Meningitis medical therapy: Difference between revisions

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Latest revision as of 22:42, 29 July 2020

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. Empiric antimicrobial therapy must be administered after obtaining blood and/or cerebrospinal fluid (CSF) cultures in cases of suspected meningitis. Once a bacterial etiology has been identified on a CSF Gram stain, treatment regimen should be individualized accordingly. Neither neuroimaging (such as CT scan and MRI) nor lumbar puncture should delay the administration of antimicrobial therapy. For neonates (age < 1 month), empirical antimicrobial therapy generally includes Ampicillin 12 g/day IV q4h AND (Cefotaxime 8–12 g/day q4–6h OR Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h). For children older than 1 month and adults < 50 years, the preferred regimen is usually Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h). For adults ≥ 50 years of age, Ampicillin 12g/day IV q4h is added to the usual adult regimen. The duration of therapy is variable depending on the causative pathogen, but generally the duration is between 1-3 weeks. Adjunctive Dexamethasone at a dose of 0.15 mg/kg q6h for 2—4 days may be effective when administered early (0-20 minutes prior to administration of antimicrobial therapy) among pediatric patients with H. influenzae meningitis and among adults with S. pneumoniae meningitis.

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.
Adjunctive use of dexamethasone for bacterial meningitis in selected groups may be 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 either if the CSF Gram stain demonstrates 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 administered to patients who have already received animicrobial therapy because it is unlikely to improve clinical outcome.^[6]

Antimicrobial Regimen

Bacterial meningitis^[18]

1. Empiric antimicrobial therapy based on specific predisposing factors

1.1 Age

1.1.1 Age < 1 month

Common causative pathogens: Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella species
Preferred regimen: Ampicillin 12 g/day IV q4h AND (Cefotaxime 8–12 g/day q4–6h OR Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h)

1.1.2 Age 1–23 months

Common causative pathogens: Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli
Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)

1.1.3 Age 2–50 years

Common causative pathogens: N . meningitidis, S. pneumoniae
Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)

1.1.4 Age > 50 years

Common causative pathogens: S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic Gram-negative bacilli
Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Ampicillin 12 g/day IV q4h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)

1.2 Head trauma

1.2.1 Basilar skull fracture

Common causative pathogens: S. pneumoniae, H. influenzae, group A β-hemolytic streptococci
Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)

1.2.2 Penetrating trauma

Common causative pathogens: Staphylococcus aureus, coagulase-negative staphylococci (especially Staphylococcus epidermidis), aerobic Gram-negative bacilli (including Pseudomonas aeruginosa)
Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h)

1.3 Postneurosurgery

Common causative pathogens: Aerobic Gram-negative bacilli (including P. aeruginosa), S. aureus, coagulase-negative staphylococci (especially S. epidermidis)
Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h)

1.4 CSF shunt

Common causative pathogens: Coagulase-negative staphylococci (especially S. epidermidis), S. aureus, aerobic Gram-negative bacilli (including P. aeruginosa), Propionibacterium acnes
Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h)

2. CSF Gram stain-directed antimicrobial therapy

2.1 Gram positive, lancet-shaped diplococci suggestive of Streptococcus pneumoniae

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
Alternative regimen: Meropenem 6 g/day IV q8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h

2.2 Gram negative diplococci suggestive of Neisseria meningitidis

Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
Alternative regimen: Penicillin G 24 MU/day IV q4h OR Ampicillin 12 g/day IV q4h OR Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Aztreonam 6–8 g/day IV q6–8h

2.3 Gram positive, short bacilli suggestive of Listeria monocytogenes

Preferred regimen: (Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h) ± (Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h)
Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Meropenem 6 g/day IV q8h

2.4 Gram positive cocci in short chains suggestive of Streptococcus agalactiae

Preferred regimen: (Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h) ± (Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h)
Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h

2.5 Gram negative coccobacilli suggestive of Haemophilus influenzae

Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
Alternative regimen: Chloramphenicol 4–6 g/day IV q6h OR Cefepime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h

2.6 Gram negative bacilli suggestive of Escherichia coli

Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
Alternative regimen: Cefepime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h OR Aztreonam 6–8 g/day IV q6–8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h

3. Pathogen-directed antimicrobial therapy

3.1 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

3.2 Borrelia burgdorferi^[19]

Preferred regimen: Ceftriaxone 2 g IV q24h for 10—28 days
Alternative regimen: Cefotaxime 2 g IV q8h for 10—28 days OR Penicillin G 3—4 MU IV q4h for 10—28 days OR Doxycycline 100—200 mg PO q12h for 10—28 days

3.3 Enterococcus species

3.3.1 Ampicillin susceptible

Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h

3.3.2 Ampicillin resistant

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h

3.3.3 Ampicillin and vancomycin resistant

Preferred regimen: Linezolid 600 mg IV q12h

3.4 Escherichia coli and other Enterobacteriaceae

Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Meropenem 6 g/day IV q8h OR Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Ampicillin 12 g/day IV q4h

3.5 Haemophilus influenzae

3.5.1 β-Lactamase negative

Preferred regimen: Ampicillin 12 g/day IV q4h
Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h OR Cefepime 6 g/day IV q8h OR Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h

3.5.2 β-Lactamase positive

Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
Alternative regimen: Cefepime 6 g/day IV q8h OR Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h

3.6 Listeria monocytogenes

Preferred regimen: Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h
Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Meropenem 6 g/day IV q8h

3.7 Mycobacterium tuberculosis

3.7.1 First-line therapy (dosing information: [5][6][7])

3.7.2 Second-line therapy (dosing information: [8][9][10])

3.7.3 Tuberculous meningitis caused by susceptible Mycobacterium tuberculosis^[20]^[21]^[22]^[23]

3.7.3.1 Intensive phase (adult)

Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 2 months AND Rifampin 10 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months

3.7.3.2 Continuation phase (adult)

Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10 mg/kg (max: 600 mg) for 7–10 months

3.7.3.3 Intensive phase (pediatric)

Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 2 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months

