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August CE Article
August CPE Article
Community-Acquired Pneumonia 2019 Guidelines: Outpatient Therapeutic Updates
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Authors: Taylor Hawkins, PharmD, Julie Harting, PharmD, BCIDP, and Julie Burris, PharmD
The authors declares that there are no financial relationships that could be perceived as real or apparent conflicts of interest.
Universal Activity # 0143-0000-20-008-H01-P &T 1.0 Contact Hour (0.10 CEU) Expires 8/31/23
KPERF offers all CE articles to members online at www.kphanet.org
Learning Objectives: At the conclusion of this Knowledge-based article, the reader should be able to:
1.
Identify community-acquired pneumonia pathogens and limitations in the laboratory
Define literature and guideline updates related to community-acquired pneumonia
Compare differences between the 2007 and 2019 Infectious Diseases Society of America guidelines.
Introduction:
Pneumonia is a lower respiratory tract infection that can lead to severe illness in all ages. Milder cases can be treated in the outpatient setting, however severe cases require hospitalization. The lungs are exposed to gases, particles, and microbes in the air continuously.1 Pneumonia occurs when a large amount of an organism is present in the lower respiratory tract, or when the natural defense mechanisms are overwhelmed.1 Pneumonia typically presents with a fever and respiratory symptoms consisting of cough, sputum production, chest pain, shortness of air and tachypnea. 2 Upon physical examination, the patient may present with crackles or rales.3 These signs and symptoms may also be accompanied with laboratory and vital abnormalities such as leukocytosis (increased white blood cells), tachycardia, low oxygen level, and a difference in procalcitonin level.3 Pneumonia is usually confirmed by visualizing infiltrates on a chest radiographic imaging, which is a crucial part of diagnosis.
Community-acquired pneumonia (CAP) occurs in patients who have not resided in a hospital, long-term care facility, or nursing home 14 days prior to illness onset.1 In comparison, patients who are exposed to the above healthcare settings, or have been hospitalized or mechanically ventilated for > 48 hours are categorized differently as hospital-acquired (HAP) or ventilator-associated pneumonia (VAP).4 In 2017, there were approximately 50,000 deaths due to all types of pneumonia according to the Centers for Disease Control and Prevention (CDC), and pneumonia, along with influenza, is considered the 9th leading cause of death in the United States. 5 After twelve years, the Infectious Disease Society of America (IDSA and American Thoracic Society ATS) issued a CAP guideline update in Fall 2019. In this time gap, the term health care-associated pneumonia (HCAP) was removed due to over-utilization of broad-spectrum antimicrobial therapy in that patient population, antimicrobial resistance for common CAP pathogens changed, and evidence regarding corticosteroid treatments became available. This article will summarize changes to management of outpatient CAP.
Diagnosis and limitations:
The updated guidelines highlight that the majority of patients will not have the etiology of CAP identified. In a multicenter, prospective study titled Etiology of Pneumonia in the Community (EPIC), Jain S, et al evaluated 2,320 hospitalized patients with CAP. Radiographic evidence and diagnostic methods were required to participate in the study. Sixty-two percent of the patients had no pathogen detected. Of those with an identified pathogen, 24% were viral, 11% bacterial, 1% fungal, and 3% co-infection.6 Due to the low yield of pathogen identification, in an outpatient setting, neither blood cultures nor sputum gram stain or culture should be routinely performed. Both types of cultures (blood or respiratory) are only recommended in the setting of severe, inpatient CAP.2
commonly associated No comorbidities or risk factors Comorbidities (heart, lung, liver, renal disease, diabetes, alcowith CAP than previholism, malignancy, and asplenia) ously thought. Single agent therapy options Combination therapy options When influenza is Amoxicillin 1 gram PO TID (preferred) Amoxicillin/clavulanate (500 mg/125 mg PO TID or currently occurring in the community, it is OR Doxycycline 100 mg PO BID OR 875/125 mg PO BID or 2000 mg/125 mg po BID) OR a cephalosporin (cefpodoxime 200 mg PO BID or cefuroxime 500 mg PO BID) recommended to test for influenza A and B. A macrolide (if local resistance <25%) Azithromycin 500 mg PO on day 1 and AND a macrolide or doxycycline Nasal swabs are prethen 250 mg PO daily ferred, and a sputum culture has a lower Clarithromycin 500 mg PO BID or Clarithromycin ER 1000 mg PO daily Single agent therapy option Respiratory fluoroquinolone yield for detection. levofloxacin 750 mg PO daily The CDC notes that rapid influenza testing moxifloxacin 400 mg PO daily has a sensitivity ranging from 50-70%. This means, almost half of the time there is outpatient setting is minimal. a false negative for influenza. Sensitivity to detect influenza B
