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]
Antimicrobial Agent Daily Intraventricular Dose
 ▸ Vancomycin 5–20 mg; 10 mg or 20 mg has been used in most studies.
 ▸ Gentamicin 4–8 mg in adults; 1–2 mg in infants and children
 ▸ Amikacin 5–50 mg; the usual daily dose is 30 mg.
 ▸ Polymyxin B 5 mg in adults; 1–2 mg in infants and children
 ▸ Colistimethate sodium 10 mg q24h or 5–10 mg q12h


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.[5][6][7][8][9][10] However, other studies fail to demonstrate a substantial reduction of death or neurological disability.[3][11][12][13] The occurrence of delayed cerebral thrombosis with dexamethasone therapy has been reported.[14]
  • 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.[15]
  • Dexamethasone should not be given to patients who have already receive animicrobial therapy because it is unlikely to improve clinical outcome.[15]

Empiric Therapy Adapted from Advances in treatment of bacterial meningitis. Lancet. 2012;380(9854):1693-702.[17]

  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
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 (50 mg/kg IV q6h for children) if meningitis caused by Listeria monocytogenes is also suspected.
Adult, Age >50 Years
Preferred Regimen
Vancomycin 30–60 mg/kg/day IV q8–12h
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
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
PLUS
Cefotaxime 8–12 g/day IV q4–6h
OR
Ceftriaxone 2 g IV q12h
  Healthcare-Associated Meningitis
 ▸   Basilar Skull Fracture
 ▸   Head Trauma; Post-Neurosurgery
Basilar Skull Fracture
Preferred Regimen
Vancomycin 30—60 mg/kg/day IV q8–12h
PLUS
Cefotaxime 8–12 g/day IV q4–6h
OR
Ceftriaxone 2 g IV q12h
Head Trauma; Post-Neurosurgery
Vancomycin 30—60 mg/kg/day IV q8–12h
PLUS
Ceftazidime 2 g IV q8 h
OR
Cefepime 2 g IV q8h
OR
Meropenem 2 g IV q8h

Pathogen-Based Therapy

Streptococcus pneumoniae
Penicillin MIC ≤0.06 μg/mL
Preferred Regimen
Penicillin G Low: 600,000–1.2 million units/day IM; High:≥ 20 million units IV q24h(=12 g)
OR
Ampicillin 150–200 mg/kg IV q3-4h
Alternative Regimen
Cefotaxime 1 g q8–12h to 2 g IV q4h
OR
Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine)
OR
Chloramphenicol 0.25–1 g po IV q6h to max. of 4 g/day
Penicillin MIC ≥0.12 μg/mL
Cefotaxime or Ceftriaxone MIC† <1.0 μg/mL
Preferred Regimen
Cefotaxime 1 g q8–12h to 2 g IV q4h
OR
Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine)
Alternative Regimen
Cefepime 1–2 g IV q12h
OR
Meropenem 2 g IV q8h
Cefotaxime or Ceftriaxone MIC† >1.0 μg/mL
Preferred Regimen
Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h (Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. )
AND
Cefotaxime 1 g q8–12h to 2 g IV q4h
OR
Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine)
Alternative Regimen
Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h (Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. )
AND
Moxifloxacin 400 mg po IV q24h ɸ
Neisseria meningitidis
Neisseria meningitidis
Penicillin MIC <0.1 μg/mL
Preferred Regimen
Penicillin G Low: 600,000–1.2 million units/day IM; High:≥ 20 million units IV q24h(=12 g)
OR
Ampicillin 0.25–0.5 g po q6h.150–200 mg/kg/day IV
Alternative Regimen
Cefotaxime 1 g q8–12h to 2 g IV q4h
OR
Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine)
OR
Chloramphenicol 0.25–1 g po IV q6h to max. of 4 g/day


Neisseria meningitidis
Penicillin MIC ≥0.1 μg/mL
Preferred Regimen
Cefotaxime 1 g q8–12h to 2 g IV q4h
OR
Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine)
Alternative Regimen
Cefepime 1–2 g IV q12h
OR
Chloramphenicol 0.25–1 g po IV q6h to max. of 4 g/day
OR
FluoroquinoloneΔ
OR
Meropenem 2 g IV q8h
Listeria monocytogenes and Streptococcus agalactiae
Listeria Monocytogenes
Preferred Regimen
Ampicillin 0.25–0.5 g po q6h.150–200 mg/kg/day IV
OR
Penicillin G Low: 600,000–1.2 million units/day IM ;High:≥ 20 million units IV q24h(=12 g)£
Alternative Regimen
Trimethoprim-sulfamethoxazole 5–20 mg/kg/day q6-12h
Streptococcus agalactiae
Preferred Regimen
Ampicillin 0.25–0.5 g po q6h.150–200 mg/kg/day IV
OR
Penicillin G Low: 600,000–1.2 million units/day IM ;High:≥ 20 million units IV q24h(=12 g)£
Alternative Regimen
Cefotaxime 1 g q8–12h to 2 g IV q4h
OR

Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine)
OR
Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h (Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. )

Haemophilus influenzae
Haemophilus influenzae
β-lactamase negative
Preferred Regimen
Ampicillin 0.25–0.5 g po q6h.150–200 mg/kg/day IV
Alternative Regimen
Cefotaxime 1 g q8–12h to 2 g IV q4h
OR
Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine)
OR
Cefepime 1–2 g IV q12h
OR
Chloramphenicol 0.25–1 g po IV q6h to max. of 4 g/day
OR
Aztreonam 1 g IV q8h–2 g IV q6h
OR
FluoroquinoloneΔ
β-lactamase negative, ampicillin resistant
Preferred Regimen
Meropenem 2 g IV q8h
Alternative Regimen
FluoroquinoloneΔ
Haemophilus influenzae
β-lactamase positive
Preferred Regimen
Cefotaxime 1 g q8–12h to 2 g IV q4h
OR
Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine)
Alternative Regimen
Cefepime 1–2 g IV q12h
OR
Chloramphenicol 0.25–1 g po IV q6h to max. of 4 g/day
OR
Aztreonam 1 g q8h–2 g IV q6h
OR
FluoroquinoloneΔ
Staphylococcus aureus
Staphylococcus aureus
Meticillin sensitive
Preferred Regimen
Nafcillin 1–2 g IV/IM q4h
OR
Oxacillin 1–2 g IV/IM q4h
Alternative Regimen
Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h (Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. )
OR
linezolid 600 mg IV/PO q12h
OR
Daptomycin 6 mg/kg IV q24h
Staphylococcus aureus
Meticillin resistant
Preferred Regimen
Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h (Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. )
Alternative Regimen
Trimethoprim-sulfamethoxazole 5–20 mg/kg/day q6-12h
OR
linezolid 600 mg IV/PO q12h
OR
Daptomycin 6 mg/kg IV q24h


Staphylococcus epidermidis and Acinetobacter baumanniiΩ
Staphylococcus epidermidis
Preferred Regimen
Vancomycin give loading dose of 25-30 mg/kg IV then 15-20 mg/kg IV q8-12h (Target trough level is 15-20 µg/mL. For individual doses over 1 gm, infuse over 1.5-2 hrs. )
Alternative Regimen
Linezolid 600 mg IV/PO q12h




Acinetobacter baumannii
Preferred Regimen
Meropenem 2 g IV q8h
Alternative Regimen
Colistin
in US:2.5-5 mg/kg/day q6-12h( 6.7-13.3 mg/kg/day of colistimethate sodium (CMS),max 800 mg/day);
Elsewhere: ≤60 kg, 50,000-75,000 IU/kg/day IV q8h (=4-6 mg/kg per day of CMS). >60 kg, 1-2 mill IU IV q8h (= 80-160 mg IV tid).

OR
Polymyxin B 15,000–25,000 units/kg/day q12hǂ
Enterobacteriaceae and Pseudomonas aeruginosa
EnterobacteriaceaeΩ
Preferred Regimen
Cefotaxime 1 g q8–12h to 2 g IV q4h
OR
Ceftriaxone 1 g IV qd (2 g IV q12h for Purulent meningitis also IM in 1% lidocaine)
Alternative Regimen
Aztreonam 1 g q8h–2 g IV q6h
OR
FluoroquinoloneΔ
OR
Trimethoprim-sulfamethoxazole 5–20 mg/kg/day q6-12h
OR
Meropenem 2 g IV q8h
OR
Ampicillin 150–200 mg/kg/day IV
Pseudomonas aeruginosa
Preferred Regimen
Ceftazidime 1–2 g IV/IM q8–12h
OR
Cefepime 1–2 g IV q12h£
Alternative Regimen
Aztreonam 1 g q8h–2 g IV q6h
OR
Meropenem 2 g IV q8h
OR
Ciprofloxacin 500-750 mg po bid£





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

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