MKSAP® 17
Medical Knowledge Self-Assessment Program®
Infectious Disease
Infectious Disease
Infectious Disease
150591010 150591010
19 AMA PRA Category 1 Credits™ available until December 31, 2018.
Table of Contents Central Nervous System Infections Meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Viral Meningitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bacterial Meningitis . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Focal Central Nervous System Infections. . . . . . . . . . . . . . 4 Brain Abscess. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Spinal Epidural Abscess . . . . . . . . . . . . . . . . . . . . . . . . 5 Cranial Subdural Empyema. . . . . . . . . . . . . . . . . . . . 6 Encephalitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Herpes Simplex Encephalitis. . . . . . . . . . . . . . . . . . . . 7 Varicella-Zoster Virus Encephalitis. . . . . . . . . . . . . . . 7 Neuroinvasive West Nile Virus. . . . . . . . . . . . . . . . . . . 8 Autoimmune Encephalitis. . . . . . . . . . . . . . . . . . . . . . 8
Urinary Tract Infections Epidemiology and Microbiology. . . . . . . . . . . . . . . . . . . . 26 Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Asymptomatic Bacteriuria. . . . . . . . . . . . . . . . . . . . . 27 Cystitis in Women. . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Acute Pyelonephritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Recurrent Urinary Tract Infections in Women . . . . 28 Acute Bacterial Prostatitis. . . . . . . . . . . . . . . . . . . . . . 28
Mycobacterium tuberculosis Infection
Prion Diseases of the Central Nervous System Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Creutzfeldt-Jakob Disease. . . . . . . . . . . . . . . . . . . . . . . . . . 9 Variant Creutzfeldt-Jakob Disease. . . . . . . . . . . . . . . . . . . 9
Skin and Soft Tissue Infections Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Community-Associated Methicillin-Resistant Staphylococcus aureus . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Necrotizing Fasciitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Toxic Shock Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Animal Bites. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Human Bites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Diabetic Foot Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Community-Acquired Pneumonia Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Microbiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Site of Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Antimicrobial Therapy. . . . . . . . . . . . . . . . . . . . . . . . Complications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Follow-up. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Babesiosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 Ehrlichiosis and Anaplasmosis . . . . . . . . . . . . . . . . . . . . . 24 Rocky Mountain Spotted Fever . . . . . . . . . . . . . . . . . . . . . 25
14 14 16 17 17 18 19 19
Tick-Borne Diseases Lyme Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Southern Tick–Associated Rash Illness. . . . . . . . . . . . . . . 23
Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Clinical Manifestations. . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 Diagnostic Testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Tuberculin Skin Test. . . . . . . . . . . . . . . . . . . . . . . . . 30 Interferon-Îł Release Assays . . . . . . . . . . . . . . . . . . . . 31 Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Culture and Additional Microbiologic Testing. . . . . 31 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis . . . . . . . . . . . . . . . . . . . 35 Prevention. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Nontuberculous Mycobacterial Infections Mycobacterium avium Complex Infection. . . . . . . . . . . 37 Mycobacterium kansasii. . . . . . . . . . . . . . . . . . . . . . . . . . 37 Rapidly Growing Mycobacteria. . . . . . . . . . . . . . . . . . . . . 37
Fungal Infections Systemic Candidiasis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Clinical Manifestations and Diagnosis . . . . . . . . . . . 37 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 Aspergillosis and Aspergilloma. . . . . . . . . . . . . . . . . . . . . 38 Mucormycosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 Cryptococcosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Blastomycosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Histoplasmosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 Coccidioidomycosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
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Sporotrichosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 Exserohilum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Botulism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 Tularemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 Viral Hemorrhagic Fever. . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Sexually Transmitted Infections Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Chlamydia trachomatis Infection . . . . . . . . . . . . . . . . . . 43 Neisseria gonorrhoeae Infection. . . . . . . . . . . . . . . . . . . . 43 Specific Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Cervicitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Pelvic Inflammatory Disease. . . . . . . . . . . . . . . . . . 44 Urethritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Epididymitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Anorectal Infections. . . . . . . . . . . . . . . . . . . . . . . . . . 45 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Genital Ulcers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Herpes Simplex Virus. . . . . . . . . . . . . . . . . . . . . . . . . 45 Syphilis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Chancroid. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Lymphogranuloma Venereum. . . . . . . . . . . . . . . . . 49 Genital Warts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
