram-negatives such as Enterobacteriaceae and Pseudomonas aeruginosa. Potent in vitro activity against most P. aeruginosa isolates, including some MDR and carbapenem-resistant strains. Inhibits many Enterobacteriaceae, including some ESBL producers (e.g. CTX-M) and some AmpCs NOT ACTIVE against serine carbapenemases (e.g. KPCs or MBLs), most anaerobic bacteria, Staphylococcus spp., and Enterococcus spp. Criteria for Use: • Complicated intra-abdominal infections (cIAI, in combination with metronidazole); complicated urinary tract infections (cUTI), including pyelonephritis; or hospital-acquired bacterial pneumonia and ventilatorassociated pneumonia (HABP/ VABP); caused by MDR gram-negative organisms Unacceptable Uses: • Empiric use without confirmed susceptibility • Treatment of cIAI, cUTI, or HABP/ VABP with other available treatment options • Known serious hypersensitivity to ceftolozane/tazobactam, piperacillin/tazobactam, or other members of the beta-lactam class Dosing in Adults: • cIAI or cUTI: 1500 mg IV Q8H For cIAI must use in combination with metronidazole 500mg IV q8H • HABP/VABP: 3000 mg IV Q8H • Renal dose adjustment if usual dose is 1500 mg IV Q8H: CrCl 30-50 mL/min: 750 mg IV Q8H CrCl 15-29 mL/min: 375 mg IV Q8 Hemodialysis: 750mg IV ONCE (load), then 150mg IV Q8H after dialysis • Renal dose adjustment if usual dose is 3000 mg IV Q8H: CrCl 30-50 mL/min: 1500 mg IV Q8H CrCl 15-29 mL/min: 750 mg IV Q8H Hemodialysis: 2250 mg IV ONCE (load), then 450mg IV Q8H after dialysis • No hepatic dose adjustment anticipated Monitoring: • Scr/BUN, CBC with differential at baseline and daily Considerations for Use: • Package insert states decreased efficacy seen in patients with a baseline CrCl <50mL/min or patients >65 years of age, in the cIAI trial • May have a role in the treatment of other infections caused by multidrug resistant gram-negatives, however alternate dosing may be recommended depending on site of infection. ID team must be consulted for all potential on and off label use BUN= blood urea nitrogen; CBC= Complete blood count; cIAI= Complicated intraabdominal infections; CrCl= Creatinine clearance; cUTI= complicated urinary tract infections; ESBL= extended-spectrum beta-lactamases; ID= infectious disease; IV= Intravenous; KPC= Klebsiella pneumoniae carbapenemases; MBL= metallo-beta-lactamases; MDR= multi-drug resistant; Q= every; H= hour(s); Scr= Serum creatinine

Dalbavancin (Dalvance®) Dalbavancin (Dalvance®) IV Only

Use requires formal ID Consult

Activity: Coverage against Staphylococcus aureus (including MSSA and MRSA), Streptococcus pyogenes, Streptococcus agalactiae (Group B Strep.) and Streptococcus anginosus group (including S. anginosus, S. intermedius, S. constellatus) No clinical data, but activity in vitro vs. Enterococcus faecalis (vancomycin-susceptible strains only), Enterococcus faecium (vancomycin-susceptible strains only), vancomycin-intermediate S. aureus (not vancomycin-resistant strains) Criteria for Use: • Treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive isolates • Unable to use vancomycin (due to intolerance, MIC >2mg/L, or infection unresponsive to vancomycin despite therapeutic concentrations) • Unable to use other agents (refer to empiric therapy for ABSSSI) Unacceptable Uses: • Infections due to vancomycin-resistant enterococci • Contraindicated in patients with known hypersensitivity to dalbavancin. Due to the possibility of cross-reactivity to glycopeptide, avoid in patients with previous glycopeptide hypersensitivity due to long half-life Dosing in Adults: • Standard dose: Administration should be over 30 minutes 1 Dose Regimen: 1500mg IV once 2 Dose Regimen: 1000mg IV once, then 500mg IV on day 8 • Renal dose adjustment: 1 Dose Regimen CrCl <30 mL/min 1125 mg IV 2 Dose Regimen CrCl <30 mL/min: 750mg IV once, then 325mg IV day 8 If receiving regularly scheduled hemodialysis: No dosage adjustment • No hepatic dose adjustment anticipated Monitoring: • Baseline BUN/Scr, AST/ALT/bili, CBC w/ diff, infusion-related reactions Considerations for Use: • In clinical trials, 6 (0.9%) patients in the dalbavancin arm had ALT elevations greater than 5x ULN including 3 with ALT >10x ULN. No subjects in the comparator arm had this degree of ALT elevations ABSSSI= acute bacterial skin and skin structure infections; ALT= Alanine aminotransferase; AST= Aspartate aminotransferase; bili= Bilirubin; BUN= Blood urea nitrogen; CBC= Complete Blood Count; CrCl= Creatinine clearance; ID= infectious diseases; IV= Intravenous; MIC= Minimum inhibitory concentration; MRSA= Methicillin-resistant Staphylococcus aureus; MSSA= Methicillin-susceptible Staphylococcus aureus; SCr= Serum creatinine; ULN= Upper Limit of Normal

PAGE 45

Daptomycin (Cubicin®) Daptomycin (Cubicin®) IV Only

Use requires formal ID Consult

Activity: Coverage against most gram-positive bacteria (including MRSA and VRE) NOT ACTIVE against gram-negative bacteria Criteria for Use: • MRSA bacteremia and/or right-sided endocarditis and unable to use vancomycin (due to intolerance, MIC ≥ 2 mg/L, or infection unresponsive to vancomycin despite therapeutic concentrations) • MRSA skin and skin structure infections in patients with true, serious allergic reaction to vancomycin or linezolid • Patients receiving vancomycin for > 72 h for resistant staphylococcal skin and skin structure infection without clinical improvement • VRE confirmed bacteremia (see dosing below, use high doses) Formal ID consult for use in osteomyelitis or complicated skin and soft tissue infection and all indications that are not listed above Unacceptable Uses: • Empiric therapy • Pneumonia (lung surfactant inactivates daptomycin) or any lower respiratory tract infection Dosing in Adults: • Standard dose: 6-10 mg/kg IV Q24H of actual body weight (ABW) May be dosed 8-10 mg/kg for Enterococcus (safety data for healthy volunteers up to 12 mg/kg/day) • Renal dose adjustment: CrCl < 30 mL/min: 8 mg/kg IV Q48H Hemodialysis: 8 mg/kg IV Q48H • No hepatic dose adjustment Monitoring: • Obtain CPK at baseline and weekly. Monitor for muscle pain or weakness, and for signs/symptoms of eosinophilic pneumonia Considerations for Use: • Consider discontinuation of concurrent statin therapy while on daptomycin due to additive muscle toxicity ABW= Actual Body Weight; CPK= Creatine phosphokinase; CrCl= Creatinine clearance; H= hour(s); ID= Infectious Disease; IV= Intravenous; MIC= Minimum inhibitory concentration; MRSA= Methicillin-resistant Staphylococcus aureus; Q= every; VRE= Vancomycin-resistant enterococci

PAGE 46

Delafloxacin (Baxdela ) Delafloxacin (Baxdela ) TM

PO and IV Only

Use requires formal ID Consult

Fluoroquinolone antibiotic with FDA-approval for acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria in adults. Activity: Coverage against gram-positive organisms (eg. Staphylococcus aureus (MRSA and MSSA), Streptococcus spp., and Enterococcus faecalis), gram-negative organisms (eg. Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Also covers some anaerobes and atypical respiratory tract pathogens. Criteria for use: • Treatment of adult patients with ABSSSI caused by susceptible organisms when unable to use any other agents (refer to empiric therapy for ABSSSI) Unacceptable Uses: • Patients with ESRD (eg. hemodialysis) or eGFR < 15 mL/min/1.73m2, PO or IV delafloxacin use not recommended due to insufficient information • Contraindicated in patients with known hypersensitivity to delafloxacin or any agents in the fluoroquinolone class of antibiotics Dosing in Adults: • Standard: 300 mg IV over 60 min Q12H, or 450 mg PO Q12H • Renal impairment dose adjustments: (based on eGFR NOT CrCl) - eGFR 15-29 mL/min/1.73m2 - 200 mg Q12H IV (NOT for PO) - eGFR < 15 mL/min/1.73m2 - NOT RECOMMENDED for both IV and PO • Treatment duration ranges from 5 to 14 days • Oral formulation may be given with or without food, but must be spaced with any multivalent cations (eg. Ca2+, Mg2+) 2 hours before and 6 hours after dose Monitoring: • SCr/BUN (particularly in patients with underlying renal dysfunction) Considerations for Use: • Unlike other fluoroquinolones, delafloxacin does not appear to have a risk of photosensitivity or QTc prolongation. • Assess for potential drug-drug interactions • Intravenous delafloxacin is formulated with sulfobutylether-βcyclodextrin vehicle, which may accumulate in patients with severe renal dysfunction (see above dose adjustment recommendations). • Black box warning: Fluoroquinolones have been associated with tendinitis and tendon rupture, peripheral neuropathy, and central nervous system (CNS) effects. Avoid use in patients with history/current myasthenia gravis, tendinitis or tendon rupture, and peripheral neuropathy. ABSSSI= acute bacterial skin and skin structure infections; BUN= blood urea nitrogen; Ca2+= calcium; CrCl= Creatinine Clearance; ESRD= end-stage renal disease; eGFR= estimated glomerular filtration rate; FDA= Food and Drug Administration; H= hour(s); ID= infectious diseases; IV= Intravenous; m= meters; Mg2+= magnesium; MRSA=methicillin-resistant Staphylococcus aureus; MSSA= methicillin-susceptible Staphylococcus aureus; PO= Oral; Q= every; SCr= serum creatinine References: Baxdela (Delafloxacin) [package insert]. Melinta Therapeutics, Inc; Lincolnshire (Il): June 2017.