is lower than for detection of influenza A. For other viral species, since viral culture results and serial antigen testing may The 2019 guidelines recommend the use of the pneumonia not be available until weeks after an acute illness and can inseverity index (PSI) over the CURB-65 score to determine volve invasive techniques for sampling, polymerase chain reneed for hospitalization. The CURB-65 score is simpler and action (PCR) technology has replaced these techniques due to based on five criteria; urea, confusion, respiratory rate, blood increase sensitivity and specificity.7 The rate of detection inpressure, and age ≥ 65 years old. The PSI score is much more creases by 50% compared to other methods. The sensitivity of detailed containing 20 variables including comorbidities, laPCR for the eight most common respiratory viruses ranges boratory values, imaging results, and clinical presentation. from 95-100% with a 99-100% specificity. Mixed viral infecThe PSI scores patients as one of five mortality classes and, is tions are detected in up to 30% of specimens. The assay deconsidered better for predicting mortality, and identifies more tects and differentiates between influenza A and B, respiratory patients as low risk. The PSI score determines overall mortalisyncytial virus (RSV), parainfluenza, human metapneuty risk and breaks the patients into groups. Risk groups II, III, movirus, rhinovirus, coronavirus, and adenovirus. The sample and I are determined to be low risk and can be treated in the is of the nasopharyngeal and the turnaround time is six and a outpatient setting. Risk groups IV and V correlate with moderhalf hours.8 ate and high risk and require hospitalization. However, the The most common bacterial causes of CAP are Streptococcus pneumoniae followed by Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, Legionella species, Chlamydia pneumoniae, and Moraxella catarrhalis.2 As stated above, blood and sputum cultures should only be obtained in hospitalized patients who have severe CAP, are intubated, PSI score is an unrealistic index in the outpatient setting due to the many of the laboratory and radiographic findings needed. Severe CAP classification has not changed since the 2007 IDSA/ATS guidelines, which includes criteria of respiratory rate, confusion, uremia, leukopenia, thrombocytopenia, hypothermia, and hypotension. who are receiving empiric coverage for methicillin-resistant S. The 2019 guidelines also recommend against the use of IV aureus (MRSA) or P. aeruginosa, or who have been hospitalcorticosteroids except in circumstances of septic shock. This ized and/or received IV antibiotics in the past 90 days.2 Other may come as change of practice, but the authors of the guidenon-respiratory diagnostic testing such as pneumococcal urilines cite evidence for their lack of support. Corticosteroids are nary antigen or Legionella urinary antigen should also not be not recommended for outpatient community-acquired pneuperformed in an outpatient setting unless recent travel or semonia. vere CAP. A prospective, multicenter study including 1,941 Treatment for outpatient setting: patients evaluated the sensitivity and specificity of these urine
Clinical updates in new guidelines:2
antigen tests. Of the 64% of patients who received a LegionelDrug-resistant Streptococcus pneumoniae is a nationwide la urinary antigen test, only 1.6% (32 patients) were positive. problem. The CDC 2019 Antibiotic Resistance Threats in the Similarly, of the 61% of patients receiving a pneumococcal United States report mentioned there were twice as many urinary antigen test, only 4.2% (81 patients) were positive.9 deaths from antibiotic resistance than previously reported in a Therefore, the clinical utility of these tests, particularly in the similar 2013 report.10 Overall, rates of drug-resistant pneumo
Streptococcus pneumoniae
Atypical bacteria (Chlamydia sp., Legionella sp, Mycoplasma sp)
Haemophilus influenzae Non-betalactamase producing Betalactamase producing
Staphylococcus aureus MSSA
MRSA
Moraxella catarrhalis
Respiratory Viruses
Respiratory flouroquinolone
✓
Footnote: Amoxicillin. In: Sanford Guide [online database]. Sperryville, VA. Accessed on 2020 Apr 19. Doxycline. In: Sanford Guide [online database]. Sperryville, VA. Accessed on 2020 Apr 19. Erythromycin. In: Sanford Guide [online database]. Sperryville, VA. Accessed on 2020 Apr 19. Levofloxacin. In: Sanford Guide [online database]. Sperryville, VA. Accessed on 2020 Apr 19. Cephalosporins. In: Sanford Guide [online database]. Sperryville, VA. Accessed on 2020 Apr 19.
