Bacterial meningitis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]

Overview

Acute bacterial meningitis is a medical emergency. Empiric antimicrobial therapy must be administered after obtaining blood and/or cerebrospinal fluid (CSF) cultures in cases of suspected meningitis. Once a bacterial etiology has been identified on a CSF Gram stain, treatment regimen should be individualized accordingly. Neither neuroimaging (such as CT scan and MRI) nor lumbar puncture should delay the administration of antimicrobial therapy. For neonates (age < 1 month), empirical antimicrobial therapy generally includes Ampicillin 12 g/day IV q4h AND (Cefotaxime 8–12 g/day q4–6h OR Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h). For children older than 1 month and adults < 50 years, the preferred regimen is usually Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h). For adults ≥ 50 years of age, Ampicillin 12g/day IV q4h is added to the usual adult regimen. The duration of therapy is variable depending on the causative pathogen, but generally the duration is between 1-3 weeks. Adjunctive Dexamethasone at a dose of 0.15 mg/kg q6h for 2—4 days may be effective when administered early (0-20 minutes prior to administration of antimicrobial therapy) among pediatric patients with H. influenzae meningitis and among adults with S. pneumoniae meningitis.

Principles of Therapy for Bacterial Meningitis

Factors Determining Antimicrobial Activity

• Factors determine the acitivity of antimicrobial agents include pharmacodynamics, pharmacokinetics, penetration into the CSF, and bactericidal activity within the CSF.

• Beta-lactams, aminoglycosides, glycopeptides, linezolid, and daptomycin are considered to have poor penetration into the CSF, while fluoroquinolones, chloramphenicol, aztreonam, and tigecycline generally achieve minimum inhibitory concentration (MIC) in the CSF at standard dosage.

• Aminoglycosides and fluoroquinolones express a concentration-dependent manner of bactericidal activity; beta-lactams typically follow a a time-dependent antimicrobial pattern (i.e., the activity is dependent on the time that CSF concentration exceeds MIC as a proportion of the dosing interval).

• Penetration into the CSF is less prominent for drugs with a high molecular weight, high protein-binding ability, low lipid solubility, and drugs that are subject to active transport in the choroid plexus such as penicillins and cephalosporins. Toxicity due to dose escalation may limit the usage the aminoglycosides, glycopeptides, and polymyxins, thus intrathecal or intraventricular administration might be occasionally required (see table below).

Recommended Doses of Antimicrobial Agents via the Intraventricular Route.

Antimicrobial Agent	Daily Intraventricular Dose
▸ Vancomycin	5—20 mg
▸ Gentamicin	4—8 mg
▸ Tobramycin	5—20 mg
▸ Amikacin	5—50 mg
▸ Polymyxin B	5 mg
▸ Colistin	10 mg
▸ Quinupristin/Dalfopristin	2—5 mg
▸ Teicoplanin	5—40 mg
▸ Amphotericin B	0.1—0.5 mg/day

References

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