Travel Medicine
Osteomyelitis
Infectious Gastrointestinal Syndromes
Pathophysiology and Classification. . . . . . . . . . . . . . . . . 49 Clinical Manifestations. . . . . . . . . . . . . . . . . . . . . . . . . . . 50 Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 Imaging Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 Laboratory Studies . . . . . . . . . . . . . . . . . . . . . . . . . . 50 Bone Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 Evaluation and Management of Diabetes Mellitus–Associated Osteomyelitis . . . . . . . . . . . . . . . . . . 51 Evaluation and Management of Vertebral Osteomyelitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Campylobacter Infection. . . . . . . . . . . . . . . . . . . . . . . . . 66 Shigella Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Salmonella Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Escherichia coli Infection. . . . . . . . . . . . . . . . . . . . . . . . . . 67 Yersinia Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 Vibrio Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 Clostridium difficile Infection. . . . . . . . . . . . . . . . . . . . . 68 Viral Gastroenteritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 Parasitic Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 Giardia Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Cryptosporidium Infection . . . . . . . . . . . . . . . . . . . . 71 Amebiasis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Cyclospora Infection . . . . . . . . . . . . . . . . . . . . . . . . . 71
Fever of Unknown Origin Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 Causes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Primary Immunodeficiencies Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 Selective IgA Deficiency. . . . . . . . . . . . . . . . . . . . . . . . . . . 54 Common Variable Immunodeficiency. . . . . . . . . . . . . . . 54 Abnormalities in the Complement System. . . . . . . . . . . . 54
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 Malaria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 Typhoid Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 Travelers’ Diarrhea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 Dengue Fever. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 Hepatitis Virus Infection . . . . . . . . . . . . . . . . . . . . . . . . . . 62 Rickettsial Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Brucellosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Travel-Associated Fungal Diseases . . . . . . . . . . . . . . . . . 63 Other Important Diseases . . . . . . . . . . . . . . . . . . . . . . . . 64 Yellow Fever. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 Rabies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 Leptospirosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 Q Fever. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 Ebola. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
Infections in Transplant Recipients Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 72 Antirejection Drugs in Transplant Recipients. . . . . . . . . 72 Posttransplantation Infections. . . . . . . . . . . . . . . . . . . . . . 73 Timeline and Type of Transplant. . . . . . . . . . . . . . . . 73 Specific Posttransplantation Infections . . . . . . . . . . 73 Prevention of Infections in Transplant Recipients . . . . . 75
Health Care–Associated Infections Bioterrorism Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 Anthrax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 Smallpox (Variola). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 Plague. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 Prevention. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 Catheter-Associated Urinary Tract Infections. . . . . . . . . 77 General Information. . . . . . . . . . . . . . . . . . . . . . . . . . 77 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 ix
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Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Surgical Site Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . 78 General Information. . . . . . . . . . . . . . . . . . . . . . . . . . 78 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Central Line–Associated Bloodstream Infections . . . . . 80 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81 Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 Staphylococcus aureus Bacteremia . . . . . . . . . . . . . . . . . 82 Hospital-Acquired Pneumonia and VentilatorAssociated Pneumonia. . . . . . . . . . . . . . . . . . . . . . . . . . . . 82 General Information. . . . . . . . . . . . . . . . . . . . . . . . . . 82 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 Hospital-Acquired Infections Caused by Antimicrobial-Resistant Organisms. . . . . . . . . . . . . . . . 84