Amoxicillin-Clavulanate does cover for Moraxella catarrhalis.
coccal infections have decreased from 2005 to 2017 as a result of vaccination. However, macrolide resistant among Streptococcus pneumoniae has increased since the 2013 report.10 Based on several large healthcare institution antibiograms in the greater Louisville area, macrolide resistance in Kentucky is on average 50%. Macrolide monotherapy was previously recommended as first-line outpatient therapy in the 2007 guidelines, but is now only recommended when local resistance is less than 25%. Therefore, the majority of Kentuckians should no longer be prescribed macrolide monotherapy for outpatient CAP. Instead, high-dose amoxicillin is now recommended as the preferred CAP outpatient treatment regimen for patients without comorbidities or risk factors (Table 1). High doses of amoxicillin help combat resistance of Streptococcus pneumoniae. The mechanism of resistance to penicillin is through alteration in the molecular cell wall targets, also called penicillin-binding proteins.11 Mutations that alter the binding proteins result in decreased affinity of agents, causing them to be less effective.11 This resistance can be overcome if the concentration of the agent exceeds a MIC for 40-50% of the dosing interval.11 Therefore, with higher dose of amoxicillin, the resistance is combated. When prescribing amoxicillin for CAP, there is a loss of coverage for other common CAP pathogens. Amoxicillin adds more robust coverage for drug-resistant Streptococcus pneumoniae, but lacks coverage for other common pathogens for CAP (Table 2). Guideline authors supported this switch since Streptococcus pneumoniae is the most prevalent CAP pathogen.
Doxycycline or macrolide monotherapy can be used if there is a contraindication to amoxicillin, including a serious hypersensitivity to penicillin. A serious hypersensitivity includes a reaction of anaphylaxis, Stevens-Johnson syndrome and hives. It is important to clarify penicillin allergies and determine if it was a childhood or adult reaction. While doxycycline resistance has also been increasing worldwide. 12 In the Louisville metro area, Streptococcus pneumoniae is susceptible on average 80% of the time per the antibiograms mentioned above. Therefore, doxycycline has better coverage against Streptococcus pneumoniae compared to a macrolide. Table 2 compares coverage of these two agents for common CAP pathogens. Even though doxycycline has better coverage, it also has a more broad-spectrum therapy. Antimicrobial stewardship strategies promote use of narrow spectrum agents when possible. It would not be appropriate to use doxycycline in a patient with no contraindication for amoxicillin for antimicrobial stewardship purposes. Doxycycline has drug interactions with warfarin, iron or calcium supplements, bile acid sequestrants, carbamazepine, proton pump inhibitors and more agents. Doxycycline can cause photosensitivity, discoloration of teeth (especially in children), and gastrointestinal intolerance.