3.7.3.3 Continuation phase (pediatric)

Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 7–10 months
Note (1): World Health Organization guidelines recommend that Ethambutol should be replaced by Streptomycin in tuberculous meningitis.^[24] Streptomycin is contraindicated in pregnancy.
Note (2): A 9– to 12–month course of treatment is recommended for tuberculous meningitis.^[25]^[26]

Note (3): Adjuvant Dexamethasone 0.3–0.4 mg/kg/day (max: 24 mg) is recommended unless drug resistance is suspected.^[27]^[28]

Note (4): Liaise with microbiology laboratory about genotype testing for drug resistance if there is high risk for MDR-TB.^[29]

3.7.4 Tuberculous meningitis caused by Mycobacterium tuberculosis resistant to isoniazid or rifampin

3.7.4.1 Isoniazid monoresistance^[30]

Substitute Fluoroquinolones for Isoniazid in intensive phase regimen.
Continue treatment with Rifampin, Pyrazinamide, and Fluoroquinolone for 12 months.

3.7.4.2 Rifampin monoresistance^[31]

Substitute Fluoroquinolones for Rifampin in intensive phase regimen.
Continue treatment with Isoniazid, Pyrazinamide, and Fluoroquinolone for 18 months.

3.7.4.3 MDR-TB (resistant to Isoniazid and Rifampin)^[32]

MDR tuberculosis therapy should be considered if there is a history of prior tuberculosis treatment, contact with a patient with MDR tuberculosis, or a poor clinical response to first-line TB therapy within 2 weeks despite a firm diagnosis and an adequate adherence to treatment.
Second-line agents such as Aminoglycosides penetrate the BBB only in the presence of inflamed meninges, and Fluoroquinolones, while able to penetrate into the CNS, have lower CSF levels than in the serum or brain parenchyma.
Consult infectious disease specialist.

3.7.4.4 XDR-TB (resistant to Isoniazid, Rifampin, Fluoroquinolones, and either Capreomycin, Kanamycin, or Amikacin)^[33]

Consider Ethionamide or Cycloserine to build the treatment regimen.
Consult infectious disease specialist.

3.8 Neisseria gonorrheoae^[34]^[35]

Preferred regimen: Ceftriaxone 1–2 g IV q12h for 10–14 days

3.9 Neisseria meningitidis

3.9.1 Penicillin MIC < 0.1 μg/mL

Preferred regimen: Penicillin G 24 MU/day IV q4h OR Ampicillin 12 g/day IV q4h
Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h OR Chloramphenicol 4–6 g/day IV q6h

3.9.2 Penicillin MIC 0.1–1.0 μg/mL

Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
Alternative regimen: Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Meropenem 6 g/day IV q8h

3.10 Pseudomonas aeruginosa

Preferred regimen: Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h
Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR Ciprofloxacin 800–1200 mg IV q8–12h OR Meropenem 6 g/day IV q8h

3.11 Staphylococcus aureus

3.11.1 Methicillin susceptible (MSSA)

Preferred regimen: Nafcillin 9–12 g/day IV q4h OR Oxacillin 9–12 g/day IV q4h
Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h OR Meropenem 6 g/day IV q8h

3.11.2 Methicillin resistant (MRSA)

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Linezolid 600 mg IV q12h
Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin in adult patients.

3.12 Staphylococcus epidermidis

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
Alternative regimen: Linezolid 600 mg IV q12h

3.13 Streptococcus agalactiae

Preferred regimen: Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h
Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h

3.14 Streptococcus pneumoniae

3.14.1 Penicillin MIC < 0.1 μg/mL

Preferred regimen: Penicillin G 24 MU/day IV q4h OR Ampicillin 12 g/day IV q4h
Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h OR Chloramphenicol 4–6 g/day IV q6h

3.14.2 Penicillin MIC 0.1–1.0 μg/mL

Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
Alternative regimen: Cefepime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h

3.14.3 Penicillin MIC ≥ 2.0 μg/mL

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
Alternative regimen: Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h

3.14.4 Cefotaxime or ceftriaxone MIC ≥ 1.0 μg/mL

Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
Alternative regimen: Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h

3.15 Treponema pallidum (neurosyphilis)^[36]

Preferred regimen: Aqueous crystalline penicillin G 3–4 MU IV q4h or continuously for 10–14 days
Alternative regimen: Procaine penicillin G 2.4 MU IM q24h for 10–14 days AND Probenecid 500 mg PO qid for 10–14 days
Note: Benzathine penicillin G 2.4 MU IM once per week for up to 3 weeks may be considered after completion of above mentioned regimens to provide a comparable total duration of therapy.

3.16 Borrelia burgdorferi (Lyme meningitis)

Preferred regimen (1): Ceftriaxone 2 g IV q24h for 14 days
Preferred regimen (2):Cefotaxime 2 g IV q8h for 14 days
Preferred regimen (3):Penicillin G 18–24 MU/day q4h for 14 days
Alternative regimen: Doxycycline 100–200 mg BID for 14 days
Pediatric regimen: Ceftriaxone 50–75 mg/kg/day IV q24h, max 2 g/day OR Cefotaxime 150–200 mg/kg/day IV q6–8h, max 6 g/day OR Penicillin G 200,000–400,000 U/kg/day IV q4h, max 18–24 MU/day OR Doxycycline (≥ 8 y/o) 4–8 mg/kg/day q12h, max 200 mg/day

4. Pediatric dose:

Amikacin

Neonates age 0–7 days: 15–20 mg/kg/day q12h
Neonates age 8–28 days: 30 mg/kg/day q8h
Infants and children: 20–30 mg/kg/day q8h

Ampicillin

Neonates age 0–7 days: 150 mg/kg/day q8h
Neonates age 8–28 days: 200 mg/kg/day q6–8h
Infants and children: 300 mg/kg/day q6h