PAGE 47

Ertapenem (Invanz®) Ertapenem (Invanz®) IV and IM Only

Use requires formal ID Consult

Activity: Coverage against many gram-negatives (including those that produce ESBL), gram-positives, and anaerobes NOT ACTIVE against Pseudomonas spp., Acinetobacter spp., MRSA, or Enterococcus spp. Criteria for Use: • Outpatient treatment of community acquired infections; outpatient settings Unacceptable Uses: • Caution use of ertapenem in organisms producing AmpC beta-lactamase without testing the organisms specifically against ertapenem susceptibility • Contraindicated in patients with documented hypersensitivity to beta-lactams • Treatment of P. aeruginosa, Acinetobacter spp., MRSA, or Enterococcus spp. Infections Dosing in Adults: • Standard dose: 1 gm IV or IM Q24H • Renal dose adjustment: CrCl < 30 mL/min: 500 mg IV or IM Q24H Hemodialysis: 500 mg IV or IM Q24H; supplemental dose of 150 mg after dialysis if last 500 mg dose given within 6 hours prior to dialysis, no supplemental dose necessary if last 500 mg dose given at least 6 hours prior to dialysis • No hepatic dose adjustment Monitoring: • Fever, CBC, hepatic function, pulmonary function (in pneumonia) CBC= Complete blood count; CrCl= Creatinine clearance; ESBL= Extended spectrum beta-lactamase; H= hour(s); ID= Infectious Disease; IM= Intramuscular; IV= Intravenous; MRSA= Methicillin-resistant Staphylococcus aureus; Q= every; Spp= Species

PAGE 48

Fidaxomicin (Dificid®) Fidaxomicin (Dificid®) PO Only Patients with multiple Clostridium difficile infection (CDI) recurrences (i.e. severe or mild-moderate CDI with greater than 2 and 3 recurrences, respectively) or severe, complicated CDI should obtain ID and/or GI consult for optimal therapy Criteria for Use: • Patients with a non-severe or severe initial episode of CDI OR • Patients with a 1st recurrence of CDI who were previously treated with vancomycin for the initial episode OR • Patients with ≥2 recurrences Unacceptable Uses: • Treatment of systemic infections • Treatment of severe, complicated CDI (i.e., life-threatening or fulminant CDI or toxic megacolon) • Use in combination with PO vancomycin or PO metronidazole Dosing in Adults: • Standard dose: 200 mg PO Q12H for 10 days • No renal or hepatic dose adjustment • May be given with or without food; systemic absorption is minimal Considerations for Use: • The Society for Healthcare Epidemiology in America (SHEA) and Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines for CDI recommend to discontinue therapy with the inciting antimicrobial as soon as possible, as this may influence the risk of CDI recurrence • Evidence to support using fidaxomicin for multiply recurrent CDI is limited. Fidaxomicin was only studied in patients with an initial episode or 1st recurrence (defined as within 3 months of initial episode). Recurrence rates in both phase III studies were significantly lower in patients treated with fidaxomicin. However, in a subgroup analysis, recurrence rates were NOT significantly lower in fidamoxicin-treated patients who had the hyper-virulent BI/NAP1/O27 strain • Fidaxomicin is a macrolide antibiotic: use with caution in patients with a reported macrolide allergy CDI= Clostridium difficile infection; FDA= Food and Drug Administration; GI= gastrointestinal; H= hour(s); ID= infectious diseases; IDSA= Infectious Diseases Society of America; PO= Oral; Q= every; SHEA= Society for Healthcare Epidemiology in America

PAGE 49

Fosfomycin (Monurol®) Fosfomycin (Monurol®) PO Only

Use requires formal ID Consult

Activity: Coverage against many gram-negatives (including ESBL-producing and carbapenem-resistant Enterobacteriaceae [such as E. coli, Klebsiella spp.]) and grampositives (including MRSA and VRE) NOT ACTIVE against Acinetobacter spp. In the United States only the oral formulation is available. Criteria for Use: • Management of uncomplicated UTI in patients with multiple antibiotic allergies and/or when no other oral therapy options are available • Uncomplicated UTI due to VRE • Salvage therapy for UTI due to multi-drug resistant organisms (e.g. ESBL, VRE, +/- Pseudomonas; confirm fosfomycin susceptibility prior to initiation of therapy) Unacceptable Uses: • Management of any infections outside of the urinary tract. Oral fosfomycin does not achieve adequate concentrations at other sites • Treatment of asymptomatic bacteriuria Dosing in Adults: • Standard dose: Uncomplicated UTI: 3 gm (1 sachet) PO once Complicated UTI: 3 gm (1 sachet) PO every 2 to 3 days (up to 21 days of treatment) Powder should be mixed with 90-120 mL of cool water, stirred to dissolve and administered immediately. May be administered with or without food • No renal dose adjustment • No hepatic dose adjustment Monitoring: • Signs and symptoms of urinary tract infection CrCl= Creatinine clearance; ESBL= Extended spectrum beta-lactamase; ID= Infectious Disease; MRSA= Methicillin-resistant Staphylococcus aureus; PO= Oral; Spp= Species; UTI= Urinary Tract Infection; VRE= Vancomycin-resistant enterococci

PAGE 50

Linezolid (Zyvox®) Linezolid (Zyvox®) IV and PO Only

Use requires formal ID Consult

Activity: Coverage against Staphylococcus aureus (MSSA and MRSA), Streptococcus pneumoniae, VRE Criteria for Use: • Vancomycin (VAN) MIC ≥ 2 mg/L in MRSA pneumonia • Patient with allergy to beta-lactams/vancomycin and organism resistant to other antimicrobials • Significant VRE infections (i.e. isolated from a sterile site: blood, abscess) • Infections due to MRSA in patient with well documented intolerance to VAN (NOTE: Red man syndrome is not a serious intolerance to VAN) Formal ID consult for use in osteomyelitis or complicated skin and soft tissue infection and all indications that are not listed above Unacceptable Uses: • Empiric use when VRE has not been cultured or documented • Uncomplicated urinary tract infection • Positive respiratory culture for VRE • VRE colonization Dosing in Adults: • Standard dose: 600 mg PO or IV Q12H In patients tolerating PO medications, should be given orally Oral formulation is completely absorbed and has 100% availability • No renal or hepatic dose adjustment Monitoring: • CBC at baseline and weekly (MONITOR platelets at baseline and weekly) Considerations for Use: • Caution in patients with thrombocytopenia. 3 percent of patients were noted to have a platelet decrease <75% of baseline or lower limit of normal in controlled trials (therapy <28 days, most < 21 days). Thrombocytopenia is reversible upon discontinuation and is correlated with duration • Linezolid is a weak MAOI. Use in caution with decongestants (i.e. pseudoephedrine) and serotonergic agents (i.e. SSRIs [fluoxetine, escitalopram, sertraline, paroxetine, citalopram]) Warn patients to avoid large quantities of tyramine containing foods CBC= Complete blood count; H= hour(s); ID= infectious disease; IV= Intravenous; MAOI= Monoamine oxidase inhibitors; MIC= Minimum inhibitory concentration; MRSA= Methicillin-resistant Staphylococcus aureus; MSSA= Methicillin-susceptible Staphylococcus aureus; PO= Oral; Q= every; SSRI= serotonin-specific reuptake inhibitors; VAN= Vancomycin; VRE= Vancomycinresistant enterococci

PAGE 51

Meropenem Meropenemand andVaborbactam Vaborbactam(Vabomere (Vabomere) ) TM

IV Only

Use requires formal ID Consult

Carbapenem and beta-lactamase inhibitor antibiotic combination with FDA-approval for patients ≥18 years old with complicated urinary tract infections including pyelonephritis caused by proven susceptible bacteria Activity: Coverage against many resistant gram negatives such as Enterobacteriaceae and Pseudomonas aeruginosa, including some CREs, KPCs and some ESBLs (e.g. CTX-M)1,2 NOT ACTIVE against certain carbapenemases including MBLs (e.g. NDM, VIM) and/or oxacillinases (e.g. OXA-48, OXA-163) Criteria for use: • Treatment of complicated urinary tract infections including pyelonephritis caused by MDR gram negative organisms, when unable to use any other agents Unacceptable Uses: • Empiric use without confirmed susceptibility • Treatment of complicated urinary tract infections when other agents are available • Known serious hypersensitivity to meropenem, vaborbactam or to other members of the carbapenem drug class • Concomitantly with valproic acid or divalproex sodium due to increased risk of breakthrough seizures due to significant reduction in valproic acid concentrations Dosing in Adults: • Standard dose: 4 gm (2 gm meropenem and 2 gm vaborbactam) IV over 3H Q8H for 14 days • Renal impairment dose adjustment for those with eGFR<50mL/min/1.73m2 -eGFR 30-49: 2gm Q8H -eGFR 15-29: 2gm Q12H -eGFR <15: 1gm Q12H -Hemodialysis: Adjust for renal function (e.g. 1gm Q12H). Give nearest dose after dialysis. Monitoring:

• SCr/BUN, CBC with differential at baseline and daily Considerations for Use:2 • Seizures and other adverse central nervous system (CNS) effects (e.g. delirium and/or headaches) have been reported in patients taking meropenem, a component of VabomereTM. Use with caution and monitor patients already diagnosed with a CNS disorder (e.g. history of seizures) • May have role in treatment of other infections caused by MDR gram-negative organisms. ID team must be consulted for all potential on and off label use. H= hour(s); ID= infectious diseases; Q= every; IV= Intravenous; eGFR= estimated glomerular filtration rate; CNS= central nervous system; gm= gram(s); mL= milliliters; min= minute(s); m= meters; KPC= Klebsiella pneumoniae carbapenemase producer; ESBL= extended-spectrum beta-lactamase producer; MBL= Metallo-beta-lactamase producer; MDR= multidrug resistant; CRE= carbapenem resistant Enterobacteriaceae; FDA= Food and Drug Administration; SCr= serum creatinine; BUN= blood urea nitrogen; CBC= complete blood count References: 1. Castanheira M, Huband MD, Mendes RE, et al. Meropenem-vaborbactam tested against contemporary gram-negative isolates collected worldwide during 2014, including carbapenem-resistant, KPC-producing, multidrug-resistant, and extensively drug-resistant enterobacteriaceae. Antimicrob Agents Chemother 2017; 61I(9):1-12. 2. Vabomere (Meropenem and Vaborbactam) [package insert]. The Medicines Company; Parsippany (NJ): August 2017.

