BACTERIAL MENINGITIS IN ADULTS CLINICAL MANAGEMENT COURSE Valentine’s Day 2007 Allen B. Kaiser, M.D.

Case Example History A 59 y.o. male Nashville Union Mission resident presents to the ED with 2 days of high fever and progressive headache. His friend brought him in when he became confused and lethargic. The patient has Type II diabetes and drinks ‘every day’ but no other illness, although his roommate believes he heard the patient talk of having had a seizure during an illness when young.

Case Example Exam On exam he is cooperative and oriented but lethargic. Temp is 102.8, P 110, R 20, BP 110/60. He is complaining of a severe headache. He has a 2+ stiff neck on flexion. No other physical findings of note are present.

Course of Action (T or F) It would be best to obtain head CT before LP. Steroids should be avoided as they have been shown to reduce antibiotic levels in CSF. Antibiotic therapy is indicated if more than 80% PMN are observed in CSF While a CSF glucose of 40 mg/dl is highly suggestive of bacterial meningitis, VERY low glucose (e.g., 15 mg/dl) ALWAYS demands Rx Were patient to go untreated for several hours and were to die, microscopic slides of brain tissue would reveal clusters of microorganisms.

Host Immune Defects Predisposing to Meningitis Host Problem Organism favored Frequency of defect actually leading to infection Absence of opsonizing antibody S. pneumoniae Common in all ages groups H. influenzae Common in very young children Asplenia: surgical or functional Rare N. meningitidis Very Rare Complement deficiency Corticosteroid excess L. monocytogenes C. neoformans HIV infection C. neuformans 5% acquire cryptococcal meningitis Bacterial Endocarditis S. aureus Various gram-negative rods Fracture of cribriform plate S. pneumoniae or other oral flora Very rare

CLASSIC SIGNS AND SYMPTOMS OF ACUTE BACTERIAL MENINGITIS Symptoms: Acute illness manifested by fever, severe headache, stiff neck Often: N&V, CNS impairment Signs: Abnormal CSF characterized by: WBC > 100 per ml CSF glucose <40mg% or <40% blood glucose Predominantly PMN response

PHYSICAL EXAM ON PATIENTS WITH MENINGITIS HEENT: Signs of Meningeal Irritation (90%) [Forget Kernig and Brudzinski signs in adults] Parameningeal foci (50%): sinusitis, otitis, trauma CSF otorrhea, rhinorrhea Papilledema (should not be present) Altered Mental Status (78%) COR-RESP: Signs of Pneumonia (12%), Endocarditis SKIN: Petechiae and/or rashes (meningococcemia) Midline sinuses NEURO: Signs of localized defects

CSF Space: Site of Impaired PMN Leukocyte Function Lack of firm phagocytic surface. Impaired entry of PMN into CSF space. Reduced opsonic activity of CSF. Reduced bactericidal activity of CSF. Low to absent complement in CSF. Low CSF levels of immunoglobulins.

PATHOPHYSIOLOGY OF BACTERIAL MENINGITIS In patients dying from bacterial meningitis, the bacterial pathogens cannot be observed or cultured from neural tissue in the vast majority of patients. Direct ‘invasion’ of brain or spinal cord does not appear to be a part of the pathophysiology of this illness. So…why do patients get confused, have neurological deficits, and die with bacterial meningitis?

Common ‘CSF Myths’ in Patients with Bacterial Meningitis Hypoglycorrachia Primarily due to (a) bacteria eating the glucose; (b) WBCs eating the glucose; (c) both; (d) something else High % of PMN One can assume a bacterial etiology if the % of PMNs is greater than (a) 50%; (b) 80%; (c)100%; (d) something else

CONTROVERSIES IN THE TREATMENT OF BACTERIAL MENINGITIS LP BEFORE CT (CT before LP is associated with 2-hr delay in Dx and 1-hr delay in Rx URGENCY OF THERAPY IMPACT OF RX ON CSF CULTURES STEROIDS

When to begin empiric therapy and obtain head CT before LP? Grossly abnormal mental status -or- Risk of mass lesion (Papilledema, focal neurologic defects, recent head trauma, malignant neoplasm, or h/o CSF mass lesion, -or- Immunosuppressed (transplant, chemotherapy) (In AIDS patients, begin empiric Rx and obtain MRI & ID consult)

EMPIRIC REGIMEN FOR THERAPY OF SUSPECTED BACTERIAL MENINGITIS Dexamethasone 10 mg (q6h x 4d) Ceftriaxone 2 gm (q12h) Vancomycin 1 gm (q12h) For alcoholism or elderly (especially if frail), ampicillin 2 gm (q4h) For cephalosporin allergy (wheezing, anaphylaxis) substitute Meropenem 2 gm (q8h)

Role of Gram’s Stain in Dx and Rx of Bacterial Meningitis* Gram’s stain and culture are positive in over 75% of patients with bacterial meningitis with varying overlap depending on organism and prior use of antibiotics. In one series, Gram’s Stain was positive in 15% of patients with culture negative meningitis Prior antibiotics may increase culture-negative rate by 20% When positive, Gram’s stain will yield Dx on ‘same shift’ * Have you been to the Student Lab or Microbiology Clinical lab?

Predisposing Causes of Pneumococcal (P), Meningococcal (M), and H Predisposing Causes of Pneumococcal (P), Meningococcal (M), and H. influenzae (H) Meningitis Exposure (M, H) - Intimate Family Contact - Day-Care Nurseries -? Grade School Anatomic Defect (P, H) - Basilar Skull Fracture - Defect in Cribiform Plate Immunologic - Splenectomy (P, H) - Complement Deficiency (M) - Immunoglobulin Deficiency (M, ?H)

Chemoprophylaxis of Bacterial Meningitis Meningococcal [Household or intimate contacts] Rifampin: adults, 600 mg q12h for 2 d; children <1 mo, 5 mg/kg q12h for 2 d; children >1 mo, 10 mg/kg for 2 d. Ciprofloxacin: adults, 500 mg, single dose. Ceftriaxone: children <15 yr, 125 mg, single IM dose; adults, 250 mg. Hemophilus influenzae [? Household or intimate contacts] Rifampin, 20 mg/kg/day for 4 days (not over 600 mg/dose). Recommended for household and ?day-care contacts if exposed to index case during week before onset. Use questionable if no one in household is younger than 4 yr. Pneumococcal [? Institutional (prisons) contacts] Penicillin prophylaxis considered for high-risk patients (ie, postsplenectomy patients)

Immunoprophylaxis of Bacterial Meningitis Meningococcal Monovalent A, monovalent C, bivalent A-C, or quadrivalent A, C, Y and W-135 vaccine. Vaccination should be considered an adjunct to antibiotic chemoprophylaxis for household or intimate contacts of patients when appropriate serogroups are causing disease. Consider prospective use with complement deficiency. Hemophilus Influenzae Haemophilus influenzae Type b Conjugate Vaccines Pneumococcal 7-valent pneumococcal conjugate vaccine (PCV; Prevnar). Covers the seven serotypes most commonly found in children and most commonly associated with drug resistance. 23 valent capsular polysaccharide vaccine for high risk patients (eg CSF leak, complement deficiency)