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. [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.
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 |
Adjunctive Dexamethasone Therapy
- Evidences for beneficial effects of dexamethasone are variable.
- Adjunctive use of dexamethasone for bacterial meningitis in selected groups may be associated with an improved survival or prognosis.[6][7][8][9][10][11] However, other studies fail to demonstrate a substantial reduction of death or neurological disability.[3][12][13][14] The occurrence of delayed cerebral thrombosis with dexamethasone therapy has been reported.[15]
- In infants and children with Haemophilus influenzae type b meningitis, the IDSA Practice Guideline supports the use of adjunctive Dexamethasone at 0.15 mg/kg q6h for 2—4 days with the first dose administered 10—20 minutes prior to, or at least concomitant with, the first antimicrobial dose.[16]
- In adults with suspected or proven Streptococcus pneumoniae meningitis, the IDSA also recommends Dexamethasone at 0.15 mg/kg q6h for 2—4 days with the first dose administered 10—20 minutes prior to, or at least concomitant with, the first antimicrobial dose. Dexamethasone should only be continued either if the CSF Gram stain demonstrates Gram-positive diplococci or if blood or CSF cultures are positive for S. pneumoniae. In this scenario, certain authorities advocate the addition of rifampin to the empirical combination of vancomycin plus a third-generation cephalosporin pending culture results and in vitro susceptibility testing.[16][17]
- Dexamethasone should not be administered to patients who have already received animicrobial therapy because it is unlikely to improve clinical outcome.[16]
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) - ↑ 3.0 3.1 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) - ↑ Lebel, MH.; Freij, BJ.; Syrogiannopoulos, GA.; Chrane, DF.; Hoyt, MJ.; Stewart, SM.; Kennard, BD.; Olsen, KD.; McCracken, GH. (1988). "Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials". N Engl J Med. 319 (15): 964–71. doi:10.1056/NEJM198810133191502. PMID 3047581. Unknown parameter
|month=ignored (help) - ↑ Odio, CM.; Faingezicht, I.; Paris, M.; Nassar, M.; Baltodano, A.; Rogers, J.; Sáez-Llorens, X.; Olsen, KD.; McCracken, GH. (1991). "The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis". N Engl J Med. 324 (22): 1525–31. doi:10.1056/NEJM199105303242201. PMID 2027357. Unknown parameter
|month=ignored (help) - ↑ Thwaites, GE.; Nguyen, DB.; Nguyen, HD.; Hoang, TQ.; Do, TT.; Nguyen, TC.; Nguyen, QH.; Nguyen, TT.; Nguyen, NH. (2004). "Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults". N Engl J Med. 351 (17): 1741–51. doi:10.1056/NEJMoa040573. PMID 15496623. Unknown parameter
|month=ignored (help) - ↑ Brouwer, MC.; Heckenberg, SG.; de Gans, J.; Spanjaard, L.; Reitsma, JB.; van de Beek, D. (2010). "Nationwide implementation of adjunctive dexamethasone therapy for pneumococcal meningitis". Neurology. 75 (17): 1533–9. doi:10.1212/WNL.0b013e3181f96297. PMID 20881273. Unknown parameter
|month=ignored (help) - ↑ Fritz, D.; Brouwer, MC.; van de Beek, D. (2012). "Dexamethasone and long-term survival in bacterial meningitis". Neurology. 79 (22): 2177–9. doi:10.1212/WNL.0b013e31827595f7. PMID 23152589. Unknown parameter
|month=ignored (help) - ↑ Peltola, H.; Roine, I.; Fernández, J.; Zavala, I.; Ayala, SG.; Mata, AG.; Arbo, A.; Bologna, R.; Miño, G. (2007). "Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled trial". Clin Infect Dis. 45 (10): 1277–86. doi:10.1086/522534. PMID 17968821. Unknown parameter
|month=ignored (help) - ↑ Peltola, H.; Roine, I.; Fernández, J.; González Mata, A.; Zavala, I.; Gonzalez Ayala, S.; Arbo, A.; Bologna, R.; Goyo, J. (2010). "Hearing impairment in childhood bacterial meningitis is little relieved by dexamethasone or glycerol". Pediatrics. 125 (1): e1–8. doi:10.1542/peds.2009-0395. PMID 20008417. Unknown parameter
|month=ignored (help) - ↑ Nguyen, TH.; Tran, TH.; Thwaites, G.; Ly, VC.; Dinh, XS.; Ho Dang, TN.; Dang, QT.; Nguyen, DP.; Nguyen, HP. (2007). "Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis". N Engl J Med. 357 (24): 2431–40. doi:10.1056/NEJMoa070852. PMID 18077808. Unknown parameter
|month=ignored (help) - ↑ Molyneux, EM.; Walsh, AL.; Forsyth, H.; Tembo, M.; Mwenechanya, J.; Kayira, K.; Bwanaisa, L.; Njobvu, A.; Rogerson, S. (2002). "Dexamethasone treatment in childhood bacterial meningitis in Malawi: a randomised controlled trial". Lancet. 360 (9328): 211–8. PMID 12133656. Unknown parameter
|month=ignored (help) - ↑ Schut, ES.; Brouwer, MC.; de Gans, J.; Florquin, S.; Troost, D.; van de Beek, D. (2009). "Delayed cerebral thrombosis after initial good recovery from pneumococcal meningitis". Neurology. 73 (23): 1988–95. doi:10.1212/WNL.0b013e3181c55d2e. PMID 19890068. Unknown parameter
|month=ignored (help) - ↑ 16.0 16.1 16.2 16.3 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: 15494903
- ↑ van de Beek D, de Gans J, Tunkel AR, Wijdicks EF (2006) Community-acquired bacterial meningitis in adults. N Engl J Med 354 (1):44-53. DOI:10.1056/NEJMra052116 PMID: 16394301