HIV/AIDS Epidemiology and Prevention. . . . . . . . . . . . . . . . . . . . . 84 Pathophysiology and Natural History. . . . . . . . . . . . . . . 84 Acute HIV Infection . . . . . . . . . . . . . . . . . . . . . . . . . . 85 Chronic HIV Infection and AIDS. . . . . . . . . . . . . . . . 85 Screening and Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . 85 Initiation of Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 Initial Evaluation and Laboratory Testing. . . . . . . . 86 Immunizations and Prophylaxis for Opportunistic Infections . . . . . . . . . . . . . . . . . . . . . . 87 Complications of HIV Infection in the Antiretroviral Therapy Era. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 Metabolic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . 88 Cardiovascular Disease. . . . . . . . . . . . . . . . . . . . . . . 89 Immune Reconstitution Inflammatory Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Opportunistic Infections . . . . . . . . . . . . . . . . . . . . . 89 Management of HIV Infection. . . . . . . . . . . . . . . . . . . . . 90 When to Initiate Treatment. . . . . . . . . . . . . . . . . . . 90 Antiretroviral Regimens. . . . . . . . . . . . . . . . . . . . . . . 91 Resistance Testing. . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Management of Pregnant Patients with HIV Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 Postexposure Prophylaxis and Preexposure Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
Viral Infections Influenza Viruses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 Clinical Features and Evaluation. . . . . . . . . . . . . . . 93 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 Novel Coronaviruses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 Human Herpesvirus Infections. . . . . . . . . . . . . . . . . . . . 94 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94 Herpes Simplex Viruses. . . . . . . . . . . . . . . . . . . . . . 94 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95 Varicella-Zoster Virus. . . . . . . . . . . . . . . . . . . . . . . . 96 Epstein-Barr Virus. . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 Human Cytomegalovirus. . . . . . . . . . . . . . . . . . . . . . 97
New Topics in Anti-infective Therapy Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 Newer Antibacterial Drugs. . . . . . . . . . . . . . . . . . . . . . . . 98 Lipopeptides and Glycolipopeptides. . . . . . . . . . . . 98 Oxazolidinones. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 β-Lactam Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . 98 Glycylcyclines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 Newer Uses for Older Antimicrobial Agents . . . . . . . . . 98 Trimethoprim-Sulfamethoxazole. . . . . . . . . . . . . . 98 Polymyxins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 Fosfomycin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 Aminoglycosides. . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 Rifamycins. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 Antimicrobial Stewardship . . . . . . . . . . . . . . . . . . . . . . . 100 Outpatient Parenteral Antimicrobial Therapy. . . . . . . . 101
Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 Self-Assessment Test. . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187
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Infectious Disease Central Nervous System Infections Meningitis Viral Meningitis Causes Viral meningitis is the most common cause of “aseptic” meningitis, in which cerebrospinal fluid (CSF) bacterial cultures are negative. Most patients have typical meningitis symptoms, such as fever, nuchal rigidity, headache, and photophobia. A substantial proportion of viral meningitis is caused by enteroviruses, which commonly occur in the summer and fall in temperate climates when these organisms circulate in the environment. Enteroviral meningitis can also occur in winter and spring months; seasonal enteroviral infections are typically caused by coxsackievirus, echovirus, or other nonpolio enteroviruses. Herpes simplex virus (HSV) can also cause meningitis. These meningitis syndromes can be related to primary infections, with central nervous system (CNS) involvement as a secondary consequence, or reactivation of latent infection presenting as aseptic meningitis. Most patients with HSV meningitis associated with primary infection will have genital lesions. HSV type 2 (HSV-2) is more commonly associated with meningitis, whereas HSV type 1 (HSV-1) is associated with encephalitis. An association exists between Mollaret meningitis, a benign recurring form of lymphocytic meningitis, and HSV-2; at least 84% of patients have evidence of HSV-2 in CSF. Primary HIV infection can present with an aseptic meningitis syndrome, which may occur in isolation from the other symptoms. Meningitis due to acute HIV infection is typically self-limited and may be clinically indistinguishable from other viral meningitis syndromes. Mumps virus can cause meningitis, with typical symptoms of fever, headache, and neck stiffness. Since the advent of universal childhood vaccination for measles, mumps, and rubella, the incidence of mumps-related meningitis has dramatically decreased. Meningitis from mumps virus can occur at any point during the course of clinical mumps infection. Parotitis or orchitis may be present. Infections with arboviruses, such as West Nile virus or St. Louis encephalitis virus, can cause meningitis, although these infections more typically produce encephalitis. Cytomegalovirus, Epstein-Barr virus, adenovirus, and varicella virus infections can also cause meningitis.
Diagnosis Symptoms of viral meningitis include fever, headache, neck stiffness, photophobia, and change in mental status and may be indistinguishable from symptoms of bacterial meningitis. Characteristics of the CSF profile are outlined in Table 1. Additional physical examination findings (rash and pharyngitis in acute HIV infection; parotitis or orchitis in mumps-related meningitis) can support the presumptive diagnosis. Polymerase chain reaction (PCR) and other molecular tests are available for diagnosis of numerous viral causes. CSF PCR studies may be used for diagnosing HSV and enterovirus meningitis; antibody detection in CSF is preferred for West Nile virus meningitis. Viral cultures of CSF are not clinically useful because of poor sensitivity and long turn-around times. Serologic testing may be an adjunctive diagnostic tool in meningitis caused by mumps.