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Oritavancin (Orbactiv®) Oritavancin (Orbactiv®) IV Only

Use requires formal ID Consult

Activity: Coverage against Staphylococcus aureus (MSSA and MRSA), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group and vancomycin-susceptible Enterococcus faecalis No clinical data, but activity in vitro vs. vancomycin-resistant enterococci and vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus Criteria for Use: • Treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive isolates • Unable to use vancomycin (due to intolerance, MIC >2, or infection unresponsive to vancomycin despite therapeutic concentrations) • Unable to use other agents (refer to empiric therapy for ABSSSI) Unacceptable Uses: • Patients with suspected osteomyelitis. If OM is suspected, alternative antibacterial therapy should be initiated • Contraindicated in patients with known hypersensitivity to oritavancin. Due to the possibility of cross-reactivity to glycopeptide, avoid in patients with previous glycopeptide hypersensitivity due to long half-life. Dosing in Adults: • Standard dose: 1200mg dose IV over 3 hours x1 • No renal or hepatic dose adjustment Monitoring: • SCr/BUN, AST, ALT, bilirubin, infusion-related reactions (pruritus, urticaria, flushing), hypersensitivity reactions, signs/symptoms of OM Considerations for Use: • The use of unfractionated heparin is contraindicated for 48 hours after oritavancin administration due to artificial prolongation of aPTT • Co-administration of oritavancin and warfarin may result in higher exposure of warfarin, which may increase the risk of bleeding • Oritavancin can artificially prolong aPTT for up to 120 Hr, and may prolong PT and INR for up to 12 Hr and ACT for up to 24 Hrs ABSSSI= acute bacterial skin and skin structure infections; ACT= Activated clotting time; ALT= Alanine aminotransferase; aPTT= Activated partial thromboplastin time; AST= Aspartate aminotransferase; BUN= Blood urea nitrogen; ID= Infectious Disease; INR= International normalized ratio; IV= Intravenous; MIC= Minimum inhibitory concentration; MRSA= Methicillinresistant Staphylococcus aureus; MSSA= Methicillin-susceptible Staphylococcus aureus; OM= osteomyelitis; PT= Prothrombin time; SCr= Serum creatinine

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Polymyxin Polymyxin B B IV Only

Use requires formal ID Consult

Polymyxin B and Colistin (also known as Polymyxin E or Colistimethate) are the two polymyxin antibiotics. Their spectrum of activity is similar. However, their pharmacology is very different. Polymyxin B is administered as the active drug and is not cleared renally. Colistin is a prodrug (Colistimethate sodium) and is cleared renally. The product vials may be labeled as International Units (IU) or mg. To avoid major dosing errors, carefully read vial labels. Recommend that all doses be converted to mg. Conversion: 10,000 International Units = 1 mg Activity: Coverage against most gram-negatives, including many multi-drug resistant (MDR) Enterobacteriaceae (such as E. coli, Klebsiella spp.; including ESBL-producing and carbapenem-resistant Enterobacteriaceae), Pseudomonas spp., and Acinetobacter spp. NOT ACTIVE against Proteus, Serratia, Providencia, Burkholderia, Stenotrophomonas, gram-negative cocci, gram-positive organisms, or anaerobes Criteria for Use: • Treatment of infections due to MDR Enterobacteriaceae, Pseudomonas spp., and Acinetobacter spp. with no other treatment options Unacceptable Uses: • Empiric treatment of suspected gram-negative infections • Monotherapy for serious infections due to rapid resistance development • Treatment of UTIs. Colistin preferred over polymyxin B for UTIs Dosing in Adults: Optimal dosing regimens are not well established • Standard dose: 2.5 mg/kg IV as a 2 hr infusion ONCE (load), then 12 hours later start 1.5 mg/kg IV as a 1 hr IV infusion. Repeat Q12H • No renal or hepatic dose adjustment • Use actual body weight for dosing • Caution in use > maximum product recommended daily dose (300mg) Monitoring: • BUN/ SCr at baseline and at least twice weekly Considerations for Use: • The most important side effect of IV polymyxin B is nephrotoxicity (20-40% of patients); less frequently reported concerns include neurotoxicity and neuromuscular blockade • Recent literature suggests that nephrotoxicity rates may be lower with polymyxin B as compared to colistin BUN= Blood urea nitrogen; ESBL= Extended spectrum beta-lactamase; H= hour(s); ID= Infectious Diseases; IU= international Units; IV= Intravenous; MDR= multi-drug resistant; Q= every; SCr= Serum creatinine; spp= Species; UTI= Urinary tract infection

PAGE 54

Colistin (Polymyxin or Colistimethate) Colistin (Polymyxin E or EColistimethate) IV Only

Use requires formal ID Consult

Colistin (also known as Polymyxin E or Colistimethate) and Polymyxin B are the two different polymyxin antibiotics. Colistin is a prodrug (Colistimethate sodium). The product vials may be labeled as International Units (IU) of prodrug, or mg of the active product: colistin base activity (CBA). To avoid major dosing errors, carefully read vial labels. Recommend that all doses be converted to mg of CBA. Conversion: 1,000,000 units of Colistimethate (prodrug) = 80 mg of Colistimethate (prodrug) = 30 mg of colistin base activity (CBA) Activity: Coverage against most gram-negatives, including many multi-drug resistant (MDR) Enterobacteriaceae (such as E. coli, Klebsiella spp.; including ESBL-producing and carbapenem-resistant Enterobacteriaceae), Pseudomonas spp., and Acinetobacter spp. NOT ACTIVE against Proteus spp., Serratia spp., Providencia spp, Burkholderia spp, Stenotrophomonas spp, gram-negative cocci, gram-positive organisms, or anaerobes Criteria for Use: • Treatment of infections due to MDR Enterobacteriaceae, Pseudomonas spp., and Acinetobacter spp. with no other treatment options • Treatment of UTI. Colistin preferred over polymyxin B for UTIs Unacceptable Uses: • Empiric treatment of suspected gram-negative infections • Use as monotherapy due to rapid resistance development Dosing in Adults: Optimal dosing regimens are not well established • Standard dose: 5 mg CBA/kg ONCE (load), then 2.5 mg CBA/kg Q12H • Renal dose adjustment: CrCl 20-50 mL/min: 5 mg CBA/kg ONCE (load), then 2.5 mg CBA/kg Q24H CrCl < 20 mL/min: 5 mg CBA/kg ONCE (load), then 2.5 mg CBA/kg Q48H Hemodialysis: 5 mg CBA/kg ONCE (load), then 30 mg CBA IV Q12H, AD • No hepatic dose adjustment • Use ideal body weight in obese patients for dosing • Caution in use > max product recommended daily dose (300 mg CBA) Monitoring: • BUN/ SCr at baseline and at least twice weekly Considerations for Use: • The most important side effect of IV colistin is nephrotoxicity (rates 50-60% of patients); less frequently reported concerns include neurotoxicity and neuromuscular blockade AD= After dialysis; BUN= Blood urea nitrogen; CBA= Colistin base activity; CrCl= Creatinine clearance; ESBL= Extended spectrum beta-lactamase; H= hour(s); ID= infectious diseases; IU= international units; IV= Intravenous; MDR= multi-drug resistant; Q= every; SCr= Serum creatinine; spp= species; UTI= Urinary tract infection

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Tedizolid (Sivextro®) Tedizolid (Sivextro®) IV and PO Only

Use requires formal ID Consult

Activity: Coverage includes Staphylococcus aureus (MSSA and MRSA), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Enterococcus faecalis (including VRE) Criteria for Use: • Treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive isolates • Unable to use vancomycin (due to intolerance, S. aureus MIC >2, or infection unresponsive to vancomycin despite therapeutic concentrations) • Unable to use other agents (refer to empiric therapy for ABSSSI) Unacceptable Uses: • Infections for other indications not listed above • Patients with neutropenia. Safety and efficacy in patients with neutrophil counts <1000 cells/mm3 have not been assessed. Decreased activity in the absence of granulocytes in animal models Dosing in Adults: • Standard dose: 200 mg IV/PO once daily for 6 days • No renal or hepatic dose adjustment • No dose adjustment is necessary when changing from IV to PO Monitoring: • CBC with differential Considerations for Use: • Tedizolid has been shown to be a reversible inhibitor of monoamine oxidase (MAO) in vitro, but no restrictions exist for concomitant use of drugs with serotonergic and adrenergic activity or tyramine containing foods. Of note, patients taking such medications were excluded from clinical trials. In vitro, in vivo, and clinical studies indicate weak MAO inhibition and a low potential for serotonergic adverse consequences • In phase 3 trials, reduction in hemoglobin, reduction in platelet count, and reduction in absolute neutrophil count were similar between tedizolid and linezolid • In phase 3 trials, adverse effects associated with neurologic and optic nerve disorders did not differ between tedizolid and linezolid ABSSSI= acute bacterial skin and skin structure infections; CBC= Complete Blood Count; ID= Infectious Disease; IV= Intravenous; MAO= monoamine oxidase; MIC= Minimum inhibitory concentration; MRSA= Methicillin-resistant Staphylococcus aureus; MSSA= Methicillin-susceptible Staphylococcus aureus; PO= By Mouth

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Tigecycline (Tygacil®) Tigecycline (Tygacil®) IV Only

Use requires formal ID Consult

Activity: Coverage against MRSA, VRE, most gram-negatives, and anaerobes NOT active against Pseudomonas aeruginosa or Proteus spp. Criteria for Use: • Alternative therapy in patients with mixed aerobic-anaerobic infections and severe allergy to beta-lactam agents, if VRE or MRSA are involved • Alternative therapy for patients with systemic infections due to ESBL-producing organisms (Klebsiella spp., E. coli) with severe allergies to first-line therapy (imipenem/cilastatin or meropenem) • Alternative therapy for selected isolates of Acinetobacter, Stenotrophomonas, and VRE • Treatment of documented VRE infections in patients unable to take linezolid Unacceptable Uses: • Treatment of P. aeruginosa or Proteus spp. infections • Urinary tract infections: low urinary concentrations • Bacteremia: Peak serum concentrations do not exceed 1 mcg/mL, which limits its use for treatment of bacteremia Dosing in Adults: • Standard dose: 100 mg IV load x1, then 50 mg IV Q12H (use higher doses for infections due to Acinetobacter and other MDR organisms) Infuse each dose over 30 to 60 minutes • No renal dose adjustment Supplemental dosing is not necessary following hemodialysis • Hepatic dose adjustment: Severe hepatic disease (Child Pugh C): 100mg IV load x1, then 25 mg IV Q12H Important Side Effects: • Nausea and vomiting (most common in first 1-2 days of therapy) • To minimize GI side effects avoid fasting state administration • Prolonging the infusion time (>1 hour) may make GI side effects worse • Shortening infusion time (<30 minutes) may increase the incidence of infusion related reactions (inflammation, pain, phlebitis, other) Management of tigecycline-induced nausea and vomiting: • Ondansetron (Zofran®): Single dose of 8-12 mg IV or 8-24 mg PO ESBL= Extended spectrum beta-lactamase; GI= Gastrointestinal; H= hour(s); ID= infectious diseases; IV= Intravenous; MDR= multidrug resistant; MRSA= Methicillin-resistant Staphylococcus aureus; PO= by mouth; Q= every; spp= species; VRE= Vancomycinresistant enterococci

