Meningitis medical therapy
Meningitis Main Page |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2], Sheng Shi, M.D. [3]
Principles of Therapy for Bacterial Meningitis
- Acute bacterial meningitis is a medical emergency; commence empiric treatment after obtaining blood and/or cerebrospinal fluid (CSF) cultures once the possibility of bacterial meningitis becomes evident. Antibiotic regimen should be adjusted according to the culture results.
- Neuroimaging (such as CT scan and MRI) or lumbar puncture must not delay antimicrobial therapy.
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, 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).
- Adequate parenteral dosage should be maintained throughout the course to ensure adequate bactericidal concentration since antimicrobial entry attenuates as meningeal inflammation subsides, especially when adjunctive dexamethasone is co-administered.
- 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/day; 10—20 mg/day has been used in most studies |
▸ Gentamicin | 4—8 mg/day in adults; 1—2 mg/day in infants and children |
▸ Tobramycin | 5—20 mg/day |
▸ Amikacin | 5—50 mg/day; the usual daily dose is 30 mg/day |
▸ Polymyxin B | 5 mg/day in adults; 1—2 mg/day in infants and children |
▸ Colistimethate sodium | 10 mg q24h or 5—10 mg q12h |
▸ Quinupristin/Dalfopristin | 2—5 mg/day |
▸ Teicoplanin | 5—40 mg/day; 5—10 mg q48—72h in one study |
Adjunctive Dexamethasone Therapy
- Evidences for beneficial effects of dexamethasone are variable. In some studies, adjunctive use of dexamethasone for bacterial meningitis in selected groups are 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 if the CSF Gram stain reveals 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 given to patients who have already receive animicrobial therapy because it is unlikely to improve clinical outcome.[16]
Empiric Therapy Adapted from Advances in treatment of bacterial meningitis. Lancet. 2012;380(9854):1693-702.[18]
Community-Acquired Meningitis
▸ Newborn, Age <1 Week
▸ Newborn, Age 1—4 Weeks
▸ Infant & Children
▸ Adult, Age <50 Years
▸ Adult, Age >50 Years
▸ Immunocompromised
▸ Recurrent
|
|
Healthcare-Associated Meningitis
▸ Basilar Skull Fracture
▸ Head Trauma; Post-Neurosurgery
|
|
Pathogen-Based Therapy
Streptococcus pneumoniae
|
|
Neisseria meningitidis
|
|
Listeria monocytogenes and Streptococcus agalactiae
|
|
Haemophilus influenzae
|
|
Staphylococcus aureus
|
|
Staphylococcus epidermidis and Acinetobacter baumanniiΩ
|
|
Enterobacteriaceae and Pseudomonas aeruginosa
|
|
† MIC = minimum inhibitory concentration.‡Addition of rifampicin can be considered if the organism is susceptible, the expected clinical or bacteriological response is delayed, or the cefotaxime/ceftriaxone MIC of the pneumococcal isolate is >4.0 μg/mL organism is susceptible, the expected clinical or bacteriological response is delayed, or the cefotaxime/ceftriaxone MIC.
Φ No clinical data exist for use of this agent in patients with pneumococcal meningitis; recommendation is based on cerebrospinal fluid penetration and in-vitro activity against S. pneumoniae.
£ Addition of an aminoglycoside should be considered; might need intraventricular or intrathecal administration in Gram-negative meningitis.
ǁ Addition of rifampicin should be considered.
Ω Choice of a specific agent should be based on in-vitro susceptibility testing.
†† Might also need to be administered by the intraventricular or intrathecal routes.
ǂ Might also need to be administered by the intraventricular or intrathecal routes.
₦ Addition of rifampicin should be considered.
Δ The fluoroquinolones gatifloxacin and moxifloxacin pene trate the CSF effectively and have greater in-vitro activity against Gram-positive bacteria than do their earlier counterparts (eg, ciprofloxacin). Findings from experi mental meningitis models suggested their efficacy in S. pneumoniae meningitis, including that caused by penicillin-resistant and cephalosporin-resistant strains. Although one controlled trial suggested the fluoroquinolone trovafl -oxacin mesilate to be as eff ective as ceftriaxone, with or without the addition of vancomycin, for paediatric bacterial meningitis, no clinical trials describe the use of gatifloxacin or moxifloxacin to treat bacterial meningitis in human beings. Trovafloxacin and gatifloxacin have been asso ciated with serious hepatic toxicity and dysglycaemia, respectively, and were with drawn from many markets. The IDSA guidelines recommend moxifloxacin as an alternative to third-generation cephalosporins plus vancomycin for meningitis caused by S. pneumoniae strains resistant to penicillin and third-generation cephalosporins, although some experts recom mend that this agent should not be used alone but rather should be combined with another drug (either vancomycin or a third-generation cephalosporin), because of the absence of clinical data supporting its use.
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 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
- ↑ van de Beek, D.; Brouwer, MC.; Thwaites, GE.; Tunkel, AR. (2012). "Advances in treatment of bacterial meningitis". Lancet. 380 (9854): 1693–702. doi:10.1016/S0140-6736(12)61186-6. PMID 23141618. Unknown parameter
|month=
ignored (help)