Table 1. Typical CSF Findings in Patients with Viral and Bacterial Meningitis CSF Parameter
Viral Meningitisa
Bacterial Meningitis
Opening pressure
≤250 mm H2O
200-500b mm H2O
Leukocyte count
50-1000/µL (50-1000 × 106/L)
1000-5000/µL (1000-5000 × 106/L)c
Leukocyte predominance
Lymphocytesd
Neutrophils
Glucose
>45 mg/dL (2.5 mmol/L)
<40 mg/dL (2.2 mmol/L)e
Protein
<200 mg/dL (2000 mg/L)
100-500 mg/dL (1000-5000 mg/L)
Gram stain
Negative
Positive in 60%-90%f,g
Culture
Negative
Positive in 70%-85%g
CSF = cerebrospinal fluid. aPrimarily
nonpolio enteroviruses (echoviruses and coxsackieviruses).
bValues
exceeding 600 mm H2O suggest the presence of cerebral edema, intracranial suppurative foci, or communicating hydrocephalus.
cRange
may be <100/µL (100 × 106/L) to >10,000/µL (10,000 × 106/L).
dMay
have neutrophil predominance early in infection, but lymphocyte predominance occurs after the first 6 to 48 hours. eThe
CSF-to-plasma glucose ratio is ≤0.40 in most patients.
fThe
likelihood of a positive Gram stain correlates with number of bacteria in the
CSF.
gThe
yield of positive results is significantly reduced by previous administration of antimicrobial therapy.
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Central Nervous System Infections
CONT.
Meningitis can also result from medications; autoimmune diseases; malignancy; and other nonviral infectious causes, including spirochetes, fungi, or mycobacteria. Serology may be helpful to diagnose aseptic meningitis caused by syphilis, Borrelia burgdorferi (Lyme disease), or certain fungal organisms.
Treatment Anti-infective treatments are not available for viral meningitis with the exception of underlying herpes viruses. The primary focus of management in viral meningitis is to distinguish it from other causes of infectious meningitis, particularly bacterial meningitis. Symptomatic and supportive management for viral meningitis and rigorous evaluation to exclude bacterial meningitis are the cornerstones of management. Empiric antimicrobial agents may be initiated until full CSF profiles and cultures are finalized and bacterial meningitis can be excluded. Antibiotics can be started and continued as empiric treatment for 48 to 72 hours, after which most routine CSF cultures will show preliminary results. The increasing availability of enteroviral PCR testing can shorten the time required to exclude bacterial infection. Repeat lumbar puncture can be performed after the initial 2 to 3 days if lack of clinical response is a concern or if documenting the evolution of the CSF profile to that more characteristic of viral meningitis is desired.
Neisseria meningitidis) or travel to regions of the world where certain organisms are more prevalent and endemic (such as sub-Saharan Africa, where endemic meningococcal disease is present) will also increase the risk for bacterial meningitis. The two most common organisms causing bacterial meningitis are Streptococcus pneumoniae and N. meningitidis, which together are responsible for more than 80% of infections (Table 2).
Diagnosis Bacterial meningitis is classically described as producing fever, nuchal rigidity, and altered mental status. However, all three symptoms may not be present in many patients with confirmed disease. Other clinical manifestations that suggest bacterial meningitis include photophobia, headache (often a very severe headache distinctly different from what the patient may typically experience), and dermatologic manifestations (rash, petechiae, purpura) or neurologic abnormalities
Table 2. Causes of Bacterial Meningitis Infecting Organism
Cases (%)
Comments
Streptococcus pneumoniae
>70
Many cases caused by serotypes not covered by pneumococcal vaccination; functionally and anatomically asplenic patients at greater risk
Neisseria meningitidis
12
Can be transmitted through droplet exposure; functionally and anatomically asplenic patients at greater risk
Group B streptococci
7
Persons with diabetes, alcoholism, malignancy, liver disease at risk
Staphylococcus aureus
<5
Primary infection is associated with neurosurgery or CNS prosthetic device; secondary infection arises from bacteremia
Haemophilus influenzae
6
Decreased prevalence in the pediatric age group since type B conjugate vaccine; functionally and anatomically asplenic patients at greater risk
Listeria monocytogenes
<5
Immunosuppressed and decreased cell-mediated immunity (because of medications or medical conditions) as well as age (very old and very young) are risk factors
Gram-negative bacteria
<5
Nosocomial settings; complication of neurosurgery
Key Points
• Viral meningitis is most commonly caused by enteroviruses, herpes simplex virus type 2, and arboviruses. • Clinical signs and symptoms aiding in the diagnosis of viral meningitis include parotitis or orchitis with mumps virus, rash in enterovirus and HIV, pharyngitis with acute HIV, and genital lesions with herpes simplex virus.