PAGE 57

Liposomal Amphotericin B (L-AmB / AmBisome®) IV Only

Use requires formal ID Consult

Activity: Broad-spectrum antifungal activity with in vitro activity against Candida, Cryptococcosis, Aspergillus, Zygomycosis, and Fusarium Dosing of AmBisome and Amphotericin B deoxycholate is significantly different and NOT interchangeable. Do NOT use AmBisome doses for Amphotericin B deoxycholate and vice versa Criteria for Use: • Unable to use conventional amphotericin B deoxycholate due to: • Pre-existing renal insufficiency defined as SCr of ≥ 2 mg/dL or calculated CrCl of ≤ 25 mL/min, or SCr doubled from baseline • Refractory to or cannot tolerate conventional amphotericin B deoxycholate • SCr > 1.5 mg/dL and receiving concomitant cyclosporine or tacrolimus • Patients with irreversible ESRD on chronic HD or PD should receive amphotericin B deoxycholate Dosing in Adults: • Standard dose: • Febrile neutropenia: 3 mg/kg/day • May consider 5 mg/kg/day in patients with neutropenia > 10 days, evidence of fungal infection, or clinically unstable • Documented yeast (Candida spp., others) infection: 3-5 mg/kg/day • Documented mold (Aspergillus spp., others) infection: 3-5 mg/kg/day • Endopthalmitis: 5 mg/kg/day ± Flucytosine 25 mg/kg PO Q6H • Endocarditis: 5 mg/kg/day ± Flucytosine 25 mg/kg PO Q6H • Cryptococcal meningitis: 4 mg/kg/day ± Flucytosine 25 mg/kg PO Q6H • No renal/ hepatic dose adjustment • Administering 500mL to 1000mL of normal saline may decrease nephrotoxicity Monitoring: • BUN/SCr, K, Mg, Phos at baseline and daily in hospitalized patients; AST/ALT at baseline and every 1-2 weeks • Infusion related reactions such as fever, chills & myalgia are common • Consider premedication with diphenhydramine and/or acetaminophen • Consider infusing over 4 to 6 hours ALT= Alanine aminotransferase; AST= Aspartate aminotransferase; BUN= Blood urea nitrogen; CrCl= Creatinine clearance; ESRD= End-stage renal disease; H= hour(s); HD= Hemodialysis; ID= infectious diseases; IV= Intravenous; K= Potassium; Mg= Magnesium; PD= Peritoneal dialysis; Phos= Phosphorus; PO= by mouth; Q= every; SCr= Serum creatinine; spp= species

Caspofungin (Cancidas®) Caspofungin (Cancidas®) IV Only

Use Requires Formal ID Consult

Criteria for Use: Invasive Aspergillosis: • Patients refractory to or who cannot tolerate conventional amphotericin B deoxycholate, liposomal amphotericin B, voriconazole, or isavuconazole • Monotherapy is not routinely recommended and should be given in combination with voriconazole or amphotericin B in patients with documented invasive aspergillosis Systemic Candida infections: • Systemic Candida infections secondary to C. glabrata or C. kruseii and other non-Candida albicans (pending fluconazole susceptibility testing) • Patients unable to tolerate conventional amphotericin B or patients with concomitant renal insufficiency as per liposomal amphotericin B guidelines • Patients unable to tolerate fluconazole as defined by a serious rash, tripling of baseline LFTs, or other adverse reaction • Empiric use until non-albicans is confirmed Dosing in Adults: • Standard dose: 70 mg IV x1, then 50 mg IV Q24H • No renal dose adjustment • Hepatic dose adjustment: Moderate hepatic impairment: 70 mg IV x1, then 35 mg IV Q24H • Patients receiving rifampin or phenytoin: Consider 70 mg IV Q24H (due to enzyme induction effect) Monitoring: • Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) at baseline and weekly ALT= Alanine aminotransferase; AST= Aspartate aminotransferase; H= hour(s); ID= infectious diseases; IV= Intravenous; LFTs= Liver Function Tests; PO= by mouth; Q= every

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Isavuconazonium sulfate (Cresemba®) Isavuconazonium sulfate (Cresemba®) IV and PO Only

Use requires formal ID Consult

Activity: Coverage against most strains of the following microorganisms, both in vitro and in clinical infections: Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, and Mucorales such as Rhizopus oryzae, Mucormycetes species, Candida albicans, and most Candida non-albicans Criteria for Use: • Treatment of invasive aspergillosis • Treatment of invasive mucormycosis Unacceptable Uses: • Treatment for other fungal infections (Blastomyces, Histoplasma, etc.) • Contraindicated with known hypersensitivity to isavuconazole. Caution in use in patients with hypersensitivity to other azoles • Contraindicated in patients with familial short QT syndrome (shortens the QTc interval in a concentration-related manner) Dosing in Adults: • Standard dose: 372 mg IV/PO Q8H x 6 doses (48 hours; load), then 372 mg Q24H starting 12-24 hours after last loading dose • No renal or hepatic dose adjustment • IV must be administered via an infusion set with in-line filter (pore size 0.2-1.2 micron) and should be infused over a minimum of 1 hour • Flush line with NS or D5W before and after infusion • No dose adjustment is necessary when changing from IV to PO Monitoring: • AST/ALT/bilirubin at baseline and every 1-2 weeks after Considerations for Use: • Elevated LFTs have been reported in clinical trials. Elevations generally reversible and do not require discontinuation • May cause fetal harm when administered to a pregnant woman Important note regarding drug interactions: • Isavuconazole is a substrate/inhibitor of CYP3A4 and has multiple drug interactions that may affect its levels and/or those of co-administered drugs. Dose adjustment may be necessary • Some drugs with interactions of major significance include: − Carbamazepine − Cyclosporine − Rifampin/rifabutin − Warfarin − Ritonavir − Tacrolimus − Sirolimus − Phenytoin ALT= Alanine aminotransferase; AST= Aspartate aminotransferase; H= hour(s); ID= infectious diseases; IV= Intravenous; LFT’s= Liver Function Tests; PO= by mouth; Q= every

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Voriconazole (V-Fend®) Voriconazole (V-Fend®) IV and PO Only

Use requires formal ID Consult

Activity: Coverage against most Candida spp., except C. glabrata which may be S-DD or resistant. Does not cover zygomycoses (Mucor, Rhizopus, Cunninghamella, etc.). Criteria for Use: • Treatment of documented invasive aspergillosis • Can be used in combination with caspofungin in microbiologically or radiographically confirmed Aspergillus • Serious mycosis infections due to Fusarium spp., Scedosporium apiospermum Dosing in Adults: • Standard dose: IV: 6 mg/kg IV x2 doses (load), then 4 mg/kg IV Q12H • IV voriconazole should be avoided in patients with CrCl < 50 mL/min due to accumulation of cyclodextran vehicle (excipient) • Patients tolerating PO medications, should be given orally Voriconazole oral formulation is >95% bioavailable PO: 400 mg PO x2 doses (load), then 200 mg PO Q12H • Oral formulation may be used without dose adjustment • Hepatic dose adjustment: Mild to Moderate hepatic impairment: Standard loading dose, but half maintenance dose (IV: 2 mg/kg IV Q12H; PO: 100mg PO q12H) Monitoring: • Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT)/ bilirubin at baseline and every 1-2 weeks after • Serum trough levels: Draw first level within 2 to 5 days of initiating therapy and regularly thereafter. Also check when changing from IV to PO since this agent does not demonstrate linear pharmacokinetics • Goal level between 2 and 5 mcg/mL • Levels > 5 or 6 mcg/mL are associated with toxicities including visual disturbances, liver dysfunction, skin reaction, neurotoxicity (confusion, hallucinations) Important note regarding drug interactions: • Voriconazole has multiple drug interactions that may affect its levels and/or those of co-administered drugs. Dose adjustment may be necessary •

Some drugs with interactions of major significance include: − Carbamazepine − Tacrolimus − Rifampin/rifabutin − Cyclosporine − Ritonavir − Warfarin − Sirolimus − Phenytoin

ALT= Alanine aminotransferase; AST= Aspartate aminotransferase; CrCl= Creatinine Clearance; H= hour(s); ID= infectious diseases; IV= Intravenous; mcg= micrograms; mL= milliliter; PO= by mouth; Q= every; S-DD= susceptible dose-dependent; spp= species

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Bezlotoxumab (ZinplavaTM) Bezlotoxumab (Zinplava™) IV Only

Use requires formal ID Consult

Monoclonal antibody targeting Clostridium difficile toxin B. Adjunctive therapy for patients with C. difficile infection (CDI) on treatment and at high risk for recurrence. Criteria for Use (must meet all of the following for eligibility): • Receiving standard therapy for recurrent CDI: vancomycin PO or fidaxomicin • Documented CDI with both diarrhea (at least 3 loose stools in a 24 hour period) in addition to a positive C .difficile toxin test in the past 7 days • Recurrence of CDI with prior receipt > 2 completed courses of oral vancomycin (including a tapered or pulse regimen) or fidaxomicin within the prior 6 months • Currently hospitalized or eligible to receive in an ambulatory infusion clinic Unacceptable Uses: • Fulminant CDI (e.g. life-threatening CDI or toxic mega-colon) • Known hypersensitivity to bezlotoxumab • History of congestive heart failure unless the benefits outweigh the risks (increased mortality versus placebo group in a clinical trial) • Active diarrheal illness such as, but not limited to, colitis or Crohn’s disease Dosing and administration in Adults: • 10 mg/kg (based on actual body weight) in 250 ml NS or D5W as an intravenous infusion over 60 minutes (Note: volume can be decreased to 200 ml in patients where volume is a concern) • Should be administered with a 0.22-5 micron in-line or add-in filter • Can be given via peripheral or central venous catheter • Do not administer other drugs simultaneously through the same infusion line Monitoring: • Adequate monitoring of infusion reactions must performed Considerations for Use: • Relapse data on fidaxomicin with bezlotoxumab is limited. • Phase 3 trials had fewer patients treated with fidaxomicin versus vancomycin • Patients with chronic diarrheal illness, such as inflammatory bowel disease, were excluded from clinical trials. Benefit in this population is unknown. • Patients should not donate blood within 6 months following infusion • Antiperistaltic agents, such as diphenoxylate/atropine sulfate, at any time during the 14 days following the infusion should be avoided • Based on clinical trial the following are considered high-risk for CDI recurrence: • Age ≥ 65 years • Antibiotics in the last 12 weeks Zar Score:* • ≥ 1 CDI episode(s) in last six months • 1 pt for: >60 years of age, • ≥ 2 CDI episodes ever temperature >100°F, albumin <2.5 g/dl, WBC >15 within 48 hrs • Immunocompromised • 2 pts for: pseudomembranous • Severe CDI defined as a Zar score ≥ 2 colitis, ICU level of care • Hypervirulent CDI strain Zinplava (bezlotoxumab) [package insert]. Merck and Co., Inc; Whitehouse Station (NJ): 2016. Wilcox MH, Gerding DN, Poxton IR, et al. N Engl J Med. 2017 Jan 26;376(4):305-317.