Cefepime

Infants and children: 150 mg/kg/day q8h

Cefotaxime

Neonates age 0–7 days: 100–150 mg/kg/day q8–12h
Neonates age 8–28 days: 150–200 mg/kg/day q6–8h
Infants and children: 225–300 mg/kg/day q6–8h

Ceftazidime

Neonates age 0–7 days: 100–150 mg/kg/day q8–12h
Neonates age 8–28 days: 150 mg/kg q8h
Infants and children: 150 mg/kg

Ceftriaxone

Infants and children: 80–100 mg/kg/day q12–24h

Chloramphenicol

Neonates age 0–7 days: 25 mg/kg/day q24h
Neonates age 8–28 days: 50 mg/kg/day q12–24h
Infants and children: 75–100 mg/kg/day q6h

Gentamicin

Neonates age 0–7 days: 5 mg/kg/day q12h
Neonates age 8–28 days: 7.5 mg/kg/day q8h
Infants and children: 7.5 mg/kg/day q8h

Meropenem

Infants and children: 120 mg/kg/day q8h

Nafcillin

Neonates age 0–7 days: 75 mg/kg/day q8–12h
Neonates age 8–28 days: 100–150 mg/kg/day q6–8h
Infants and children: 200 mg/kg/day q6h

Oxacillin

Neonates age 0–7 days: 75 mg/kg/day q8–12h
Neonates age 8–28 days: 150–200 mg/kg/day q6–8h
Infants and children: 200 mg/kg/day q6h

Penicillin G

Neonates age 0–7 days: 0.15 MU/kg/day q8–12h
Neonates age 8–28 days: 0.2 MU/kg/day q6–8h
Infants and children: 0.3 MU/kg/day q4–6h

Rifampin

Neonates age 8–28 days: 10–20 mg/kg/day q12h
Infants and children: 10–20 mg/kg/day q12–24h

Tobramycin

Neonates age 0–7 days: 5 mg/kg/day q12h
Neonates age 8–28 days: 7.5 mg/kg/day q8h
Infants and children: 7.5 mg/kg/day q8h

Trimethoprim-Sulfamethoxazole

Infants and children: 10–20 mg/kg q6–12h

Vancomycin

Neonates age 0–7 days: 20–30 mg/kg/day q8–12h
Neonates age 8–28 days: 30–45 mg/kg/day q6–8h
Infants and children: 60 mg/kg/day q6h

References

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↑ 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)
↑ ^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]
↑ 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
↑ Tunkel, Allan R.; Hartman, Barry J.; Kaplan, Sheldon L.; Kaufman, Bruce A.; Roos, Karen L.; Scheld, W. Michael; Whitley, Richard J. (2004-11-01). "Practice guidelines for the management of bacterial meningitis". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 39 (9): 1267–1284. doi:10.1086/425368. ISSN 1537-6591. PMID 15494903.
↑ Wormser, GP.; Dattwyler, RJ.; Shapiro, ED.; Halperin, JJ.; Steere, AC.; Klempner, MS.; Krause, PJ.; Bakken, JS.; Strle, F. (2006). "The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America". Clin Infect Dis. 43 (9): 1089–134. doi:10.1086/508667. PMID 17029130. Unknown parameter |month= ignored (help)
↑ Blumberg, Henry M.; Burman, William J.; Chaisson, Richard E.; Daley, Charles L.; Etkind, Sue C.; Friedman, Lloyd N.; Fujiwara, Paula; Grzemska, Malgosia; Hopewell, Philip C.; Iseman, Michael D.; Jasmer, Robert M.; Koppaka, Venkatarama; Menzies, Richard I.; O'Brien, Richard J.; Reves, Randall R.; Reichman, Lee B.; Simone, Patricia M.; Starke, Jeffrey R.; Vernon, Andrew A.; American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society (2003-02-15). "American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis". American Journal of Respiratory and Critical Care Medicine. 167 (4): 603–662. doi:10.1164/rccm.167.4.603. ISSN 1073-449X. PMID 12588714.
↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link)
↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786. Retrieved 2015-06-08.
↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786. Retrieved 2015-06-08.
↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
↑ Thwaites, Guy E.; Nguyen, Duc Bang; Nguyen, Huy Dung; Hoang, Thi Quy; Do, Thi Tuong Oanh; Nguyen, Thi Cam Thoa; Nguyen, Quang Hien; Nguyen, Tri Thuc; Nguyen, Ngoc Hai; Nguyen, Thi Ngoc Lan; Nguyen, Ngoc Lan; Nguyen, Hong Duc; Vu, Ngoc Tuan; Cao, Huu Hiep; Tran, Thi Hong Chau; Pham, Phuong Mai; Nguyen, Thi Dung; Stepniewska, Kasia; White, Nicholas J.; Tran, Tinh Hien; Farrar, Jeremy J. (2004-10-21). "Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults". The New England Journal of Medicine. 351 (17): 1741–1751. doi:10.1056/NEJMoa040573. ISSN 1533-4406. PMID 15496623.
↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link)
↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link)
↑ Workowski, Kimberly A.; Berman, Stuart; Centers for Disease Control and Prevention (CDC) (2010–12–17). "Sexually transmitted diseases treatment guidelines, 2010". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 59 (RR–12): 1–110. ISSN 1545-8601. PMID 21160459. Check date values in: |date= (help)
↑ Centers for Disease Control and Prevention (CDC) (2012–08–10). "Update to CDC's Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections". MMWR. Morbidity and mortality weekly report. 61 (31): 590–594. ISSN 1545-861X. PMID 22874837. Check date values in: |date= (help)
↑ Workowski, Kimberly A.; Berman, Stuart; Centers for Disease Control and Prevention (CDC) (2010–12–17). "Sexually transmitted diseases treatment guidelines, 2010". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 59 (RR–12): 1–110. ISSN 1545-8601. PMID 21160459. Check date values in: |date= (help)

Tuberculous meningitis (TB meningitis)

First-line therapy (dosing information: [11][12][13])

Second-line therapy (dosing information: [14][15][16])