HVC
• Viral meningitis is managed supportively, with empiric antimicrobials given only until cerebrospinal fluid cultures exclude bacterial meningitis.
Bacterial Meningitis Causes Bacterial meningitis usually results from bacteremic dissemination of meningeal pathogens that colonize the nasopharynx or from another distant focus of infection but may also occur from contiguous spread of infection to the CSF (sinusitis or otitis media), direct inoculation (traumatic injury or neurosurgical procedure), or prosthetic device infection (CSF shunts or drains, intracranial pressure monitors). Individual host factors, such as colonization of the nasopharynx with potential meningeal pathogens, complement deficiency, anatomic or functional asplenia, glucocorticoid use, diabetes, hypogammaglobulinemia, and altered cellmediated immunity, can also contribute to increased susceptibility to acute bacterial meningitis. Exposure to other persons with bacterial meningitis (for certain pathogens, such as
CNS = central nervous system.
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Central Nervous System Infections
CONT.
(focal neurologic or cranial nerve deficits, seizures). Physical examination maneuvers, such as testing for Brudzinski and Kernig signs, lack adequate sensitivity and specificity, although the presence of one or both of these findings is consistent with bacterial meningitis. Before proceeding with lumbar puncture, it should be determined whether CT of the head should be performed. CT of the head before lumbar puncture is indicated if signs or symptoms of increased intracranial pressure or a CNS mass lesion, such as papilledema, focal neurologic deficits, or altered mental status, are present; it is also indicated in patients who are immunocompromised or have a history of CNS disease (mass lesion, stroke, focal infection). In the absence of these findings, lumbar puncture can be undertaken without CNS imaging. Elevated CSF opening pressure is common. Characteristic CSF profiles in bacterial meningitis are outlined in Table 1. CSF Gram stain and cultures, when obtained before
antimicrobial therapy initiation, are usually diagnostic for the infecting organism. Rapid CSF tests, such as latex agglutination and molecular testing with PCR, can be supplemental diagnostic tools, although the diagnostic utility of latex agglutination testing is limited by a lack of specificity. Elevated CSF lactate levels suggest bacterial meningitis, but this is not a specific finding. Blood cultures, if obtained before antimicrobial therapy, are often positive and may be an adjunctive diagnostic tool in isolating the bacterial causative pathogen if CSF cannot be obtained before antibiotic administration.
Management Suspected bacterial meningitis demands prompt therapy; because of the risk for substantial morbidity and mortality with delayed treatment, empiric therapy is often initiated before CSF results are available (Figure 1). When a presumptive diagnosis of bacterial meningitis has been made, empiric
F i g u r e 1 . Management algorithm for adults suspected of having bacterial meningitis. CNS = central nervous system; c/w = consistent with; CSF = cerebrospinal fluid. Adapted with permission from Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004 Nov 1;39(9):1270. [PMID: 15494903] Copyright 2004 Oxford University Press.
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This self-assessment test contains one-best-answer multiple-choice questions. Please read these directions carefully before answering the questions. Answers, critiques, and bibliographies immediately follow these multiple-choice questions. The American College of Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Self-Assessment Test
Infectious Disease Self-Assessment Test
The American College of Physicians designates MKSAP 17 Infectious Disease for a maximum of 19 AMA PRA Category 1 CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Earn “Instantaneous” CME Credits Online Print subscribers can enter their answers online to earn CME credits instantaneously. You can submit your answers using online answer sheets that are provided at mksap.acponline.org, where a record of your MKSAP 17 credits will be available. To earn CME credits, you need to answer all of the questions in a test and earn a score of at least 50% correct (number of correct answers divided by the total number of questions). Take any of the following approaches: ➢ Use the printed answer sheet at the back of this book to record your answers. Go to mksap.acponline.org, access the appropriate online answer sheet, transcribe your answers, and submit your test for instantaneous CME credits. There is no additional fee for this service. ➢ Go to mksap.acponline.org, access the appropriate online answer sheet, directly enter your answers, and submit your test for instantaneous CME credits. There is no additional fee for this service. ➢ Pay a $15 processing fee per answer sheet and submit the printed answer sheet at the back of this book by mail or fax, as instructed on the answer sheet. Make sure you calculate your score and fax the answer sheet to 215-351-2799 or mail the answer sheet to Member and Customer Service, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106-1572, using the courtesy envelope provided in your MKSAP 17 slipcase. You will need your 10-digit order number and 8-digit ACP ID number, which are printed on your packing slip. Please allow 4 to 6 weeks for your score report to be emailed back to you. Be sure to include your email address for a response. If you do not have a 10-digit order number and 8-digit ACP ID number or if you need help creating a username and password to access the MKSAP 17 online answer sheets, go to mksap.acponline.org or email custserv@acponline.org. CME credit is available from the publication date of December 31, 2015, until December 31, 2018. You may submit your answer sheets at any time during this period.