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1.25g q24h

1.5g q24h

1.25g q24h

1.5g q24h

≥100

1.25g q24h

1g q24h

1g q8h

1.25g q12h

1g q12h

750mg q12h

500mg q12h

Contact Antimicrobial Stewardship Team

1.25g q24h

1g q24h

1.25g q24h

1g q24h

750mg q24h

500mg q24h

1g q24h

500mg q24h 500mg q24h 500mg q24h 750mg q24h 750mg q24h

CrCl (mL/min) Weight (kg)

Vancomycin Dosing Nomogram

1g q8h

1.5g q8h

1.25g q8/12h

1g q8/12h

500mg q8/12h 500mg q8/12h 500mg q8/12h 750mg q8/12h 750mg q8/12h 750mg q8/12h

1.5g q8h

1.25g q8h

1.25g q8/12h

1g q8/12h

500mg q8/12h 500mg q8/12h 500mg q8/12h 750mg q8/12h 750mg q8/12h 750mg q8/12h

≥100

1.5g q8h

1.25g q8h

1g q8h

750mg q8h

500mg q8h

If Patient is obese: 30mg/kg/day in divided doses q8h

1.25g q12h

1g q12h

750mg q12h

500mg q12h

1.25g q12h

1g q12h

750mg q12h

500mg q12h

Cr Cl in mL/min

Vancomycin Dosing Nomogram

weight in kg

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Guidelines Guidelines for Vancomycin Dosing and Determination for Vancomycin Dosing Determination of Trough Trough Levels Levels in in Guidelines for Vancomycin Dosing and and Determination of Adult Patients Levels in Adult Patients Patients Adult of Trough

Refer Refer to to Vancomycin Vancomycin Dosing Dosing Nomogram Nomogram OR OR calculate calculate dose dose as as described described below: below: I. How to calculate a vancomycin dose: I. How to calculate a vancomycin dose: a) a) Obtain Obtain actual actual body body weight weight (ABW) (ABW) NOTE: NOTE: do do not not calculate calculate dose dose based based on on lean lean body body weight; weight; if if morbidly morbidly obese obese use use ABW ABW for for initial initial loading loading dose dose and and monitor monitor trough trough or or consult consult ID. ID. b) b) Loading Loading Dose Dose (LD): (LD): For For more more severe severe infections infections (i.e., (i.e., Meningitis, Meningitis, endocarditis, endocarditis, pneumonia, etc.) consider a loading dose of 25-30 mg/kg pneumonia, etc.) consider a loading dose of 25-30 mg/kg ABW ABW LD LD == 25-30 25-30 mg/kg mg/kg (Use (Use ACTUAL ACTUAL body body weight) weight) c) c) Maintenance Maintenance dose dose (MD): (MD): Calculate Calculate each each maintenance maintenance dose: dose: MD = 15 mg/kg (Use ACTUAL body weight) MD = 15 mg/kg (Use ACTUAL body weight) d.) d.) Special Special Populations: Populations: Morbid 130% of of IBW) IBW) use use 30 30 mg/kg/day mg/kg/day divided divided Q8H Q8H as as obese obese Morbid obesity obesity (≥ (≥ 130% 1,2,3 Obese patients Q8H)1,2,3 patients often often require require more more frequent frequent dosing dosing intervals intervals (i.e., (i.e., Q8H) Obese patients patients rarely rarely need need doses doses in in excess excess of of 3.5 3.5 gm gm per per day. day. Suggest Suggest starting starting at at 1 1 to 1.25 1.25 gm gm Q8H Q8H and and adjust adjust upward upward if if necessary. necessary. to Round doses should should be be rounded rounded to to the the nearest nearest 250 250 mg mg Round calculated calculated dose: dose: doses increment (i.e., 500 mg, 750 mg, 1000 mg, 1250 mg, 1500 mg, etc.) increment (i.e., 500 mg, 750 mg, 1000 mg, 1250 mg, 1500 mg, etc.) II. Estimate patient’s creatinine creatinine clearance clearance (CrCl) (CrCl) II. Estimate patient’s Use the the Cockcroft-Gault Cockcroft-Gault equation. equation. (See (See Pharmacokinetic Pharmacokinetic Section Section for for equation) equation) Use III. Select Select dosing dosing interval interval based based on on CrCl CrCl III. Estimated CrCl CrCl (mL/min) (mL/min) Estimated ≥100 ≥100

Dosing interval interval to to consider consider Dosing Q8H Q8H

80-99 80-99 50-79 50-79

Q8H Q8H or or Q12H Q12H Q12H Q12H

25-49 25-49 <25 <25 mL/min mL/min Hemodialysis Hemodialysis (check (check pre-dialysis pre-dialysis level) level)

Q18H Q18H or or Q24H Q24H Q36H Q36H or or Q48H Q48H

Peritoneal Peritoneal dialysis dialysis (IV (IV administration) administration)

Give an an initial initial loading loading dose dose of of Give 15-20 15-20 mg/kg mg/kg Re-dose Re-dose patient patient with with 15 15 mg/kg mg/kg when when serum serum level ≤ 20 mcg/mL level ≤ 20 mcg/mL

If If the the estimated estimated renal renal function function (CrCl) (CrCl) is is near near the the border border of of two two dosing dosing intervals, intervals, it it may may be be reasonable to to begin reasonable begin with with the the more more aggressive aggressive interval; interval; the the dose dose can can then then be be modified modified if if necessary levels. necessary according according to to serum serum levels.

ABW= Actual Actual body body weight; weight; CrCl= CrCl= Creatinine Creatinine clearance; clearance; H= H= hour(s); hour(s); IBW= IBW= ideal ideal body body weight; weight; ID= ID= infectious infectious diseases; diseases; LD= LD= loading loading ABW= dose; dose; MD= MD= maintenance maintenance dose; dose; Q= Q= every every References: References: 1. Bauer LA, Black DJ, Lill JS. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol. 1998 Oct;54(8):621-5. 1. Bauer LA, Black DJ, Lill JS. Vancomycin dosing in morbidly obese patients. Eur J Clin Pharmacol. 1998 Oct;54(8):621-5. 2. Vance-Bryan K, Guay DR, Gilliland SS, et al. Effect of obesity on vancomycin pharmacokinetic parameters as determined by using a Bayesian 2. Vance-Bryan K, Guay DR, Gilliland SS, et al. Effect of obesity on vancomycin pharmacokinetic parameters as determined by using a Bayesian forecasting technique. Antimicrob Agents Chemother. 1993 Mar;37(3):436-40. forecasting technique. Antimicrob Agents Chemother. 1993 Mar;37(3):436-40. 3. Blouin RA, Bauer LA, Miller DD, et al. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother. 3. Blouin RA, Bauer LA, Miller DD, et al. Vancomycin pharmacokinetics in normal and morbidly obese subjects. Antimicrob Agents Chemother. 1982 Apr;21(4):575-80. 1982 Apr;21(4):575-80.

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Guidelines Guidelines for Vancomycin Dosing and Determination for Vancomycin Dosing and Determination of Trough Levels in Adult of Trough Patients Levels in Adult Patients IV. Vancomycin Levels Vancomycin levels are NOT needed in patients with stable renal function who are on standard doses of vancomycin AND are on therapy for less than 5 days. Vancomycin peak levels are rarely, if ever, indicated. NOTE: Vancomycin demonstrates concentration-independent killing; therefore, peak concentrations are NOT useful or correlated to clinical outcomes. Measure Trough Concentrations Only if:  Patient is receiving vancomycin therapy > 5 days  Patient has unstable renal function  Patient is on an unusual/aggressive dosing regimen  Patient is morbidly obese (> 130% of IBW)  Patient has severe or life threatening infection and is receiving concomitant nephrotoxic drugs (i.e., cyclosporine, amphotericin B, aminoglycosides) V. Implications for NURSING Vancomycin needs to accumulate (steady state concentration) in order to obtain an accurate concentration. Please DO NOT order a plasma level unless 3 doses have been administered on a given schedule (i.e., order trough prior to the 4th dose) Exception: Dosing interval of 24 hours or longer Trough level should be drawn within 30 minutes of the next dose • Check what time the previous vancomycin dose (prior to the trough) was administered • Calculate how many hours are between the dose and level • Interpret the level in the context of recent vancomycin doses Example: If the patient is on 1gm Q12H and received a dose at 11pm, then a level taken at 6am is 7 hours post-dose and is NOT a trough level. • Be careful NOT to adjust OR hold vancomycin doses based on incorrectly drawn levels • Do NOT hold the next dose while waiting for trough results (sub-therapeutic levels <15mcg/mL are not effective and can lead to resistant pathogens) H= hour(s); IBW= Ideal body weight; Q= every

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Guidelines Guidelines for Vancomycin Dosing and Determination for Vancomycin Dosing and Determination of Trough Levels in Adult of Trough Patients Levels in Adult Patients VI. Target Trough Vancomycin Level Type of Infection

Target Trough Vancomycin Level

MRSA pneumonia, CNS infection (meningitis), bacteremia, endocarditis, osteomyelitis

15-20 mcg/mL

Endovascular Infection

15-20 mcg/mL

Hemodialysis Serious infection and renal dysfunction (CrCl < 25mL/min)

Maintain 15-20 mcg/mL Check pre-dialysis level, re-dose when ≤ 20 mcg/mL Often recommend to load with 15 – 20 mg/kg and re-dose If ≥ 24H dosing check trough at 24 hours Maintain 15-20 mcg/mL

VII. Adjusting a vancomycin dose (Recommendations) Trough is too low- change the interval, keep the dose • If the level is < 5 mcg/mL, the dosing INTERVAL should be shortened Example: Trough level after 5 days of treatment reported as 3 mcg/mL on a regimen of 1000 mg Q12H, the interval should be shortened to 1000 mg Q8H Trough is too high- decrease the dose, keep the interval • If the trough level is >25 mcg/mL, the DOSE should be decreased 50% Example: Trough level after 5 days of treatment is reported as 29 mcg/mL on a regimen of 1000 mg Q12H; the dose should be decreased to 500 mg Q12H VIII. Monitoring (Inpatient) • Baseline weight, BUN, serum creatinine, WBC, temperature, cultures, and sensitivities should be taken every other day in stable patients • Daily urinary IN’s and OUT’s, CBC, and temperature should be monitored; should be performed in patients admitted to the ICU BUN= Blood urea nitrogen; CBC= Complete Blood Count; CNS= Central nervous system; CrCl= Creatinine clearance; H= hour(s); ICU= Intensive Care Unit; MRSA= Methicillin-resistant Staphylococcus aureus; Q= every; WBC= White blood cells

PAGE 66

Guidelines Guidelines for Administration of High for Administration of High Dose Once Daily Dose Aminoglycosides Once Daily (HDOD) Aminoglycosides (HDOD) High Dose Once Daily Aminoglycosides (HDOD) are considered safe and effective in patients with stable renal function Exclusion Criteria for HDOD: If patients fall into the following categories, use traditional/conventional dosing since there is limited data using HDOD in the following patient populations Acute renal failure OR CrCl < 20 mL/min Half-life (t1/2) ≥ 4 hours Dialysis

Age < 18 OR > 90 Severe burns Ascites

To use Traditional Dosing Methods, see www.globalrph.com “medical calculator”

II.