Tuberculous meningitis caused by susceptible Mycobacterium tuberculosis^[1]^[2]^[3]^[4]

Intensive phase (adult)

Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 2 months AND Rifampin 10 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months

Continuation phase (adult)

Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10 mg/kg (max: 600 mg) for 7–10 months

Intensive phase (pediatric)

Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 2 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months

Continuation phase (pediatric)

Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 7–10 months

Note (1): World Health Organization guidelines recommend that Ethambutol should be replaced by Streptomycin (contraindicated in pregnancy) in tuberculous meningitis.^[5]

Note (2): A 9– to 12–month course of treatment is recommended for tuberculous meningitis.^[6]^[7]

Note (3): Adjuvant Dexamethasone 0.3–0.4 mg/kg/day (max: 24 mg) is recommended unless drug resistance is suspected.^[8]^[9]

Note (4): Liaise with microbiology laboratory about genotype testing for drug resistance if there is high risk for MDR-TB.^[10]

Tuberculous meningitis caused by Mycobacterium tuberculosis resistant to isoniazid or rifampin

Isoniazid monoresistance^[11]

Substitute fluoroquinolone for isoniazid in intensive phase regimen.
Continue treatment with rifampin, pyrazinamide, and fluoroquinolone for 12 months.

Rifampin monoresistance^[12]

Substitute Fluoroquinolones for Rifampin in intensive phase regimen.
Continue treatment with isoniazid, pyrazinamide, and fluoroquinolone for 18 months.

MDR-TB (resistant to Isoniazid and Rifampin)^[13]

MDR tuberculosis therapy should be considered if there is a history of prior tuberculosis treatment, contact with a patient with MDR tuberculosis, or a poor clinical response to first-line TB therapy within 2 weeks despite a firm diagnosis and an adequate adherence to treatment.
Second-line agents such as Aminoglycosides penetrate the BBB only in the presence of inflamed meninges, and Fluoroquinolones, while able to penetrate into the CNS, have lower CSF levels than in the serum or brain parenchyma.
Consult infectious disease specialist.

XDR-TB (resistant to Isoniazid, Rifampin, Fluoroquinolones, and either Capreomycin, Kanamycin, or Amikacin)^[14]

Consider Ethionamide or Cycloserine to build the treatment regimen.
Consult infectious disease specialist.

References

↑ Blumberg, Henry M.; Burman, William J.; Chaisson, Richard E.; Daley, Charles L.; Etkind, Sue C.; Friedman, Lloyd N.; Fujiwara, Paula; Grzemska, Malgosia; Hopewell, Philip C.; Iseman, Michael D.; Jasmer, Robert M.; Koppaka, Venkatarama; Menzies, Richard I.; O'Brien, Richard J.; Reves, Randall R.; Reichman, Lee B.; Simone, Patricia M.; Starke, Jeffrey R.; Vernon, Andrew A.; American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society (2003-02-15). "American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis". American Journal of Respiratory and Critical Care Medicine. 167 (4): 603–662. doi:10.1164/rccm.167.4.603. ISSN 1073-449X. PMID 12588714.
↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link)
↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786.
↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786.
↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
↑ Thwaites, Guy E.; Nguyen, Duc Bang; Nguyen, Huy Dung; Hoang, Thi Quy; Do, Thi Tuong Oanh; Nguyen, Thi Cam Thoa; Nguyen, Quang Hien; Nguyen, Tri Thuc; Nguyen, Ngoc Hai; Nguyen, Thi Ngoc Lan; Nguyen, Ngoc Lan; Nguyen, Hong Duc; Vu, Ngoc Tuan; Cao, Huu Hiep; Tran, Thi Hong Chau; Pham, Phuong Mai; Nguyen, Thi Dung; Stepniewska, Kasia; White, Nicholas J.; Tran, Tinh Hien; Farrar, Jeremy J. (2004-10-21). "Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults". The New England Journal of Medicine. 351 (17): 1741–1751. doi:10.1056/NEJMoa040573. ISSN 1533-4406. PMID 15496623.
↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link)
↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link)

Meningitis, parasitic

1. Protozoal meningitis

1.1 Naegleria fowleri (primary amebic meningoencephalitis)^[1]^[2]

Preferred regimen: (Amphotericin B 1.5 mg/kg/day IV q12h for 3 days, followed by Amphotericin B 1 mg/kg/day IV q24h for 11 days) AND (Amphotericin B 1.5 mg/kg/day intrathecal q24h for 2 days, followed by Amphotericin B 1 mg/kg/day intrathecal qod for 8 days) AND Azithromycin 10 mg/kg/day IV/PO q24h for 28 days AND Fluconazole 10 mg/kg/day IV/PO q24h for 28 days AND Rifampin 10 mg/kg/day IV/PO q24h for 28 days AND Miltefosine 50 mg PO bid–tid for 28 days AND Dexamethasone 0.15 mg/kg IV q6h for 4 days

1.2 Toxoplasma gondii^[3]

Preferred regimen: Sulfadiazine 4–6 g/day q6h AND Pyrimethamine 25–100 mg/day qd
Alternative regimen (1): Pyrimethamine 25–100 mg/day qd AND Clindamycin 2400–4800 mg/day IV q6h
Alternative regimen (2): Pyrimethamine 25–100 mg/day qd AND (Azithromycin 1200–1500 mg/day IV q24h OR Atovaquone 750 mg IV q6h OR Dapsone 100 mg PO q24h)
Alternative regimen (3): TMP-SMZ 10–20 mg/kg/day q6–12h

2. Helminthic meningitis

2.1 Angiostrongylus cantonensis^[4]^[5]

Preferred regimen: Albendazole 15–20 mg/kg/day PO qd–bid for 10–20 days AND Dexamethasone 10–20 mg PO qd for 10–20 days
Alternative regimen: Mebendazole 100 mg PO bid for 10–20 days AND Dexamethasone 10–20 mg PO qd for 10–20 days

