Bacterial meningitis medical therapy
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Bacterial meningitis Microchapters |
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Diagnosis |
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Treatment |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[3]
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.
Medical therapy
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.[1]
- 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.[2]
- 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).
| 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 |
Duration of Antimicrobial Therapy
- The duration of therapy in patients with bacterial meningitis has not been well-supported by evidence-based data.
- The IDSA Practice Guideline provides recommendations on the duration of antimicrobial agents based on microorganisms (see table below). However, the duration of antimicrobial therapy should be individualized in accordance with patient's clinical response.
- Maximum parenteral dosage should be maintained throughout the recommended duration of therapy to ensure adequate bactericidal concentrations are attained since antimicrobial entry attenuates as meningeal inflammation subsides, especially when dexamethasone is co-administered.
| Microorganism | Duration of Therapy |
| ▸ Neisseria meningitidis | 7 days |
| ▸ Haemophilus influenzae | 7 days |
| ▸ Streptococcus pneumoniae | 10—14 days |
| ▸ Streptococcus agalactiae | 14—21 days |
| ▸ Aerobic Gram-negative bacilli | 21 days |
| ▸ Listeria monocytogenes | ≥21 days |
References
- ↑ Andes, DR.; Craig, WA. (1999). "Pharmacokinetics and pharmacodynamics of antibiotics in meningitis". Infect Dis Clin North Am. 13 (3): 595–618. PMID 10470557. Unknown parameter
|month=ignored (help) - ↑ Nau, R.; Sörgel, F.; Eiffert, H. (2010). "Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections". Clin Microbiol Rev. 23 (4): 858–83. doi:10.1128/CMR.00007-10. PMID 20930076. Unknown parameter
|month=ignored (help) - ↑ van de Beek, D.; Drake, JM.; Tunkel, AR. (2010). "Nosocomial bacterial meningitis". N Engl J Med. 362 (2): 146–54. doi:10.1056/NEJMra0804573. PMID 20071704. Unknown parameter
|month=ignored (help) - ↑ Rodríguez Guardado, A.; Blanco, A.; Asensi, V.; Pérez, F.; Rial, JC.; Pintado, V.; Bustillo, E.; Lantero, M.; Tenza, E. (2008). "Multidrug-resistant Acinetobacter meningitis in neurosurgical patients with intraventricular catheters: assessment of different treatments". J Antimicrob Chemother. 61 (4): 908–13. doi:10.1093/jac/dkn018. PMID 18281693. Unknown parameter
|month=ignored (help) - ↑ Cruciani, M.; Navarra, A.; Di Perri, G.; Andreoni, M.; Danzi, MC.; Concia, E.; Bassetti, D. (1992). "Evaluation of intraventricular teicoplanin for the treatment of neurosurgical shunt infections". Clin Infect Dis. 15 (2): 285–9. PMID 1387805. Unknown parameter
|month=ignored (help) - ↑ Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM et al. (2004) Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 39 (9):1267-84. DOI:10.1086/425368 PMID: [1]