For AMG dosing, contact the Antimicrobial Stewardship team or follow the steps below: Calculate the patient’s Ideal Body Weight (IBW) Male: 50 kg + [2.3 kg for each inch over 5 feet] Female: 45 kg + [2.3 kg for each inch over 5 feet] Determine the dose based on the table below (round dose to the nearest 20 mg) Aminoglycoside

Tobramycin Gentamicin

Maintenance Dose 5 mg/kg (IBW) 5 mg/kg (IBW)

• Dose is based on IBW except in obese patients OR those under their IBW • Use ABW if patient weight is less than IBW • Use AdjBW in patients who are obese (≥ 130% of IBW) Adjusted Body Weight (AdjBW) Calculation AdjBW = 0.4 (ABW – IBW) + IBW III.

Estimate the patient’s creatinine clearance (CrCl) using the Cockcroft and Gault equation (refer to Pharmacokinetic Section)

IV.

Select dosing interval based on calculated CrCl from the tables below: CrCl (mL/min)

Estimated Dosing Interval

≥ 60

Every 24 hours

40–59 20–39

Every 36 hours Every 48 hours

≤ 20

Use traditional dosing method, see www. Globalrph.com “medical calculator”

ABW= Actual Body Weight; AdjBW= Adjusted Body Weight; AMG= aminoglycosides (i.e., gentamicin and tobramycin); CrCl= Creatinine clearance; HDOD= High Dose Once Daily Aminoglycosides; IBW= Ideal Body Weight (in kg); t1/2= half life

PAGE 67

Guidelines Guidelines for Administration of High for Administration of High Dose Once Daily Dose Aminoglycosides Once Daily (HDOD) Aminoglycosides (HDOD) V.

Commonly Targeted Peak and Trough Concentrations in HDOD

Disease State

Cystitis Gram-Positive Synergy Pyelonephritis Pneumonia

Gentamicin/Tobramycin

Amikacin

Recommended Peak (mcg/mL)

Estimated mg/kg (IBW)

Recommended Peak (mcg/mL)

Estimated mg/kg (IBW)

6–8

2–3

30-40

10–15

6–8

2–3

30–40

10–15

12–14

3–4

60–70

16–20

5–6

60–80

20–25

Sepsis

10–12

3–4

60–70

Intra-abd/SSTI

12–16

4–5

60–70

Clinical Considerations

VI.

Trough should not exceed 0.3 mcg/mL

Trough should not exceed 1 mcg/mL

Monitoring of serum levels and dosage adjustments a. First-dose levels are NOT routinely needed  First-dose levels may be indicated in patients with variable volume of distribution or unstable renal function (sepsis or post-operatively) to assess clearance b. Serum levels should be performed routinely by day 3 of therapy only once it has been determined that aminoglycoside therapy is to continue  Example: empiric therapy for sepsis from a UTI awaiting culture results does not require peak/trough levels c. Peak and trough serum levels: 1–2 hours post-end of infusion (peak) and immediately prior to the next dose  Document actual time medication was hung  Obtain peak level 1-2 hour post infusion (very important for distribution phase); 2 hr preferred if dose > 400 mg  Use pharmacokinetic formulas (or www.globalrph.com “medical calculator”), to extrapolate peaks and troughs  Extrapolated trough concentrations should not exceed 0.30 mg/mL  Dosage or interval adjustments should be made at this time d. Once stabilized, if therapy is to continue > 1 week, obtain the following laboratory values:  SCr and BUN levels to monitor renal function (every other day)  Peak and trough levels (efficacy and no toxicity), twice per week e. If there is a suggested change in renal function OR other nephrotoxic agents (e.g., cisplatin, amphotericin B, pentamidine, vancomycin) are being used concurrently, more frequent levels of BUN, SCr, and monitoring may be necessary

BUN= Blood urea nitrogen; HDOD= high dose once daily; IBW= ideal body weight; SCr= Serum creatinine; SSTI= skin and soft tissue infection; UTI= Urinary tract infection

PAGE 68

Antimicrobial Dosing Guidelines for Adult Patients Based on Renal Function CRCL (ML/MIN) ACYCLOVIR IV >50 30-50 10-29 <10

STANDARD DOSE 5 mg/kg Q8H 5 mg/kg Q12H 5 mg/kg Q24H 2.5 mg/kg Q24H

MAXIMAL DOSE 10 mg/kg Q8H* 10 mg/kg Q12H* 10 mg/kg Q24H* 5 mg/kg Q24H*

HD D

Dose using ideal body weight *Use maximum dose for meningitis/encephalitis and varicella in immunocompromised host

AMOXICILLIN PO > 30 10-29 <10 AMOXICILLIN/CLAVULANATE PO > 30 10-29 <10

250 mg Q8H 250 mg Q12H 500 mg Q24H

500 mg Q8H 500 mg Q12H 500 mg Q24H

500 mg Q8-12H* 500 mg Q12H 500 mg Q24H

875 mg Q12H 875 mg Q12H 875 mg Q24H

1 gm Q4-6H 1 gm Q8H 1 gm Q12H 1 gm Q24H

2 gm Q4-6H* 2 gm Q6-8H 2 gm Q8-12H 2 gm Q24H

1.5 gm Q6H 1.5 gm Q8H 1.5 gm Q12H 1.5 gm Q24H

3 gm Q6H* 3 gm Q8H* 3 gm Q12H* 3 gm Q24H*

*Use 500 mg Q8H for osteomyelitis for CrCl â&#x2030;¥ 30 mL/min

AMPICILLIN IV >50 30-50 10-29 <10

*Use 2 gm Q4H for meningitis

AMPICILLIN/SULBACTAM IV >50 30-50 10-29 <10

*Use 3 gm if penetration is an issue (abscess/diabetic foot /vascular insufficiency/ osteomyelitis/intra-abdominal)

AZTREONAM IV >50 30-50 10-29 <10 CEFAZOLIN IV >50 30-50 10-29 <10

1 gm Q8H 1 gm Q12H 1 gm Q24H 500 mg Q24H

2 gm Q6H 1 gm Q8H 1 gm Q12 1 gm Q24H

1 gm Q8H 1 gm Q8H 1 gm Q12H 1 gm Q24H (2gm

2 gm Q8H 2 gm Q8H 2 gm Q12H 2 gm Q24H

Q48H)

Dosing Guidelines for Adult Patients Antimicrobial Antimicrobial Dosing Guidelines for Adult onBased Renalon Function Based Patients Renal Function CRCL (ML/MIN)

CEFEPIME IV >50 30-50 10-29 <10

STANDARD DOSE

MAXIMAL DOSE

1 gm Q12H 1 gm Q24H 1 gm Q24H 0.5-1 gm Q24H

2 gm Q12H 2 gm Q24H 1 gm Q24H 1 gm Q24H

100 – 200 mg Q12H 100 – 200 mg Q24H 100 – 200 mg 3 times per week

400 mg Q12H 400 mg Q24H 400 mg 3 times per week

250 mg Q12H 250 mg Q24H

500 mg Q12H 500 mg Q24H

1 gm Q24H No Change

2 gm Q24H* No Change

Pseudomonal Coverage or Febrile Neutropenia: >50: 2gm Q8H; 30-50: 2gm Q12H; 10-29: 1gm Q12H; < 10: 1gm Q24H

CEFPODOXIME PO ≥30 <30 HD CEFUROXIME PO ≥20 < 20 CEFTRIAXONE IV >50 <50-5 (INCLUDING HD)

*All indications are dosed at 1gm Q24H with the exception of meningitis (2 gm Q12H) and osteomyelitis (2 gm Q24H)

CEPHALEXIN PO >30 10-29 <10 CIPROFLOXACIN IV >30 10-29 <10

250 mg Q6H 250 mg Q8H 250 mg Q12H

500 mg Q6H 500 mg Q8H 500 mg Q12H

400 mg Q12H* 400 mg Q24H 400 mg Q24H

400 mg Q8H* 400 mg Q12H 400 mg Q24H

500 mg Q12H 500 mg Q24H 250 mg Q24H

750 mg Q8H 750 mg Q12H 500 mg Q24H

600 mg Q8H No Change

900 mg Q8H No Change

300 – 450 mg Q8H No Change

450 mg Q6H No Change

*Use Q8H dosing only for Pseudomonas aeruginosa

CIPROFLOXACIN PO >30 10-29 <10 CLINDAMYCIN IV >50 <50 CLINDAMYCIN PO >50 <50

PAGE 69

Dosing Guidelines for Adult Patients Antimicrobial Antimicrobial Dosing Guidelines for Adult onBased Renalon Function Based Patients Renal Function CRCL (ML/MIN)

DICLOXACILLIN PO >50 <50 DOXYCYCLINE PO >50 <50 FLUCONAZOLE IV/PO* >30 10-29 <10

STANDARD DOSE

MAXIMAL DOSE

250 – 500 mg Q6H No Change

100 mg Q12H No Change

200 mg Q24H 100 mg Q24H 100 mg Q48H

400 mg Q24H** 200 mg Q24H 200 mg Q48H

2.5-5*mg/kg Q24H 1.25 mg/kg Q24H 0.625 mg/kg Q24H 0.625 mg/kg Q48H

5 mg/kg Q12H 2.5 mg/kg Q24H 1.25 mg/kg Q24H 1.25 mg/kg Q48H

HD ND

*RECOMMENDATIONS FOR SYSTEMIC INFECTION ONLY, NOT FUNGURIA. Give PO if patient has functioning GI tract **May require dosages up to 800 mg/d depending on Candida species/sensitivities

GANCICLOVIR IV >50 30-50 10-29 <10

*5 mg/kg for CrCl ≥70 mL/min, 2.5 mg/kg for CrCl 50-69 mL/min

GANCICLOVIR PO >50 30-50 10-29 <10 IMIPENEM/CILASTATIN >50 30-50 10-29 <10

1 gm Q8H 1-1.5 gm Q24H 500 mg Q24H 500 mg Q48H

500 mg Q6H 500 mg Q8H 500 mg Q12H 250 mg Q12H

1 gm Q6H* 500 mg Q6H* 500 mg Q8H* 500 mg Q12H*

1 gm Q8H 1 gm Q12H 500 mg Q12H 500 mg Q24H

2 gm Q8H 1 gm Q8H 1 gm Q12H 1 gm Q24H

For suspected pseudomonas or ESBL infection use max doses

MEROPENEM IV > 50 26 – 50 10 – 25 <10 OR HD*

*If patient on HD schedule daily dose to be administered immediately after dialysis.