2.2 Baylisascaris procyonis^[6]^[7]

Preferred regimen: Albendazole 25–50 mg/kg PO qd or 400 mg PO bid for 10 days AND Dexamethasone 10–20 mg PO qd for 10 days
Alternative regimen: Thiabendazole 50 mg/kg/day PO bid for 10 days AND Dexamethasone 10–20 mg PO qd for 10 days

2.3 Gnathostoma spinigerum^[8]^[9]

Preferred regimen: Albendazole 400 mg PO bid for 3 weeks AND Dexamethasone 10–20 mg PO qd for 3 weeks
Alternative regimen: Ivermectin 0.2 mg/kg PO qd for 2 days AND Dexamethasone 10–20 mg PO qd for 3 weeks

References

↑ Linam, W. Matthew; Ahmed, Mubbasheer; Cope, Jennifer R.; Chu, Craig; Visvesvara, Govinda S.; da Silva, Alexandre J.; Qvarnstrom, Yvonne; Green, Jerril (2015-03). "Successful treatment of an adolescent with Naegleria fowleri primary amebic meningoencephalitis". Pediatrics. 135 (3): –744-748. doi:10.1542/peds.2014-2292. ISSN 1098-4275. PMID 25667249. Check date values in: |date= (help)
↑ Vargas-Zepeda, Jesús; Gómez-Alcalá, Alejandro V.; Vásquez-Morales, José Alfonso; Licea-Amaya, Leonardo; De Jonckheere, Johan F.; Lares-Villa, Fernando (2005-02). "Successful treatment of Naegleria fowleri meningoencephalitis by using intravenous amphotericin B, fluconazole and rifampicin". Archives of Medical Research. 36 (1): 83–86. ISSN 0188-4409. PMID 15900627. Check date values in: |date= (help)
↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013.
↑ Wang, Qiao-Ping; Lai, De-Hua; Zhu, Xing-Quan; Chen, Xiao-Guang; Lun, Zhao-Rong (2008-10). "Human angiostrongyliasis". The Lancet. Infectious Diseases. 8 (10): 621–630. doi:10.1016/S1473-3099(08)70229-9. ISSN 1473-3099. PMID 18922484. Check date values in: |date= (help)
↑ Ramirez-Avila, Lynn; Slome, Sally; Schuster, Frederick L.; Gavali, Shilpa; Schantz, Peter M.; Sejvar, James; Glaser, Carol A. (2009-02-01). "Eosinophilic meningitis due to Angiostrongylus and Gnathostoma species". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 48 (3): 322–327. doi:10.1086/595852. ISSN 1537-6591. PMID 19123863.
↑ Gavin, Patrick J.; Kazacos, Kevin R.; Shulman, Stanford T. (2005-10). "Baylisascariasis". Clinical Microbiology Reviews. 18 (4): 703–718. doi:10.1128/CMR.18.4.703-718.2005. ISSN 0893-8512. PMC 1265913. PMID 16223954. Check date values in: |date= (help)CS1 maint: PMC format (link)
↑ Murray, William J.; Kazacos, Kevin R. (2004-11-15). "Raccoon roundworm encephalitis". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 39 (10): 1484–1492. doi:10.1086/425364. ISSN 1537-6591. PMID 15546085.
↑ Herman, Joanna S.; Chiodini, Peter L. (2009-07). "Gnathostomiasis, another emerging imported disease". Clinical Microbiology Reviews. 22 (3): 484–492. doi:10.1128/CMR.00003-09. ISSN 1098-6618. PMC 2708391. PMID 19597010. Check date values in: |date= (help)CS1 maint: PMC format (link)
↑ Ramirez-Avila, Lynn; Slome, Sally; Schuster, Frederick L.; Gavali, Shilpa; Schantz, Peter M.; Sejvar, James; Glaser, Carol A. (2009-02-01). "Eosinophilic meningitis due to Angiostrongylus and Gnathostoma species". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 48 (3): 322–327. doi:10.1086/595852. ISSN 1537-6591. PMID 19123863.

Fungal meningitis

1. Blastomyces dermatitidis^[1]

Preferred regimen: Liposomal Amphotericin B 5 mg/kg/day IV for 4–6 weeks, followed by Fluconazole 800 mg PO qd OR Itraconazole 200 mg PO bid–tid OR Voriconazole 200–400 mg PO bid for ≥12 months until CSF abnl resolves

2. Candida spp.^[2]

Preferred regimen: Liposomal Amphotericin B 3–5 mg/kg/day IV ± Flucytosine 25 mg/kg PO qid for several weeks, followed by Fluconazole 400–800 mg (6–12 mg/kg) PO qd until CSF abnl resolves
Alternative regimen: Fluconazole 400–800 mg PO qd (6–12 mg/kg IV q24h) OR Voriconazole 400 mg PO bid for 2 doses, followed by 200 mg PO bid OR Voriconazole 6 mg/kg IV q12h for 2 doses, followed by 3 mg/kg IV q12h

Note: Removal of intraventricular devices is recommended.

3. Coccidioides immitis^[3]

Preferred regimen: Fluconazole 400 mg PO qd
Alternative regimen: Itraconazole 200 mg PO bid–tid

4. Cryptococcus neoformans^[4]

4.1 Non–HIV/AIDS hosts, non–transplant recipients

Induction therapy: (Amphotericin B 0.7–1.0 mg/kg IV q24h for 4–6 weeks OR Liposomal Amphotericin B 3–4 mg/kg IV q24h for 4–6 weeks OR Amphotericin B lipid complex 5 mg/kg IV q24h for 4–6 weeks) AND Flucytosine 25 mg/kg PO q6h for 4–6 weeks
Consolidation therapy: Fluconazole 400–800 mg PO q24h for 8 weeks
Maintenance therapy: Fluconazole 200 mg PO q24h for 6–12 months

