Meningitis medical therapy

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Meningitis Main Page

Patient Information

Overview

Causes

Classification

Viral Meningitis
Bacterial Meningitis
Fungal Meningitis

Differential Diagnosis

Diagnosis

Treatment

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.

Factors Determining Antimicrobial Activity

  • 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.


Recommended Doses of Selected Antimicrobial Agents Administered by the Intraventricular Route.[3][4][5]
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]
  • 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
Newborn, Age <1 Week
Preferred Regimen
Ampicillin 50 mg/kg IV q8h
PLUS
Cefotaxime 100—150 mg/kg/day IV q8—12h
Alternative Regimen
Ampicillin 50 mg/kg IV q8h
PLUS
Gentamicin 2.5 mg/kg IV q12h
Newborn, Age 1—4 Weeks
Preferred Regimen
Ampicillin 200 mg/kg/day IV q6—8h
PLUS
Cefotaxime 150—200 mg/kg/day IV q6—8h
Alternative Regimen
Ampicillin 200 mg/kg/day IV q6—8h
PLUS
Gentamicin 2.5 mg/kg IV q8h
OR
Tobramycin 2.5 mg/kg IV q8h
OR
Amikacin 10 mg/kg IV q8h
Infant & Children
Preferred Regimen
Vancomycin 15 mg/kg IV q6h (Target trough concentration: 15—20 μg/mL)
PLUS
Cefotaxime 225—300 mg/kg/day IV q6—8h
OR
Ceftriaxone 80—100 mg/kg/day IV q12—24h
  Add Ampicillin 50 mg/kg IV q6h if Listeria monocytogenes is also suspected.
Adult, Age <50 Years
Preferred Regimen
Vancomycin 30—60 mg/kg/day IV q8—12h (Target trough concentration: 15—20 μg/mL)
PLUS
Cefotaxime 8—12 g/day IV q4—6h
OR
Ceftriaxone 2 g IV q12h
  Add Ampicillin 2 g IV q4h if Listeria monocytogenes is also suspected.
Adult, Age >50 Years
Preferred Regimen
Vancomycin 30—60 mg/kg/day IV q8—12h (Target trough concentration: 15—20 μg/mL)
PLUS
Ampicillin 2 g IV q4h
PLUS
Cefotaxime 8—12 g/day IV q4—6h
OR
Ceftriaxone 2 g IV q12h
Immunocompromised
Preferred Regimen
Vancomycin 30—60 mg/kg/day IV q8—12h (Target trough concentration: 15—20 μg/mL)
PLUS
Ampicillin 2 g IV q4h
PLUS
Cefepime 2 g IV q8h
OR
Meropenem 2 g IV q8h
Recurrent
Preferred Regimen
Vancomycin 30—60 mg/kg/day IV q8—12h (Target trough concentration: 15—20 μg/mL)
PLUS
Cefotaxime 8—12 g/day IV q4—6h
OR
Ceftriaxone 2 g IV q12h
  Nosocomial Bacterial Meningitis
 ▸   Postneurosurgical Infection
 ▸   CSF Shunt Infection
 ▸   Penetrating Trauma
 ▸   Basilar Skull Fracture
Postsurgical Infection
Preferred Regimen
Vancomycin 15 mg/kg IV q8—12h (Target trough concentration: 15—20 μg/mL)
PLUS
Cefepime 2 g IV q8h
OR
Ceftazidime 2 g IV q8h
OR
Meropenem 2 g IV q8h
CSF Shunt Infection
Vancomycin 15 mg/kg IV q8—12h (Target trough concentration: 15—20 μg/mL)
PLUS
Cefepime 2 g IV q8h
OR
Ceftazidime 2 g IV q8h
OR
Meropenem 2 g IV q8h
Penetrating Trauma
Vancomycin 15 mg/kg IV q8—12h (Target trough concentration: 15—20 μg/mL)
PLUS
Cefepime 2 g IV q8h
OR
Ceftazidime 2 g IV q8h
OR
Meropenem 2 g IV q8h
Basilar Skull Fracture
Vancomycin 15 mg/kg IV q8—12h (Target trough concentration: 15—20 μg/mL)
PLUS
Ceftriaxone 2 g IV q12h
OR
Cefotaxime 2 g IV q4—6h

References

  1. 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)
  2. 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. 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)
  4. 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)
  5. 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)
  6. 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)
  7. 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)
  8. 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)
  9. 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)
  10. 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)
  11. 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)
  12. 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)
  13. 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)
  14. 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)
  15. 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. 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
  17. 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
  18. 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)