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Each of the numbered items is followed by lettered answers. Select the ONE lettered answer that is BEST in each case.
Item 1 A 33-year-old woman is evaluated in the emergency department for a 2-month history of fever, lethargy, weight loss, and headache. She moved to the United States from India 4 years ago. Her father died of tuberculosis 20 years ago. Medical history is otherwise unremarkable, and she takes no medications. On physical examination, temperature is 38.6 °C (101.5 °F), blood pressure is 114/70 mm Hg, pulse rate is 94/min, and respiration rate is 18/min. BMI is 20. Except for lethargy, neurologic examination is unremarkable. No abnormalities are noted on ophthalmologic, cardiac, or pulmonary examinations or in the remainder of the physical examination. Cerebrospinal fluid (CSF) studies: Leukocyte count 275/µL (275 × 106), with 98% lymphocytes Glucose 30 mg/dL (1.7 mmol/L) Protein 250 mg/dL (2500 mg/L) CSF opening pressure 150 mm H2O The remainder of a complete blood count and comprehensive metabolic panel are normal. Acid-fast bacilli smear of CSF is negative, but polymerase chain reaction is positive for Mycobacterium tuberculosis. Minimal basilar meningeal enhancement is seen on CT scan of the head without any evidence of cisternal or ventricular abnormalities, midline shift, or mass lesion. In addition to four-drug antituberculous therapy, which of the following is the most appropriate additional treatment? (A) Acetazolamide (B) Dexamethasone (C) Furosemide (D) Ventriculoperitoneal shunt
Item 2 A 33-year-old man is admitted to the hospital after experiencing a generalized tonic-clonic seizure. He has also had increasing weakness of the left hand and arm, headaches, and fever of 1 week’s duration. Medical history is significant for AIDS, without opportunistic infections in the past several years. His last clinic visit was more than 2 years ago, and his family reports that he has been taking his antiretroviral therapy (ART) only intermittently since around that time. On physical examination, temperature is 37.3 °C (99.1 °C), blood pressure is 142/92 mm Hg, pulse rate is 96/min, and respiration rate is 14/min. He is somnolent and slightly confused. His general medical examination is normal. On neurologic examination, there is no nuchal rigidity. Left upper extremity weakness is noted, but the examination is otherwise unremarkable.
Laboratory studies: CD4 cell count Leukocyte count
66/µL 4400/µL (4.4 × 109/L) (differential: 80% polymorphonuclear cells, 12% lymphocytes, 5% eosinophils, 3% monocytes) Negative
Self-Assessment Test
Directions
Cryptococcal antigen, serum Toxoplasma gondii IgG positive, IgM negative
Noncontrast head CT shows a single lesion in the right parietal area. Brain MRI with contrast confirms this lesion with additional smaller lesions in the left frontal, basal ganglia, and cerebellar areas; all show a small surrounding area of enhancement without edema. No meningeal enhancement is seen. Which of the following is the most likely diagnosis? (A) Central nervous system lymphoma (B) Cryptococcosis (C) Progressive multifocal leukoencephalopathy (D) Toxoplasmosis
Item 3 A 59-year-old man is evaluated in the ICU for fever and leukocytosis. He was admitted to the ICU 13 days ago with respiratory failure resulting from Guillain-Barré syndrome and was intubated and mechanically ventilated. On hospital day 9, he developed fever without an increase in secretions or change in oxygenation. A new left lower-lobe infiltrate was seen on chest radiograph, and his leukocyte count was 17,500/µL (17.5 × 109/L). Sputum culture grew methicillin-sensitive Staphylococcus aureus. Nafcillin was started, with temporary resolution of the fever within 48 hours. Medical history is otherwise unremarkable. Medications are nafcillin and intravenous immune globulin. On physical examination, temperature is 38.2 °C (100.8 °F), blood pressure is 132/84 mm Hg, pulse rate is 94/ min, and respiration rate is 18/min. Pulmonary examination reveals decreased breath sounds in the left lower lung field. The remainder of the examination is noncontributory. Laboratory studies show a leukocyte count of 17,300/µL (17.3 × 109/L). Sputum Gram stain reveals 1+ leukocytes and 1+ gram-positive cocci in clusters. A new moderate left pleural effusion, but no increase in the left lower lobe infiltrate, is seen on chest radiograph. CT scan shows left lower lobe consolidation with air bronchograms and a moderate left pleural effusion. Which of the following is the most appropriate next step in management? (A) (B) (C) (D)
Add gram-negative antimicrobial coverage Change nafcillin to vancomycin Perform bronchoscopy with bronchoalveolar lavage Perform thoracentesis
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Self-Assessment Test
Self-Assessment Test
CONT.