In outpatients with comorbidities of heart, lung, liver, renal disease, diabetes, alcoholism, malignancy, or asplenia, combination therapy is recommended. Combination therapy should include amoxicillin-clavulanate or an oral cephalosporin with a macrolide or doxycycline. Patients with comorbidities can also be treated with monotherapy using an oral respiratory fluoroquinolone (Table 1). In the Louisville metro area, Streptococcus pneumoniae is susceptible on average 100% of the time per the antibiograms mentioned above. Fluoroquinolones have an increased risk of QTc prolongation, hepatotoxicity, phototoxicity, a black box warning oftendon rupture, increased risk of seizures. Fluoroquinolones have interactions with antidepressants, antiarrhythmics, antipsychotics, warfarin, antacids, calcium, and multivitamins. Risk factors for MRSA and Pseudomonas should also be a factor for determining treatment in the outpatient setting. Risk factors for MRSA include a positive culture in the past year, recurrent skin infections, severe pneumonia, and IV antibiotic use or hospitalization in the past 90 days. Pseudomonas risk factors include a positive culture in the past year, severe COPD, invasive respiratory procedures or support, and IV antibiotic use or hospitalization in the past 90 days. Treatment for patients with risk factors for MRSA should include a combination therapy of a beta lactam and a macrolide (Table 1).2
Oseltamivir is indicated in patients that test positive for influenza in the inpatient and outpatient setting regardless of duration of illness prior to diagnosis. Benefit has been seen up to 4- 5 days after onset of influenza symptoms, however 48 hours after symptom onset shows the most benefit. This recommendation is consistent with the 2009 IDSA Influenza guidelines.13 However, the CDC also lists inhaled zanamivir, intravenous peramivir, and oral baloxavir as viable treatment options. The CDC recommends in the setting of severe or complicated illness defined as pneumonia or a chronic medical condition, oseltamivir should be started as soon as possible if not hospitalized. If no evidence of a bacterial infection, antibacterial therapy should be stopped in 48-72 hours as an antimicrobial stewardship initiative. However, empiric antimicrobial therapy should not be held in a positive influenza setting with pneumonia.
Duration of treatment for CAP should be guided by clinical stability and normal mentation. The duration of therapy should be no less than 5 days. Follow up imaging should not be obtained.
Role of the pharmacist:
Pharmacists can recommend pneumococcal vaccination to protect against Streptococcus pneumoniae, especially for patients who are at high risk of developing pneumonia. The CDC recommends to all patients 65 and older to receive the pneumococcal polysaccharide vaccine (PPSV23). For patients age 19-64 years with medical conditions including heart, lung, or liver disease, alcoholism, or a smoker should receive 1 dose of the PPSV23. Once this group turns 65 years and older, they should receive another dose of PPSV23 5 years after the first dose.
For patients 19 and older with immunocompromising conditions should receive 1 dose of PCV13 followed by 1 dose of PPSV23 8 weeks later, then another dose of PPSV23 5 years later. At the age of 65, should receive PPSV23 5 years after the most recent PPSV23 dose.
The patient should also receive the influenza vaccine yearly as the flu commonly presents with pneumonia. Patients 65 and older should receive a high dose influenza vaccine (Fluzone high dose or Fluad). Smoking cessation can also be discussed with the patient and pharmacists can recommend appropriate nicotine replacement therapies. Counseling from the pharmacist can help with overall compliance of antibiotic therapy from the patient and help with antibiotic stewardship.
Over the counter medications can help some of the symptoms for pneumonia. Fever reducers/ pain relievers included acetaminophen, ibuprofen, naproxen, or aspirin can help. Cough symptoms of pneumonia can also be treated with expectorant cough medicines like Mucinex or Robitussin decongestants.
Conclusion:
Overall, the recommendations for the 2019 guidelines included more information on diagnosis and routine labs. The overall empiric therapy has not been changed much from the 2007 guidelines. However, increased macrolide resistance has made macrolide monotherapy less favored. For outpatient community-acquired pneumonia the following changes have been made: beta lactam therapy preference over macrolide monotherapy and cultures should not be routinely taken. For inpatient or severe CAP, many more changes occurred such as corticosteroid use for patients with sepsis, sputum and blood cultures in severe disease and patients empirically receiving treatment for MRSA or Pseudomonas aeruginosa, and procalcitonin therapy is not recommended to determine etiology.
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