Sandbox/v46

	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]

Overview

Acute bacterial meningitis is a medical emergency; commence empiric treatment after obtaining blood and/or cerebrospinal fluid (CSF) cultures if the possibility of bacterial meningitis becomes evident. Once a bacterial etiology has been identified on a CSF Gram stain, treatment regimen should be optimized accordingly. Further modifications may be required after the culture and/or in vitro susceptibility results are available. Neuroimaging (such as CT scan and MRI) or lumbar puncture must not delay antimicrobial 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).

*Recommended Doses of Antimicrobial Agents via 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
▸ 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.

*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]

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.^[6]^[17]

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

▸ Newborns, Age <1 Week

▸ Newborns, Age 1—4 Weeks

▸ Infants & Children

▸ Adults, Age <50 Years

▸ Adults, Age >50 Years

▸ Immunocompromised

▸ Recurrent

Nosocomial

▸ 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

CSF Gram Stain-Based Therapy Adapted from Lancet. 2012;380(9854):1693-702.^[18] and Clin Infect Dis. 2004;39(9):1267-84.^[6]

Gram-Positive

▸ Gram-Positive Cocci in Chains

▸ Gram-Positive Cocci in Pairs

▸ Gram-Positive (Cocco-)Bacilli

Gram-Negative

▸ Gram-Negative Cocci in Pairs

▸ Gram-Negative Coccobacilli

▸ Gram-Negative Bacilli

Gram-Positive Cocci in Chains
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
▸ Meropenem 2 g IV q8h OR ▸ Moxifloxacin 400 mg IV q24h

Gram-Positive Cocci in Pairs
Preferred Regimen
▸ Ampicillin 2 g IV q4h OR ▸ Penicillin G 4 MU IV q4h
PLUS
▸ Gentamicin 1.7 mg/kg IV q8h
Alternative Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h

Gram-Positive (Cocco-)Bacilli
Preferred Regimen
▸ Ampicillin 2 g IV q4h OR ▸ Penicillin G 4 MU IV q4h
PLUS
▸ Gentamicin 1.7 mg/kg IV q8h
Alternative Regimen
▸ TMP/SMZ 5 mg/kg IV q6—12h (TMP component) OR ▸ Meropenem 2 g IV q8h

Gram-Negative Cocci in Pairs
Preferred Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h
Alternative Regimen
▸ Penicillin G 4 MU IV q4h OR ▸ Ampicillin 2 g IV q4h OR ▸ Chloramphenicol 1—1.5 g IV q6h OR ▸ Moxifloxacin 400 mg IV q24h OR ▸ Aztreonam 2 g IV q6—8h

Gram-Negative Coccobacilli
Preferred Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h
Alternative Regimen
▸ Chloramphenicol 1—1.5 g IV q6h OR ▸ Cefepime 2 g IV q8h OR ▸ Meropenem 2 g IV q8h OR ▸ Moxifloxacin 400 mg IV q24h

Gram-Negative Bacilli
Preferred Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h
Alternative Regimen
▸ Cefepime 2 g IV q8h OR ▸ Meropenem 2 g IV q8h OR ▸ Aztreonam 2 g IV q6—8h OR ▸ Moxifloxacin 400 mg IV q24h OR ▸ TMP/SMZ 5 mg/kg IV q6—12h (TMP component)

Pathogen-Based Therapy Adapted from Lancet. 2012;380(9854):1693-702.^[18] and Clin Infect Dis. 2004;39(9):1267-84.^[6]

Bacteria

▸ Acinetobacter baumannii

▸ Enterobacteriaceae

▸ Haemophilus influenzae

▸ Listeria monocytogenes

▸ Neisseria meningitidis

▸ Pseudomonas aeruginosa

▸ Staphylococcus aureus

▸ Staphylococcus epidermidis

▸ Streptococcus agalactiae

▸ Streptococcus pneumoniae

Acinetobacter baumannii
Preferred Regimen
▸ Meropenem 2 g IV q8h
Alternative Regimen
▸ Colistin 1.25 mg/kg IV q6—12h OR ▸ Polymyxin B 0.75—1.25 mg/kg IV q12h

Enterobacteriaceae
Preferred Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h
Alternative Regimen
▸ Aztreonam 2 g IV q6—8h OR ▸ Moxifloxacin 400 mg IV q24h OR ▸ TMP/SMZ 5 mg/kg IV q6—12h (TMP component) OR ▸ Meropenem 2 g IV q8h OR ▸ Ampicillin 2 g IV q4h

H. influenzae, β-lactamase Negative
Preferred Regimen
▸ Ampicillin 2 g IV q4h
Alternative Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h OR ▸ Cefepime 2 g IV q8h OR ▸ Chloramphenicol 1—1.5 g IV q6h OR ▸ Aztreonam 2 g IV q6—8h OR ▸ Moxifloxacin 400 mg IV q24h
H. influenzae, β-lactamase Positive
Preferred Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h
Alternative Regimen
▸ Cefepime 2 g IV q8h OR ▸ Chloramphenicol 1—1.5 g IV q6h OR ▸ Aztreonam 2 g IV q6—8h OR ▸ Moxifloxacin 400 mg IV q24h
H. influenzae, β-lactamase Negative, Ampicillin Resistant
Preferred Regimen
▸ Meropenem 2 g IV q8h
Alternative Regimen
▸ Moxifloxacin 400 mg IV q24h