100/min, and respiration rate is 18/min. Bibasilar crackles are heard on pulmonary examination, and cardiac examination is significant for an S3. Bilateral lower-extremity edema to the mid-calf is noted. The urinary catheter is draining clear urine. Laboratory study results show a serum creatinine level of 2.8 mg/dL (248 µmol/L) (baseline, 2.2 mg/dL [194 µmol/L]).
Rash of the palm is shown.
Which of the following is the most appropriate management of this patient’s urinary catheter? (A) (B) (C) (D)
Change catheter after 3 days Change catheter now Remove catheter now Remove catheter when kidney function returns to baseline
Item 29 A 57-year-old woman is evaluated for blood cultures growing yeast during long-term intravenous antibiotic therapy. She has completed 4 weeks of a planned 6-week course of intravenous antibiotics for methicillin-sensitive Staphylococcus aureus infective endocarditis. A peripherally inserted central venous catheter (PICC) was placed at the beginning of her treatment. She developed a high fever 3 days ago, and blood cultures drawn peripherally and through the catheter at that time grew Candida species; further identification is pending. Medical history is otherwise negative, and her only medication is nafcillin. On physical examination, temperature is 37.8 °C (100.0 °F), blood pressure is 126/80 mm Hg, pulse rate is 82/min, and respiration rate is 16/min. The eye grounds are clear. Chest examination is unremarkable. Cardiac auscultation reveals a grade 2/6 crescendo-decrescendo murmur at the right upper sternal border. She has no spinal tenderness. The right brachial PICC site is without erythema, drainage, or tenderness. In addition to continuing intravenous antibiotic therapy, which of the following is the most appropriate management? (A) (B) (C) (D)
Continue PICC use Continue PICC use and add antifungal therapy Remove PICC Remove PICC and add antifungal therapy
Item 30 A 23-year-old man is evaluated in the emergency department for a 5-day history of malaise and an erythematous macular and papular rash that began on the chest and spread to involve the extremities. The rash is not pruritic. The patient is sexually active with men; he has a new sexual partner and does not use condoms. He takes no medications and has no known allergies. On physical examination, temperature is 37.6 °C (99.7 °F), blood pressure is 110/65 mm Hg, pulse rate is 90/min, and respiration rate is 12/min. A generalized rash is noted. Cervical, axillary, and inguinal lymph nodes are freely movable and nontender on palpation. No genital or mucosal lesions are present.
Which of the following is the most appropriate treatment? (A) Azithromycin (B) Benzathine penicillin (C) Ceftriaxone (D) Methylprednisolone
Item 31 A 46-year-old woman is admitted to the hospital with abdominal pain, worsening diarrhea, and intermittent low-grade fever of 1 week’s duration. She reports no nausea, vomiting, or swallowing symptoms; no melena or hematochezia; and no rash. She underwent kidney transplantation 4 months ago. She is cytomegalovirus seropositive and received an organ from a cytomegalovirus-seronegative donor; she received valganciclovir for 3 months after transplantation with no clinical or laboratory evidence of cytomegalovirus disease. Medical history is significant for autosomal-dominant polycystic kidney disease. Medications are tacrolimus, prednisone, mycophenolate mofetil, and trimethoprim-sulfamethoxazole. On physical examination, temperature is 37.3 °C (99.1 °F), blood pressure is 144/90 mm Hg, pulse rate is 104/min, and respiration rate is 16/min. BMI is 23. Mucous membranes are dry. The abdomen is soft with mild tenderness in lower quadrants, bowel sounds are normal, and no rebound or guarding is noted. No skin rash is noted, and the remainder of the examination is unremarkable. Stool culture is positive for Candida albicans. Results on Clostridium difficile toxin nucleic acid testing are negative. Plain radiograph of the abdomen is unremarkable and shows a normal bowel gas pattern without free air. Which of the following is the most likely cause for the patient’s diarrhea? (A) Candida albicans (B) Clostridium difficile (C) Cytomegalovirus (D) Mycophenolate toxicity (E) Polyoma BK virus
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Item 1
Answer:
B