METRONIDAZOLE IV/PO* >10 <10

500 mg Q8H 500 mg Q12H

*No indication for Q6H dosing PAGE 70

DosingGuidelines Guidelinesforfor Adult Patients Antimicrobial Antimicrobial Dosing Adult onBased Renalon Function Based Patients Renal Function CRCL (ML/MIN) MOXIFLOXACIN IV/PO >50 <50 NAFCILLIN/OXACILLIN >50 <50-5 (Including HD) NITROFURANTOIN* >50 <50

STANDARD DOSE

MAXIMAL DOSE

400 mg Q24H No Change

1 gm Q4H No Change

2 gm Q4H No Change

100 mg Q12H Not Recommended

N/A

*Do not use in systemic infections. Drug is ineffective with CrCl < 40mL/min due to inadequate urinary concentrations.

OSELTAMIVIR PO > 60 >30-60 >10-30 PIPERACILLIN/TAZOBACTAM* >50 30-50 10-29 <10

75 mg Q12H 30 mg Q12H 30 mg Q24H

3.375 gm Q6H 3.375 gm Q6H 3.375 gm Q8H 3.375 gm Q12H

3.375 gm Q4H 3.375 gm Q6H 3.375 gm Q6H 3.375 gm Q8H

10 mg/kg Q24H 10 mg/kg Q24H

10 mg/kg Q12H 10 mg/kg Q24H

Non-PCP 2.5 mg/kg Q12H 2.5 mg/kg Q12H 2.5 mg/kg Q12H 2.5 mg/kg Q24H

PCP 5 mg/kg Q6H 5 mg/kg Q6H 5 mg/kg Q12H 5 mg/kg Q24H*

N/A

*Use for maximal dose for empiric therapy or treatment of Pseudomonas aeruginosa. If polymicrobial infection without P. aeruginosa is suspected, consider using ampicillin/sulbactam

RIFAMPIN PO >10 <10 SULFAMETHOXAZOLE/ TRIMETHOPRIM IV >50 30-50 10-29 <10

N/A

Dosing based on trimethoprim (TMP) component. *Avoid if possible, not recommended by manufacturer for CrCl <15 mL/min due to nephrolithiasis.

PAGE 71

Dosing Guidelines for Adult Patients Antimicrobial Antimicrobial Dosing Guidelines for Adult onBased Renalon Function Based Patients Renal Function CRCL (ML/MIN)

SULFAMETHOXAZOLE/ TRIMETHOPRIM PO >50 30-50 10-29* <10*

STANDARD DOSE

MAXIMAL DOSE

(Equal to IV Dose)

1-2 DS Q8-12H 1-2 DS Q12H 1-2 DS Q12H* 1-2 DS Q24H*

5 mg/kg Q6H 5 mg/kg Q6H 5 mg/kg Q12H* 5 mg/kg Q24H*

Dosing based on trimethoprim (TMP) component. Round to the nearest 160 mg of TMP component. *Not recommended by manufacturer for CrCl <15 mL/min due to nephrolithiasis

VANCOMYCIN PO ** >50 <50

125 mg Q6H No Change

**For C. difficile only in patients with sdevere disease or failed metronidazole therapy *For IV dosing see vancomycin dosing guidelines

Dosing based on Cockcroft and Gault Equation

D= Dialyzed 50 – 100%; HD= Hemodialysis; MD= Moderately dialyzed 20-49%; N/A= No information available; ND= Not dialyzed 0-5%

PAGE 72

Antimicrobial Duration of Therapy Antimicrobial Duration of Therapy INFECTIOUS DISEASE

Clostridium difficile Mild-moderate (initial episode) Severe, uncomplicated (initial episode) First recurrence (based on severity)

RECOMMENDED DURATION OF THERAPY

STRENGTH OF RECOMMENDATION

10 – 14 days (vancomycin) 10 – 14 days (vancomycin)

A-I B-I

10 – 14 days

A-II (C-III)

5 days (may require additional therapy depending on patient’s response)

7-14 days (based on patient’s response)

7 days if prompt resolution of symptoms OR 10-14 days for delayed clinical response

A-III

5 days if using levofloxacin in a patient who is not seriously ill

B-III

3 days in a female ≤ 65 years old without upper urinary tract symptoms after catheter has been removed

B-II

Asymptomatic bacteriuria in a pregnant female

3 -7 days

A-III

Acute uncomplicated cystitis in an adult female

Nitrofurantoin: 5 days Trimethoprim-sulfamethoxazole: 3 days Fosfomycin: 1 dose

A-I A-I A-I

4-7 days

A-III

Acute stomach and proximal jejunal perforations where source control is achieved within 24 hours, in the absence of acid-reducing therapy or malignancy

24 hours of therapy

B-II

Acute appendicitis without evidence of perforation, abscess, or local peritonitis

≤24 hours

A-I

Bowel injuries attributable to penetrating, blunt, or iatrogenic trauma that are repaired within 12h and any other intraoperative contamination of the operative field by enteric contents

≤24 hours

A-I

Skin and Skin Structure Uncomplicated cellulitis Complicated MRSA (deeper soft tissue infections, surgical/traumatic wound infection, major abscesses, cellulitis, and infected ulcers and burns) Genitourinary Catheter-associated urinary tract infection

Intra-abdominal Established intra-abdominal infection where source control is achieved

MRSA= Methicillin-Resistant S. aureus; NA= not applicable

PAGE 73

Antimicrobial of Antimicrobial Duration of Therapy Antimicrobial Duration Duration of Therapy Therapy INFECTIOUS DISEASE INFECTIOUS DISEASE

Pneumonia Pneumonia Community-acquired pneumonia Community-acquired pneumonia

Hospital-acquired pneumonia Hospital-acquired pneumonia (HAP) and ventilator-associated (HAP) and ventilator-associated pneumonia (VAP) pneumonia (VAP)

Diabetic Foot Diabetic Foot General recommendation General recommendation

Specific situations: Specific situations: Mild DFI Mild DFI Moderate to severe DFI Moderate to severe DFI (without osteomyelitis) (without osteomyelitis) Diabetic Foot Infection with Diabetic Foot Infection with Osteomyelitis Osteomyelitis Catheter-related Bloodstream Catheter-related Bloodstream Infections (CRBSI) Infections (CRBSI) Uncomplicated CRBSI due to Uncomplicated CRBSI due to coagulase negative staphylococci coagulase negative staphylococci other than S. lugdunensis other than S. lugdunensis (catheter removed) (catheter removed) CRBSI with persistent bacteremia CRBSI with persistent bacteremia and fungemia > 72H following and fungemia > 72H following catheter removal, associated catheter removal, associated endocarditis, or supportive endocarditis, or supportive thrombophlebitis thrombophlebitis CRBSI with associated CRBSI with associated osteomyelitis osteomyelitis Catheter-associated exit site or Catheter-associated exit site or tunnel infection without tunnel infection without associated bacteremia or associated bacteremia or fungemia fungemia

RECOMMENDED DURATION OF THERAPY RECOMMENDED DURATION OF THERAPY

STRENGTH OF STRENGTH OF RECOMMENDATION RECOMMENDATION

Minimum of 5 days Minimum of 5 days

B-I/II B-I/II

7 days 7 days

Strong Strong recommendation recommendation moderate-quality moderate-quality evidence for VAP evidence for VAP and very-low and very-low quality for HAP quality for HAP evidence evidence

- Should be afebrile for 48–72 H - Should be afebrile for 48–72 H AND have ≤ 1 associated sign of AND have ≤ 1 associated sign of clinical instability before clinical instability before discontinuation of therapy discontinuation of therapy - 7 days is recommended rather - 7 days is recommended rather than a longer duration. There than a longer duration. There exists situations in which a exists situations in which a shorter or longer duration may be shorter or longer duration may be indicated depending upon indicated depending upon improvement of clinical, improvement of clinical, radiologic, and laboratory radiologic, and laboratory parameters. parameters.

Continue antibiotic therapy until Continue antibiotic therapy until there is evidence that the infection there is evidence that the infection has resolved but not necessarily has resolved but not necessarily until a wound has healed until a wound has healed 1-2 weeks (though some require an 1-2 weeks (though some require an additional 1-2 weeks) additional 1-2 weeks) 2-4 weeks 2-4 weeks

A-II A-II

4-6 weeks 4-6 weeks

B-II B-II

5-7 days OR observation alone (if 5-7 days OR observation alone (if no intravascular or orthopedic no intravascular or orthopedic hardware is present and additional hardware is present and additional blood cultures are obtained after blood cultures are obtained after catheter withdrawal to confirm the catheter withdrawal to confirm the absence of bacteremia) absence of bacteremia)

B-III B-III C-III C-III

shorter if entire infected bone shorter if entire infected bone is removed and probably longer is removed and probably longer if bone remains if bone remains

4-6 weeks from first negative blood 4-6 weeks from first negative blood culture following catheter removal culture following catheter removal

6-8 weeks from first negative blood 6-8 weeks from first negative blood culture following catheter removal culture following catheter removal 7-10 days following catheter 7-10 days following catheter removal and incision and drainage removal and incision and drainage (if indicated) (if indicated)

CRBSI= Catheter-related Bloodstream Infections; DFI= Diabetic foot infections; H= hour(s) CRBSI= Catheter-related Bloodstream Infections; DFI= Diabetic foot infections; H= hour(s)

A-II A-II

A-II for A-II for S. aureus; S. aureus; C-III for other C-III for other pathogens pathogens A-II A-II A-II A-II

PAGE 74

â&#x20AC;&#x201A;Antimicrobial Duration of Therapy Antimicrobial Duration of Therapy This guidance is adopted from the National Antimicrobial Stewardship Taskforce References: 1. Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 international clinical practice guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010;50:625-63. 2. Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40:643-54. 3. Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52(5):e103-e120. 4. Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis 2010;50:133-64. 5. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44(Suppl 2): S27-S72. 6. Kalil AC, Metersky ML, Klompas M. et al. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;63:1-51. 7. Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2004;39:885910. 8. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009;49:1-45. 9. Jenkins TC, Knepper BC, Sabel AL, et al. Decreased Antibiotic Utilization After Implementation of a Guideline for Inpatient Cellulitis and Cutaneous Abscess. Arch Intern Med. 2011;171(12):1072-79. 10. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol 2010;31(5):431-55. 11. Liu C, Bayer A, Cosgrove SE, et al. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children. Clin Infect Dis 2011;52:1-38. 12. Stevens DL, Bisno AL, Chambers HF, et al. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-52.