4.2 HIV/AIDS hosts

Induction therapy (1): (Amphotericin B 0.7–1.0 mg/kg IV q24h for ≥ 2 weeks OR Liposomal Amphotericin B 3–4 mg/kg IV q24h for ≥ 2 weeks OR Amphotericin B lipid complex 5 mg/kg IV q24h for ≥ 2 weeks) AND Flucytosine 25 mg/kg PO q6h for ≥ 2 weeks
Induction therapy (2): Amphotericin B 0.7–1.0 mg/kg IV q24h for 4–6 weeks OR Liposomal Amphotericin B 3–4 mg/kg IV q24h for 4–6 weeks OR Amphotericin B lipid complex 5 mg/kg IV q24h for 4–6 weeks
Induction therapy (3): Amphotericin B 0.7–1.0 mg/kg IV q24h for 2 weeks AND Fluconazole 800 mg PO q24h for 2 weeks
Induction therapy (4): Fluconazole 1200 mg PO q24h for 6 weeks AND Flucytosine 100 mg/kg PO q24h for 6 weeks
Induction therapy (5): Fluconazole 800–2000 mg PO q24h for 10–12 weeks
Induction therapy (6): Itraconazole 200 mg PO q12h for 10–12 weeks
Consolidation therapy: Fluconazole 400 mg PO q24h for 8 weeks
Maintenance therapy: Fluconazole 200 mg PO q24h for ≥ 1 year OR Itraconazole 400 mg PO q24h for ≥ 1 year OR Amphotericin B 1.0 mg/kg/week IV for ≥ 1 year

4.3 Transplant recipients

Induction therapy (1): (Liposomal Amphotericin B 3–4 mg/kg IV q24h for ≥ 2 weeks OR Amphotericin B lipid complex 5 mg/kg IV q24h for ≥ 2 weeks) AND Flucytosine 25 mg/kg PO q6h for ≥ 2 weeks
Induction therapy (2): Liposomal Amphotericin B 3–4 mg/kg IV q24h for 4–6 weeks OR Amphotericin B lipid complex 5 mg/kg IV q24h for 4–6 weeks
Consolidation therapy: Fluconazole 400–800 mg PO q24h for 8 weeks
Maintenance therapy: Fluconazole 200–400 mg PO q24h for 6–12 months

5. Histoplasma capsulatum^[5]

Preferred regimen: Liposomal Amphotericin B 5 mg/kg IV q24h for 4–6 weeks, followed by Itraconazole 200 mg PO bid–tid for ≥ 12 months

Viral meningitis^[6]

1. Chronic enterovirus meningoencephalitis

Preferred regimen: supportive care ± Pleconaril (investigational)

2. HSV-2 meningitis

Preferred regimen: supportive care AND Acyclovir 10 mg/kg IV q8h for 10–14 days, followed by Valacyclovir 1 g PO tid

3. Mollaret's meningitis

Preferred regimen: supportive care AND Acyclovir 400 mg bid–tid OR Famciclovir 250 mg PO bid OR Valacyclovir 500 mg PO qd

4. VZV meningitis

Preferred regimen: supportive care AND Acyclovir 10 mg/kg IV q8h for 10–14 days, followed by Valacyclovir 1 g PO tid

References

↑ Chapman, Stanley W.; Dismukes, William E.; Proia, Laurie A.; Bradsher, Robert W.; Pappas, Peter G.; Threlkeld, Michael G.; Kauffman, Carol A.; Infectious Diseases Society of America (2008-06-15). "Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 46 (12): 1801–1812. doi:10.1086/588300. ISSN 1537-6591. PMID 18462107.
↑ Pappas, Peter G.; Kauffman, Carol A.; Andes, David; Benjamin, Daniel K.; Calandra, Thierry F.; Edwards, John E.; Filler, Scott G.; Fisher, John F.; Kullberg, Bart-Jan; Ostrosky-Zeichner, Luis; Reboli, Annette C.; Rex, John H.; Walsh, Thomas J.; Sobel, Jack D.; Infectious Diseases Society of America (2009-03-01). "Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 48 (5): 503–535. doi:10.1086/596757. ISSN 1537-6591. PMID 19191635.
↑ Galgiani, John N.; Ampel, Neil M.; Blair, Janis E.; Catanzaro, Antonino; Johnson, Royce H.; Stevens, David A.; Williams, Paul L.; Infectious Diseases Society of America (2005-11-01). "Coccidioidomycosis". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 41 (9): 1217–1223. doi:10.1086/496991. ISSN 1537-6591. PMID 16206093.
↑ Perfect, John R.; Dismukes, William E.; Dromer, Francoise; Goldman, David L.; Graybill, John R.; Hamill, Richard J.; Harrison, Thomas S.; Larsen, Robert A.; Lortholary, Olivier; Nguyen, Minh-Hong; Pappas, Peter G.; Powderly, William G.; Singh, Nina; Sobel, Jack D.; Sorrell, Tania C. (2010-02-01). "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 50 (3): 291–322. doi:10.1086/649858. ISSN 1537-6591. PMID 20047480.
↑ Wheat, L. Joseph; Freifeld, Alison G.; Kleiman, Martin B.; Baddley, John W.; McKinsey, David S.; Loyd, James E.; Kauffman, Carol A.; Infectious Diseases Society of America (2007-10-01). "Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 45 (7): 807–825. doi:10.1086/521259. ISSN 1537-6591. PMID 17806045.
↑ Bartlett, John (2012). Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases. Burlington, MA: Jones and Bartlett Learning. ISBN 978-1449625580.

