Meningitis medical therapy: Difference between revisions

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|+ <SMALL>''Recommended Doses of Selected Antimicrobial Agents Administered by the Intraventricular Route.''<ref name="van de Beek-2010">{{Cite journal  | last1 = van de Beek | first1 = D. | last2 = Drake | first2 = JM. | last3 = Tunkel | first3 = AR. | title = Nosocomial bacterial meningitis. | journal = N Engl J Med | volume = 362 | issue = 2 | pages = 146-54 | month = Jan | year = 2010 | doi = 10.1056/NEJMra0804573 | PMID = 20071704 }}</ref><ref name="Rodríguez Guardado-2008">{{Cite journal  | last1 = Rodríguez Guardado | first1 = A. | last2 = Blanco | first2 = A. | last3 = Asensi | first3 = V. | last4 = Pérez | first4 = F. | last5 = Rial | first5 = JC. | last6 = Pintado | first6 = V. | last7 = Bustillo | first7 = E. | last8 = Lantero | first8 = M. | last9 = Tenza | first9 = E. | title = Multidrug-resistant Acinetobacter meningitis in neurosurgical patients with intraventricular catheters: assessment of different treatments. | journal = J Antimicrob Chemother | volume = 61 | issue = 4 | pages = 908-13 | month = Apr | year = 2008 | doi = 10.1093/jac/dkn018 | PMID = 18281693 }}</ref><ref name="Cruciani-1992">{{Cite journal  | last1 = Cruciani | first1 = M. | last2 = Navarra | first2 = A. | last3 = Di Perri | first3 = G. | last4 = Andreoni | first4 = M. | last5 = Danzi | first5 = MC. | last6 = Concia | first6 = E. | last7 = Bassetti | first7 = D. | title = Evaluation of intraventricular teicoplanin for the treatment of neurosurgical shunt infections. | journal = Clin Infect Dis | volume = 15 | issue = 2 | pages = 285-9 | month = Aug | year = 1992 | doi =  | PMID = 1387805 }}</ref></SMALL>
|+ <SMALL>''Recommended Doses of Selected Antimicrobial Agents Administered by the Intraventricular Route.''<ref name="van de Beek-2010">{{Cite journal  | last1 = van de Beek | first1 = D. | last2 = Drake | first2 = JM. | last3 = Tunkel | first3 = AR. | title = Nosocomial bacterial meningitis. | journal = N Engl J Med | volume = 362 | issue = 2 | pages = 146-54 | month = Jan | year = 2010 | doi = 10.1056/NEJMra0804573 | PMID = 20071704 }}</ref><ref name="Rodríguez Guardado-2008">{{Cite journal  | last1 = Rodríguez Guardado | first1 = A. | last2 = Blanco | first2 = A. | last3 = Asensi | first3 = V. | last4 = Pérez | first4 = F. | last5 = Rial | first5 = JC. | last6 = Pintado | first6 = V. | last7 = Bustillo | first7 = E. | last8 = Lantero | first8 = M. | last9 = Tenza | first9 = E. | title = Multidrug-resistant Acinetobacter meningitis in neurosurgical patients with intraventricular catheters: assessment of different treatments. | journal = J Antimicrob Chemother | volume = 61 | issue = 4 | pages = 908-13 | month = Apr | year = 2008 | doi = 10.1093/jac/dkn018 | PMID = 18281693 }}</ref><ref name="Cruciani-1992">{{Cite journal  | last1 = Cruciani | first1 = M. | last2 = Navarra | first2 = A. | last3 = Di Perri | first3 = G. | last4 = Andreoni | first4 = M. | last5 = Danzi | first5 = MC. | last6 = Concia | first6 = E. | last7 = Bassetti | first7 = D. | title = Evaluation of intraventricular teicoplanin for the treatment of neurosurgical shunt infections. | journal = Clin Infect Dis | volume = 15 | issue = 2 | pages = 285-9 | month = Aug | year = 1992 | doi =  | PMID = 1387805 }}</ref></SMALL>
| style="background: #A5B2D6; border: 0px solid #696969; padding: 0 5px; width: 200px"| '''Antimicrobial Agent''' || style="background: #A5B2D6; border: 0px solid #696969; padding: 0 5px; width: 400px" | '''Daily Intraventricular Dose'''
| style="background: #A5B2D6; border: 0px solid #696969; padding: 0 5px; width: 200px"| '''Antimicrobial Agent''' || style="background: #A5B2D6; border: 0px solid #696969; padding: 0 5px; width: 200px" | '''Daily Intraventricular Dose'''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Vancomycin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''5—20 mg/day''''' <SMALL>(or '''''10—20 mg/day''''')</SMALL>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Vancomycin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''5—20 mg'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Gentamicin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''4—8 mg/day''''' <SMALL>('''''1—2 mg/day''''' in infants and children)</SMALL>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Gentamicin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''4—8 mg'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Tobramycin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''5—20 mg/day'''''
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Tobramycin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''5—20 mg'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Amikacin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''5—50 mg/day''''' <SMALL>(usual dose is '''''30 mg/day''''')</SMALL>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Amikacin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''5—50 mg'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Polymyxin B]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''5 mg/day''''' <SMALL>('''''1—2 mg/day''''' in infants and children)</SMALL>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Polymyxin B]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''5 mg'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Colistimethate sodium]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''10 mg q24h''''' <SMALL>(or '''''5—10 mg q12h''''')</SMALL>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Colistimethate sodium]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''10 mg'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Quinupristin dalfopristin|Quinupristin/Dalfopristin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''2—5 mg/day'''''
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Quinupristin dalfopristin|Quinupristin/Dalfopristin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''2—5 mg'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Teicoplanin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''5—40 mg/day'''''
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Teicoplanin]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''5—40 mg'''''
|-
|-
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Amphotericin B]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''0.1—0.5 mg/day''''' <SMALL>(for ''Candida'' shunt infection)</SMALL>
| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Amphotericin B]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''0.1—0.5 mg/day'''''
|-
|-
|}
|}