PAGE 75

IV Antibiotic Step-Down Guidelines IV totoPOPO Antibiotic Step-Down Guidelines Candidates for Antimicrobial Step-Down therapy: • • • • •

Patient is able to tolerate PO medication AND has a functioning GI tract The infection is treatable with oral antimicrobial therapy AND the indications and spectrum of activity are identical or similar between alternative drugs No evidence of malabsorption, dysphagia, or gastrointestinal bleed Patient is hemodynamically stable with improving body temperature and WBC High risk patients who MAY NOT be candidates for PO step-down may be identified by: − Pulse >125bpm − RR >30bpm − Systolic BP < 90 mmHg − T < 35oC OR >40oC, altered mental status

Contraindications to Antimicrobial Step-Down therapy: • Serious infections concomitant with chemotherapy induced severe neutropenia • Infections caused by resistant organisms (i.e. MRSA, VRE) unresponsive to >1 course of antimicrobials • Situations where oral antimicrobials may not achieve adequate drug concentrations at the site of infection (i.e. meningitis, endocarditis) • Oral antimicrobial therapy may be used in neutropenic patients with negative blood cultures, temperatures < 38oC, and no indication of clinical sepsis Table 1. IV to PO Antimicrobial Step-Down Options IV Antimicrobial

PO Antimicrobial

Ampicillin/sulbactam

Amoxicillin/clavulanate

Azithromycin

Cefazolin/Ceftazidime

Cephalexin/Cephadrine

Ciprofloxacin

Ciprofloxacin*

Ceftriaxone

Cefpodoxime

Cefuroxime

Cefuroxime axetil

Clindamycin

Clindamycin*

Doxycycline

Fluconazole

Fluconazole*

Moxifloxacin

Moxifloxacin *

Metronidazole

Metronidazole*

Nafcillin

Dicloxacillin

Trimethoprim/sulfamethoxazole

Trimethoprim/sulfamethoxazole*

*Oral drugs which achieve serum levels similar to the parenteral dose form BP= blood pressure; bpm= beats/breaths per minute; GI= Gastrointestinal; IV= intravenous; MRSA= Methicillin-resistant Staphylococcus aureus; PO= by mouth; RR= Respiratory rate; T= temperature; VRE= Vancomycin-resistant enterococci; WBC= White blood cells

PAGE 76

Twelve Twelve Steps to Prevent Antimicrobial Resistance Steps to Prevent Antimicrobial Resistance Twelve Steps to Prevent Antimicrobial Resistance 1. Wash your hands! 1. Vaccinate Wash your hands! 2. 2. Get Vaccinate 3. the catheters and lines out 3. Obtain Get thecultures catheters and lines out 4. 4. Target Obtainthe cultures 5. pathogen 5. Seek Target the pathogen 6. expert input 6. Know Seek expert input 7. the local sensitivity patterns 7. Know the local sensitivity patterns

8. Know when to say “NO” to broad spectrum 8.agents Know when to say “NO” to broad spectrum agentsinfection - not colonization 9. Treat 9. Treat 10. Treatinfection infection- -not notcolonization contamination 10. Stop Treattreatment infection -when not contamination 11. infection is cured 11. or Stop treatment when infection is cured unlikely or unlikely 12. Prevent transmission 12. Prevent transmission

Adopted from the Centers for Disease Control Campaign for Clinicians

Based isolation Precautions Transmission Transmission Based Isolation Precautions Transmission Based isolation Precautions TYPES OF PRECAUTIONS FOR INFECTION CONTROL Precaution Standard Precaution Standard

Gowns

TYPES OF Gloves PRECAUTIONS FORMasks INFECTION CONTROL Hands

If splattering Gowns of body fluids orof If splattering blood is likely body fluids or blood is likely

For contacts Gloveswith mucous For contacts with membranes, mucous non-intact skin membranes, and ALL body non-intact skin fluids and ALL body

If aerosolization Masks or splattering of If aerosolization body fluids or of or splattering blood is likely body fluids or blood is likely

WASH upon Hands entering and WASH upon leaving enteringroom and

Conditions ALL patients Conditions ALL patients

leaving room

fluids Use Transmission Based Precautions below in addition to Standard Use Standard Precautions on all patients. PrecautionsBased Precautions below in addition to Standard Use Standard Precautions on all patients. Use Transmission Precautions CATEGORY SPECIFIC ISOLATION PRECAUTIONS /TRANSMISSION BASED PRECAUTIONS CATEGORY SPECIFIC ISOLATION PRECAUTIONS /TRANSMISSION BASED PRECAUTIONS Approved, fit-

Airborne Airborne

Not necessary

tested Approved, fitrespirator tested protection respirator and required N-95 protection and mask required N-95

WASH upon entering and WASH upon leaving enteringroom and

leaving room

mask

Contact Contact

Upon entering patient room Upon entering patient room

Upon entering room for all Upon and entering contacts room andwith for all patient contactsand with surfaces or patient and equipment surfaces or in room equipment in

For suctioning, if organism is in if For suctioning, sputum organism is in

WASH upon entering and WASH upon leaving enteringroom and

Within three feet of the patient Within three feet (regular masks) of the patient

WASH upon entering and WASH upon leaving enteringroom and

Not necessary

WASH upon entering and WASH upon leaving enteringroom and

sputum

leaving room

room

Droplet Droplet

Not necessary Not necessary

To handle respiratory To handle secretions respiratoryor suctioning secretions or suctioning

Protective Environment Protective Environment

Not necessary

(regular masks)

leaving room

Tuberculosis or rule out tuberculosis. Tuberculosis or rule Respiratory phase of out tuberculosis. measles and chicken Respiratory phase of pox measles and chicken

pox Infected or colonized patients, whether Infected or colonized bedridden or patients, whether ambulatory, bedridden orwith wounds or diarrhea: ambulatory, with multi-resistant wounds or diarrhea: organisms, MRSA, VRE, multi-resistant ESBL, CRE/KPC, or C. organisms, MRSA, VRE, difficile diarrheaor C. ESBL, CRE/KPC,

MRSA sputum, difficileindiarrhea Neisseria meningitidis, MRSA in sputum, drug resistant Neisseria meningitidis, pneumococci, drug resistant diptheria, pertussis, pneumococci, influenza diptheria, pertussis,

influenza Neutropenia (< 1000 neutrophils), <100 Neutropenia ANC (< 1000

Not necessary Not necessary Not necessary neutrophils), ANC <100 Refer to Policy MCM 111-P26 Standard and Transmission Based leavingPrecautions room Call Infection Prevention and Control for further guidance at ext 2654 Refer to Policy MCM 111-P26 Standard and Transmission Based Precautions Call Infection Prevention and Control for further guidance at ext 2654

PAGE 77

Pharmacokinetic Calculations

Pharmacokinetic Calculations Pharmacokinetic Calculations

Ideal Body Weight (IBW) Calculation: Male:Body Weight (IBW) Calculation: 50 kg + [2.3 kg for each inch over 5 feet] Ideal Female: 45 kg + [2.3 kg for each inch over 5 feet] Male: 50 Female: 45using kg + [2.3 kg for each inch over 5 feet] Creatinine Clearance (CrCl) Cockcroft-Gault Equation: Creatinine is expressed in mL/min using Cockcroft-Gault Equation: Creatinine Clearance (CrCl) Creatinine is expressed in mL/min CrCl (mL/min) =(140 – age) (IBW in kg)* ‡ * mg/dL) CrCl (mL/min) =(14072– (SCr age)in (IBW in kg) ‡ 72 (SCr in mg/dL) NOTE: For Females multiply by 0.85

NOTE: For Females multiply by 0.85 CrCl for elderly patients or when no height is available: CrCl for elderly patients=(114 or when no *age)) height is available: CrCl (mL/min) – (0.8 ‡ SCr–in(0.8 mg/dL *age)) CrCl (mL/min) =(114 ‡ SCrmultiply in mg/dLby NOTE: For females 0.9

NOTE: For females multiply by 0.9 patients actual body weight is less than IBW, use actual body weight to calculate actual body weight is less than IBW, use actual body weight to calculate ‡CrCl If patient is underweight/cachectic, may consider rounding SCr up to 1 mg/dL.1,2 *If

*CrCl If patients

‡Do not round to 1 mg/dL for all patients 60 yearsrounding of age.3-5SCr If patient is underweight/cachectic, may >consider

up to 1 mg/dL.1,2 3-5 Do not round to 1 mg/dL for all patients > 60 years of age. Adjusted Body Weight (aminoglycoside dosing) Use adjusted body weight (AdjBW) whendosing) actual body weight (ABW) is ≥ 30% of ideal Adjusted Body Weight (aminoglycoside bodyadjusted weight (IBW) Use body weight (AdjBW) when actual body weight (ABW) is ≥ 30% of ideal AdjBW = 0.4 (ABW - IBW) + IBW body weight (IBW) AdjBW = 0.4 (ABW - IBW) + IBW IBW= Ideal Body Weight (in kg); AdjBW= Adjusted Body Weight; ABW= Actual Body Weight; CrCl= Creatinine clearance; SCr= serum creatinine IBW= Ideal Body Weight (in kg); AdjBW= Adjusted Body Weight; ABW= Actual Body Weight; CrCl= Creatinine clearance; SCr= serum creatinine

References: 1. Robert S, Zarowitz BJ, Peterson EL, Dumler F. Predictability of creatinine clearance estimates in critically ill patients. Crit Care Med. References: 1993;21(10):1487-1495. 1. Robert S, Zarowitz BJ, Peterson EL, Dumler F. Predictability of creatinine clearance estimates in critically ill patients. Crit Care Med. 2. Khuu T, Bagdasarian G, Leung J, et al. Estimating aminoglycoside clearance and creatinine clearance in underweight patients. Am J Health1993;21(10):1487-1495. Sys Pharm. 2010;67(4):274-279. 2. Khuu T, Bagdasarian G, Leung J, et al. Estimating aminoglycoside clearance and creatinine clearance in underweight patients. Am J Health3. Bertino JS. Measured versus estimated creatinine clearance in patients with low serum creatinine values. Ann Pharmacother. Sys Pharm. 2010;67(4):274-279. 1993;27(12):1439-1442. 3. Bertino JS. Measured versus estimated creatinine clearance in patients with low serum creatinine values. Ann Pharmacother. 4. Smythe M, Hoffman J, Kizy K, Dmuchowski C. Estimating creatinine clearance in elderly patients with low serum creatinine concentrations. 1993;27(12):1439-1442. Am J Hosp Pharm. 1994;51(2):198-204. 4. Smythe M, Hoffman J, Kizy K, Dmuchowski C. Estimating creatinine clearance in elderly patients with low serum creatinine concentrations. 5. Dowling TC, Wang E-S, Ferrucci L, Sorkin JD. Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Am J Hosp Pharm. 1994;51(2):198-204. Enrolled in the Baltimore Longitudinal Study on Aging: Impact on Renal Drug Dosing. Pharmacotherapy. 2013;33(9):912-921. 5. Dowling TC, Wang E-S, Ferrucci L, Sorkin JD. Glomerular Filtration Rate Equations Overestimate Creatinine Clearance in Older Individuals Enrolled in the Baltimore Longitudinal Study on Aging: Impact on Renal Drug Dosing. Pharmacotherapy. 2013;33(9):912-921.

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