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+__NOTOC__
 {{Meningitis}}
-{{CMG}}; '''Associate Editor(s)-In-Chief:'''  {{CZ}}
+{{CMG}}; {{AE}} {{CZ}}, {{SS}}
 ==Overview==
+Acute bacterial meningitis is a medical emergency. Empiric antimicrobial therapy must be administered after obtaining blood and/or [[cerebrospinal fluid|cerebrospinal fluid (CSF)]] cultures in cases of suspected meningitis. Once a bacterial etiology has been identified on a [[CSF]] [[Gram stain]], treatment regimen should be individualized accordingly.  Neither neuroimaging (such as [[CT scan]] and [[MRI]]) nor [[lumbar puncture]] should delay the administration of antimicrobial therapy. For neonates (age < 1 month), empirical antimicrobial therapy generally includes [[Ampicillin]] 12 g/day IV q4h {{and}} ([[Cefotaxime]] 8–12 g/day q4–6h {{or}} [[Amikacin]] 15 mg/kg/day IV q8h {{or}} [[Gentamicin]] 5 mg/kg/day IV q8h {{or}} [[Tobramycin]] 5 mg/kg/day IV q8h). For children older than 1 month and adults < 50 years, the preferred regimen is usually [[Vancomycin]] 30–45 mg/kg/day IV q8–12h {{and}} ([[Ceftriaxone]] 4 g IV q12–24h {{or}} [[Cefotaxime]] 8–12 g/day q4–6h). For adults ≥ 50 years of age, [[Ampicillin]] 12g/day IV q4h is added to the usual adult regimen. The duration of therapy is variable depending on the causative pathogen, but generally the duration is between 1-3 weeks. Adjunctive [[Dexamethasone]] at a dose of 0.15 mg/kg q6h for 2—4 days may be effective when administered early (0-20 minutes prior to administration of antimicrobial therapy) among pediatric patients with ''H. influenzae'' meningitis and among adults with ''S. pneumoniae'' meningitis.
-==Bacterial meningitis==
+==Principles of Therapy for Bacterial Meningitis==
-Bacterial meningitis is a [[medical emergency]] and has a high mortality rate if untreated.<ref name=Beckham_2006>{{cite journal |author=Beckham J, Tyler K |title=Initial Management of Acute Bacterial Meningitis in Adults: Summary of IDSA Guidelines |journal=Rev Neurol Dis |volume=3 |issue=2 |pages=57-60 |year=2006 |pmid=16819421}}</ref> All suspected cases, however mild, need emergency medical attention. Empiric antibiotics must be started immediately, even before the results of the [[lumbar puncture]] and [[Cerebrospinal fluid|CSF]] analysis are known. Antibiotics started within 4 hours of lumbar puncture will not significantly affect lab results. Adjuvant treatment with [[corticosteroids]] reduces rates of mortality, severe hearing loss and neurological sequelae.<ref>{{cite journal |author=van de Beek D, de Gans J, McIntyre P, Prasad K |title=Corticosteroids for acute bacterial meningitis |journal=Cochrane database of systematic reviews (Online) |volume= |issue=1 |pages=CD004405 |year=2007 |pmid=17253505 |doi=10.1002/14651858.CD004405.pub2}}</ref>
-{| class = "prettytable" style = "float:right; font-size:85%; margin-left:15px"
+===Factors Determining Antimicrobial Activity===
+* Factors determine the acitivity of antimicrobial agents include [[pharmacodynamics]], [[pharmacokinetics]], penetration into the CSF, and [[bactericidal]] activity within the CSF.<ref name="Andes-1999">{{Cite journal  | last1 = Andes | first1 = DR. | last2 = Craig | first2 = WA. | title = Pharmacokinetics and pharmacodynamics of antibiotics in meningitis. | journal = Infect Dis Clin North Am | volume = 13 | issue = 3 | pages = 595-618 | month = Sep | year = 1999 | doi =  | PMID = 10470557 }}</ref>
+* [[Beta-lactam]]s, [[aminoglycoside]]s, [[glycopeptide]]s, [[linezolid]], and [[daptomycin]] are considered to have poor penetration into the CSF, while [[fluoroquinolone]]s, [[chloramphenicol]], [[aztreonam]], and [[tigecycline]] generally achieve [[MIC|minimum inhibitory concentration (MIC)]] in the CSF at standard dosage.<ref name="Nau-2010">{{Cite journal  | last1 = Nau | first1 = R. | last2 = Sörgel | first2 = F. | last3 = Eiffert | first3 = H. | title = Penetration of drugs through the blood-cerebrospinal fluid/blood-brain barrier for treatment of central nervous system infections. | journal = Clin Microbiol Rev | volume = 23 | issue = 4 | pages = 858-83 | month = Oct | year = 2010 | doi = 10.1128/CMR.00007-10 | PMID = 20930076 }}</ref>
+* [[Aminoglycoside]]s and [[fluoroquinolone]]s express a concentration-dependent manner of bactericidal activity; [[beta-lactam]]s 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 [[penicillin]]s and [[cephalosporin]]s. Toxicity due to dose escalation may limit the usage the [[aminoglycoside]]s, [[glycopeptide]]s, and [[polymyxin]]s, thus [[intrathecal]] or [[intraventricular]] administration might be occasionally required (see table below).
+{| style="border: 2px solid #696969;"
+|+ <SMALL>''Recommended Doses of Antimicrobial Agents via 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: #545454; border: 0px solid #696969; padding: 0 5px; width: 300px; color: #F8F8FF;"| '''Antimicrobial Agent''' || style="background: #545454; border: 0px solid #696969; padding: 0 5px; width: 300px; color: #F8F8FF;" | '''Daily Intraventricular Dose'''
 |-
-! Age group
+| 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'''''
-! Causes
 |-
-| [[Neonate]]s
+| 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'''''
-| Group B Streptococci, ''[[Escherichia coli]]'', ''[[Listeria monocytogenes]]''
 |-
-| Infants
+| 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'''''
-| ''[[Neisseria meningitidis]]'', ''[[Haemophilus influenzae]]'', ''[[Streptococcus pneumoniae]]''
 |-
-| Children
+| 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'''''
-|''N. meningitidis'', ''S. pneumoniae''
+|-
+| 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;'''''[[Colistin]]''''' || 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'''''
+|-
+| 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'''''