Educational Objective: Treat a patient with tuberculous meningitis. This patient has tuberculous meningitis and should receive glucocorticoid therapy in addition to antituberculous therapy. Dexamethasone is recommended for adults with tuberculous meningitis because limited data show some mortality benefits. The recommended dose of dexamethasone is 12 mg/d for 3 weeks, with gradual tapering during the following 3 weeks. Some experts use prednisone instead of dexamethasone, and others recommend a slightly longer duration of glucocorticoid therapy (approximately 8 weeks). The recommendations for duration of treatment of extrapulmonary tuberculosis are generally the same as for pulmonary tuberculosis (6-9 months). However, the recommended treatment duration for tuberculous meningitis is longer (9-12 months), with the exact duration determined by response to therapy and antibiotic sensitivities of the isolate. Diuretics—such as acetazolamide and furosemide, which decrease cerebrospinal fluid (CSF) production by the choroid plexus—have been used as temporizing measures for management of hydrocephalus in patients who are not stable enough to undergo surgical decompression. However, there is no indication for their use in this patient. Patients with tuberculous meningitis can develop hydrocephalus, usually secondary to impaired CSF resorption. Ventriculoperitoneal shunts can be used to manage hydrocephalus. This patient has no evidence of hydrocephalus, which is typically associated with increased intracranial pressures and ventriculomegaly on brain imaging. Serial lumbar punctures after initiation of glucocorticoids and antituberculous medications can be attempted initially in patients with hydrocephalus before attempting surgical drainage with a shunt. Key Point
• Patients with tuberculous meningitis should receive a glucocorticoid in addition to antituberculous therapy.
Bibliography American Thoracic Society; CDC; Infectious Diseases Society of America. Treatment of tuberculosis [erratum in MMWR Recomm Rep. 2005 Jan 7;53(51):1203]. MMWR Recomm Rep. 2003 Jun 20;52(RR-11):1-77. [PMID: 12836625]
Item 2
Answer:
D
Educational Objective: Diagnose central nervous system toxoplasmosis. This patient most likely has central nervous system (CNS) Toxoplasma gondii infection. He has not been adherent to
antiretroviral therapy, and his CD4 cell count has decreased to less than 100/µL, putting him at risk for opportunistic infection. Clinical presentation of CNS toxoplasmosis typically involves new headaches and focal neurologic deficits and may also include fever and seizures. The findings on this patient’s MRI are classic for toxoplasmosis, with multiple ring-enhancing lesions. Because CNS toxoplasmosis in AIDS results from reactivation of earlier infection, patients usually have a positive result for IgG antibody but not IgM. He should be treated empirically and followed for clinical and radiographic response, which typically occurs within 1 to 2 weeks. Primary CNS lymphoma generally requires a more severe degree of immunosuppression than most other AIDS-related complications, most commonly occurring when the CD4 cell count drops below 50/µL; the incidence has decreased with effective antiretroviral therapy. Although primary CNS lymphoma may present with more than one lesion on MRI, it most often presents with a single large lesion. Primary CNS lymphoma is strongly associated with Epstein-Barr virus infection, and polymerase chain reaction of cerebrospinal fluid to detect Epstein-Barr virus can facilitate the diagnosis. The prognosis remains poor. Cryptococcal meningoencephalitis is another common CNS infection in AIDS but rarely results in focal mass lesions on imaging, more often presenting with mental status changes than focal deficits and seizure. The serum cryptococcal antigen and cerebrospinal fluid antigen are positive in 95% and 99% of cases, respectively; therefore, a negative antigen test result argues against this diagnosis. Progressive multifocal leukoencephalopathy presents in AIDS with focal deficits and mental status changes. Onset usually occurs over several weeks, compared with several days for toxoplasmosis, and fever is uncommon. Furthermore, progressive multifocal leukoencephalopathy lesions on MRI are typically white-matter, noninflammatory lesions (unless accompanied by immune reconstitution inflammatory syndrome) with minimal enhancement and no mass effect.
Answers and Critiques
Answers and Critiques
Key Point
• Central nervous system toxoplasmosis in AIDS results from reactivation of earlier infection, typically involves new focal neurologic deficits and headaches, and may also include fever and seizures.
Bibliography Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. http://aidsinfo.nih.gov/contentfiles/lvguidelines/ adult_oi.pdf. Updated April 16, 2015. Accessed July 20, 2015.
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