Listeria monocytogenes
Preferred Regimen
▸ Ampicillin 2 g IV q4h OR ▸ Penicillin G 4 MU IV q4h
PLUS
▸ Gentamicin 1.7 mg/kg IV q8h
Alternative Regimen
▸ TMP/SMZ 5 mg/kg IV q6—12h (TMP component)

N. meningitidis, Penicillin MIC <0.1 μg/mL
Preferred Regimen
▸ Penicillin G 4 MU IV q4h OR ▸ Ampicillin 2 g IV q4h
Alternative Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h OR ▸ Chloramphenicol 1—1.5 g IV q6h
N. meningitidis, Penicillin MIC ≥0.1 μg/mL
Preferred Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h
Alternative Regimen
▸ Cefepime 2 g IV q8h OR ▸ Chloramphenicol 1—1.5 g IV q6h OR ▸ Moxifloxacin 400 mg IV q24h OR ▸ Meropenem 2 g IV q8h

Pseudomonas aeruginosa
Preferred Regimen
▸ Ceftazidime 2 g IV q8h OR ▸ Cefepime 2 g IV q8h
PLUS
▸ Gentamicin 1.7 mg/kg IV q8h
Alternative Regimen
▸ Aztreonam 2 g IV q6—8h OR ▸ Meropenem 2 g IV q8h OR ▸ Ciprofloxacin 400 mg IV q8—12h
PLUS
▸ Gentamicin 1.7 mg/kg IV q8h

Staphylococcus aureus, Methicillin sensitive
Preferred Regimen
▸ Nafcillin 1.5—2 g IV q4h OR ▸ Oxacillin 1.5—2 g IV q4h
Alternative Regimen
▸ Vancomycin 15 mg/kg IV q6h (trough 15—20 μg/mL) OR ▸ Linezolid 600 mg IV q12h OR ▸ Daptomycin 6 mg/kg IV q24h
Staphylococcus aureus, Methicillin resistant
Preferred Regimen
▸ Vancomycin 15 mg/kg IV q6h (trough 15—20 μg/mL)
PLUS
▸ Rifampin 600 mg IV q24h
Alternative Regimen
▸ TMP/SMZ 5 mg/kg IV q6—12h (TMP component) OR ▸ Linezolid 600 mg IV q12h OR ▸ Daptomycin 6 mg/kg IV q24h
PLUS
▸ Rifampin 600 mg IV q24h

Staphylococcus epidermidis
Preferred Regimen
▸ Vancomycin 15 mg/kg IV q6h (trough 15—20 μg/mL)
PLUS
▸ Rifampin 600 mg IV q24h
Alternative Regimen
▸ Linezolid 600 mg IV q12h
PLUS
▸ Rifampin 600 mg IV q24h

Streptococcus agalactiae
Preferred Regimen
▸ Ampicillin 2 g IV q4h OR ▸ Penicillin G 4 MU IV q4h
PLUS
▸ Gentamicin 1.7 mg/kg IV q8h
Alternative Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h OR ▸ Vancomycin 15 mg/kg IV q6h (trough 15—20 μg/mL)

S. pneumoniae, Penicillin MIC ≤0.06 μg/mL
Preferred Regimen
▸ Penicillin G 4 MU IV q4h OR ▸ Ampicillin 2 g IV q4h
Alternative Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h OR ▸ Chloramphenicol 1—1.5 g IV q6h
S. pneumoniae, Penicillin MIC ≥0.12 μg/mL, Cefotaxime/Ceftriaxone MIC <1.0 μg/mL
Preferred Regimen
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h
Alternative Regimen
▸ Cefepime 2 g IV q8h OR ▸ Meropenem 2 g IV q8h
S. pneumoniae, Penicillin MIC ≥0.12 μg/mL, Cefotaxime/Ceftriaxone MIC ≥1.0 μg/mL
Preferred Regimen
▸ Vancomycin 15 mg/kg IV q6h (trough 15—20 μg/mL)
PLUS
▸ Cefotaxime 2 g IV q4—6h OR ▸ Ceftriaxone 2 g IV q12h
PLUS
▸ Rifampin 600 mg IV q24h
Alternative Regimen
▸ Vancomycin 15 mg/kg IV q6h (trough 15—20 μg/mL)
PLUS
▸ Moxifloxacin 400 mg IV q24h

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 ^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)
↑ 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)
↑ ^6.0 ^6.1 ^6.2 ^6.3 ^6.4 ^6.5 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]
↑ 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)
↑ 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
↑ ^18.0 ^18.1 ^18.2 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)

[Andes-1999-1] 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)

[Nau-2010-2] 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)

[van_de_Beek-2010-3] 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)

[Rodríguez_Guardado-2008-4] 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)

[Cruciani-1992-5] 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)

[pmid15494903-6] 6.0 ^6.1 ^6.2 ^6.3 ^6.4 ^6.5 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]

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[van_de_Beek-2012-18] 18.0 ^18.1 ^18.2 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)

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