1. DIAGNOSIS AND MANAGEMENT OF MENINGITIS Created by Stephanie Singson Updated by Saahir Khan

2. Objectives  Learn how to classify meningitis into bacterial, aseptic, or fungal/mycobacterial categories.  Learn diagnostic workup for meningitis  Learn empiric and targeted therapy for meningitis

3. Classify Patient by Presentation  Bacterial Meningitis  Triad of fever, nuchal rigidity, change in mental status  Rapid progression to coma and death  Aseptic Meningitis/Encephalitis  Less febrile, less acute, headache with flu-like symptoms  May have focal neurological symptoms (encephalitis)  Fungal/Mycobacterial Meningitis  Indolent onset, usually immunosuppressed  May have increased ICP (vomiting, double vision) Tunkel et al. IDSA: Bacterial Meningitis. Clinical Infectious Disease. 2004.

4. Classify Patient by Physical Exam  Bacterial Meningitis  Kernig and Brudzinski signs are specific but insensitive  Petechial rash may indicate meningococcemia  Aseptic Meningitis/Encephalitis  May have focal temporal signs (HSV) or paralysis (West-Nile)  Fungal/Mycobacterial Meningitis  Respiratory signs may indicate TB or cocci  Increased ICP (papilledema) may indicate TB or crypto LeBlond, RF et al. DeGowin’s Diagnostic Examination. 10 th Edition. McGraw-Hill Education.

5. Diagnose Patient: Approach Tunkel et al. IDSA: Bacterial Meningitis. Clinical Infectious Disease. 2004.

6. Diagnose Patient: Lumbar Puncture EtiologyNormalBacterialViral/SyphilisFungal/TB AppearanceClearCloudyClearCloudy OP (cm H 2 O)< 20> 2520-25> 25 WBC Count< 5 > 100 (>90% PMN) 10-500 (>50% lymph) 10-500 (>50% lymph) CSF/Serum Glucose> 0.6< 0.4> 0.6< 0.4 Protein (mg/dL)< 45> 50 Further Testing (if indicated) Gram Stain Culture S. pneumo Ag HSV, WNV PCR CMV, VZV PCR Enterovirus PCR VDRL Crypto Ag Cocci, Toxo Ab AFB + Culture Fungal Culture CXR Medscape

7. Treat Patient: Bacterial Meningitis  Initial Therapy  Strep pneumo, Neisseria meningitides, H. influenza Treat with ceftriaxone and vancomycin (better strep coverage)  Listeria monocytogenes (age>50 or immunocompromise) Add ampicillin  MRSA, Pseudomonas (post-neurosurgery or skull trauma) Switch ceftriaxone to cefepime or meropenem  Adjunctive Measures  Add dexamethasone (reduces death by pneumococcus)  Droplet isolation (until meningococcus ruled out)  Target therapy to CSF gram stain and culture

8. Treat Patient: Aseptic Meningoencephalitis  Initial Therapy  HSV in community, VZV if zoster, CMV post-transplant Add acyclovir (HSV, VZV) or ganciclovir (CMV)  Syphilis if STI risk or immunocompromise Add penicillin  Adjunctive Measures  Consider IFN, IVIG for refractory WNV (minimal data) UpToDate

9. Treat Patient: Fungal/TB Meningitis  Targeted Therapy  IV amphotericin B + flucytosine for crypto  Sulfadiazine + pyrimethamine for toxo  Fluconazole for cocci (+ intrathecal ampho if severe)  RIPE for at least 1 year for TB  Adjunctive Measures  Consider serial LP or ventricular drain for elevated ICP  Add dexamethasone for TB (reduces mortality)  Airborne isolation for active TB if respiratory symptoms Galgiani et al. IDSA: Coccidiomycosis. Clinical Infectious Disease. 2005.UpToDate

10. Case Example  Mr. B is a 70-year-old man with history of CAD and HTN brought by family from home to the ED for fever and confusion that started this morning.  On presentation, vitals were T 38.3C (101F), BP 96/52, HR 101/min, RR 20/min. On exam, mental status was drowsy, patient was oriented only to person, and neurological exam was non-focal.

11. How would you manage Mr. B? Droplet isolation. Non-contrast head CT. Indication: Abnormal level of consciousness Result: Negative for bleed or acute abnormality Draw blood cultures. Perform LP. Result: Opening pressure 300 mmH2O Leukocyte count 600/uL (80% neutrophils, 20% lymphocytes) Glucose level 30mg/dL Protein level 350mg/dL Gram stain negative Administer empiric therapy: Dexamethasone, Vancomycin, Ceftriaxone, Ampicillin (age> 50) Await culture results to target antibiotic regimen.

12. Summary  Meningitis can be divided into bacterial, aseptic (viral or syphilis), and fungal/mycobacterial categories  Lumbar puncture is primary tool for diagnosis  Preceded by imaging if risk for CNS pathology  Treatment is initially empiric, then targeted to pathogen  Empiric vancomycin/ceftriaxone/ampicillin/dexamethasone for community-acquired bacterial meningitis and acyclovir for aseptic meningoencephalitis