Revision as of 16:39, 22 January 2014

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. [2]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [3], Sheng Shi, M.D. [4]

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
 ▸ Gentamicin 4—8 mg
 ▸ Tobramycin 5—20 mg
 ▸ Amikacin 5—50 mg
 ▸ Polymyxin B 5 mg
 ▸ Colistimethate sodium 10 mg
 ▸ Quinupristin/Dalfopristin 2—5 mg
 ▸ Teicoplanin 5—40 mg
 ▸ Amphotericin B 0.1—0.5 mg/day


Duration of Antimicrobial Therapy

Recommended Duration of Antimicrobial Therapy Based on Isolated Pathogen.[6]
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


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.[7][8][9][10][11][12] However, other studies fail to demonstrate a substantial reduction of death or neurological disability.[3][13][14][15] The occurrence of delayed cerebral thrombosis with dexamethasone therapy has been reported.[16]
  • 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.[6]
  • Dexamethasone should not be given to patients who have already received animicrobial therapy because it is unlikely to improve clinical outcome.[6]


Empiric Therapy Adapted from Lancet. 2012;380(9854):1693-702.[18] and N Engl J Med. 2010;362(2):146-54.[3]

Community-Acquired Meningitis
  ▸  Newborns, Age <1 Week
  ▸  Newborns, Age 1—4 Weeks
  ▸  Infants & Children
  ▸  Adults, Age <50 Years
  ▸  Adults, Age >50 Years
  ▸  Immunocompromised
  ▸  Recurrent
  Nosocomial Meningitis
  ▸  Postneurosurgical Infection
  ▸  CSF Shunt Infection
  ▸  Penetrating Trauma
  ▸  Basilar Skull Fracture
Newborns, Age <1 Week
Preferred Regimen
Ampicillin 50 mg/kg IV q8h
PLUS
Cefotaxime 50 mg/kg IV q8—12h
Alternative Regimen
Ampicillin 50 mg/kg IV q8h
PLUS
Gentamicin 2.5 mg/kg IV q12h
Newborns, Age 1—4 Weeks
Preferred Regimen
Ampicillin 200 mg/kg/day IV q6—8h
PLUS
Cefotaxime 50 mg/kg 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
Infants & Children
Preferred Regimen
Vancomycin 15 mg/kg IV q6h (trough 15—20 μg/mL)
PLUS
Cefotaxime 75 mg/kg IV q6—8h
OR
Ceftriaxone 80—100 mg/kg/day IV q12—24h
Alternative Regimen
Vancomycin 15 mg/kg IV q6h (trough 15—20 μg/mL)
PLUS
Meropenem 40 mg/kg IV q8h
Add Ampicillin 75 mg/kg IV q6h if suspecting Listeria monocytogenes.
Adults, Age <50 Years
Preferred Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Cefotaxime 2 g IV q4—6h
OR
Ceftriaxone 2 g IV q12h
Alternative Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Meropenem 2 g IV q8h
Add Ampicillin 2 g IV q4h if suspecting Listeria monocytogenes.
Adults, Age >50 Years
Preferred Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Cefotaxime 2 g IV q4—6h
OR
Ceftriaxone 2 g IV q12h
PLUS
Ampicillin 2 g IV q4h
Alternative Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Aztreonam 2 g IV q6—8h
PLUS
TMP/SMZ 5 mg/kg IV q6—12h (TMP component)
Immunocompromised
Preferred Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Cefepime 2 g IV q8h
OR
Meropenem 2 g IV q8h
PLUS
Ampicillin 2 g IV q4h
Recurrent
Preferred Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Cefotaxime 2 g IV q4—6h
OR
Ceftriaxone 2 g IV q12h
Postneurosurgical Infection
Preferred Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Cefepime 2 g IV q8h
OR
Ceftazidime 2 g IV q8h
OR
Meropenem 2 g IV q8h
Alternative Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Aztreonam 2 g IV q6—8h
OR
Ciprofloxacin 400 mg IV q8—12h
CSF Shunt Infection
Preferred Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Cefepime 2 g IV q8h
OR
Ceftazidime 2 g IV q8h
OR
Meropenem 2 g IV q8h
Alternative Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Aztreonam 2 g IV q6—8h
OR
Ciprofloxacin 400 mg IV q8—12h
Penetrating Trauma
Preferred Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Cefepime 2 g IV q8h
OR
Ceftazidime 2 g IV q8h
OR
Meropenem 2 g IV q8h
Alternative Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Aztreonam 2 g IV q6—8h
OR
Ciprofloxacin 400 mg IV q8—12h
Basilar Skull Fracture
Preferred Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Cefotaxime 2 g IV q4—6h
OR
Ceftriaxone 2 g IV q12h
Alternative Regimen
Vancomycin 15 mg/kg IV q8—12h (trough 15—20 μg/mL)
PLUS
Aztreonam 2 g IV q6—8h
OR
Ciprofloxacin 400 mg IV q8—12h


Pathogen-Based Therapy

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 3.2 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. 6.0 6.1 6.2 6.3 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: [1]
  7. 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)
  8. 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)
  9. 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)
  10. 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)
  11. 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)
  12. 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)
  13. 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)
  14. 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)
  15. 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)
  16. 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)
  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)