 |-
-| Adults
-| ''S. pneumoniae'', ''N. meningitidis'', Mycobacteria, Cryptococci
 |}
-The choice of antibiotic depends on local advice.  In most of the developed world, the most common organisms involved are ''[[Streptococcus pneumoniae]]'' and ''[[Neisseria meningitidis]]'': first line treatment in the UK is a third-generation [[cephalosporin]] (such as [[ceftriaxone]] or [[cefotaxime]]). In those under 3 years of age, over 50 years of age, or immunocompromised, [[ampicillin]] should be added to cover ''[[Listeria monocytogenes]]''.  In the U.S. and other countries with high levels of penicillin resistance, the first line choice of antibiotics is [[vancomycin]] and a [[carbapenem]] (such as [[meropenem]]).  In sub-Saharan Africa, oily [[chloramphenicol]] or [[ceftriaxone]] are often used because only a single dose is needed in most cases.
-Staphylococci and gram-negative bacilli are common infective agents in patients who have just had a neurosurgical procedure. Again, the choice of antibiotic depends on local patterns of infection: [[cefotaxime]] and [[ceftriaxone]] remain good choices in many situations, but [[ceftazidime]] is used when ''[[Pseudomonas aeruginosa]]'' is a problem, and intraventricular [[vancomycin]] is used for those patients with intraventricular shunts because of high rates of [[Staphylococcus|staphylococcal]] infection.  In patients with intracerebral prosthetic material (metal plates, electrodes or implants, etc.) then sometimes [[chloramphenicol]] is the only antibiotic that will adequately cover infection by ''[[Staphylococcus aureus]]'' (cephalosporins and carbapenems are inadequate under these circumstances).
+==Duration of Antimicrobial Therapy==
-Once the results of the CSF analysis are known along with the Gram-stain and culture, empiric therapy may be switched to therapy targeted to the specific causative organism and its sensitivities.
+* The duration of therapy in patients with bacterial meningitis has not been well-supported by evidence-based data.
-*''[[Neisseria meningitidis]]'' (Meningococcus) can usually be treated with a 7-day course of IV antibiotics:
-**Penicillin-sensitive -- [[penicillin]] G or [[ampicillin]]
-**Penicillin-resistant -- [[ceftriaxone]] or [[cefotaxime]]
-**Prophylaxis for close contacts (contact with oral secretions) -- [[rifampin]] 600 mg bid for 2 days ''(adults)'' or 10 mg/kg bid ''(children)''. Rifampin is not recommended in pregnancy and as such, these patients should be treated with single doses of [[ciprofloxacin]], [[azithromycin]], or [[ceftriaxone]]
-*''[[Streptococcus pneumoniae]]'' (Pneumococcus) can usually be treated with a 2-week course of IV antibiotics:
-**Penicillin-sensitive -- [[penicillin]] G
-**Penicillin-intermediate -- [[ceftriaxone]] or [[cefotaxime]]
-**Penicillin-resistant -- [[ceftriaxone]] or [[cefotaxime]] + [[vancomycin]]
-*''[[Listeria monocytogenes]]'' is treated with a 3-week course of IV [[ampicillin]] + [[gentamicin]].
-*Gram negative bacilli -- [[ceftriaxone]] or [[cefotaxime]]
-*''[[Pseudomonas aeruginosa]]'' -- [[ceftazidime]]''
-*''[[Staphylococcus aureus]]''
-**Methicillin-sensitive -- [[nafcillin]]
-**Methicillin-resistant -- [[vancomycin]]
-*''[[Streptococcus agalactiae]]'' -- [[penicillin]] G or [[ampicillin]]
-*''[[Haemophilus influenzae]]'' -- [[ceftriaxone]] or [[cefotaxime]]
-==Viral meningitis==
+* 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.
-Unlike bacteria, viruses cannot be killed by antibiotics. Patients with very mild viral meningitis may only have to spend a few hours in a hospital, while those who have a more serious infection may be hospitalised for many more days for supportive care. Patients with mild cases, which often cause only flu-like symptoms, may be treated with fluids, bed rest (preferably in a quiet, dark room), and analgesics for pain and fever. Serious cases, especially in the case of young children or neonates, may require the use of antiviral drugs, such as [[acyclovir]]. The physician may also prescribe [[anticonvulsant]]s such as [[phenytoin]] to prevent [[seizure]]s and [[corticosteroid]]s to reduce brain inflammation. If inflammation is severe, pain medicine and sedatives may be prescribed to make the patient more comfortable.
-==Fungal meningitis==
+* Maximum [[parenteral]] dosage should be maintained throughout the recommended duration of therapy to ensure adequate bactericidal concentrations are attained since antimicrobial entry attenuates as [[meninges|meningeal]] inflammation subsides, especially when [[dexamethasone]] is co-administered.
-This form of meningitis is rare in otherwise healthy people, but is a higher risk in those who have [[AIDS]], other forms of [[immunodeficiency]] (an immune system that does not respond adequately to infections) and [[immunosuppression]] (immune system malfunction as a result of medical treatment). In AIDS, ''[[Cryptococcus neoformans]]'' is the most common cause of fungal meningitis; it requires Indian ink staining of the CSF sample for identification of this capsulated yeast. Fungal meningitis is treated with long courses of highly dosed [[Antifungal drug|antifungals]].<ref>{{cite journal |author=Gottfredsson M, Perfect JR |title=Fungal meningitis |journal=Seminars in neurology |volume=20 |issue=3 |pages=307-22 |year=2000 |pmid=11051295 |doi=}}</ref>
+{| style="border: 2px solid #696969;"
+|+ <SMALL><SMALL>''Recommended Duration of Antimicrobial Therapy Based on Isolated Pathogen.''<ref name="pmid15494903">Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15494903 Practice guidelines for the management of bacterial meningitis.] ''Clin Infect Dis'' 39 (9):1267-84. [http://dx.doi.org/10.1086/425368 DOI:10.1086/425368] PMID: [http://pubmed.gov/1549490315494903]</ref></SMALL></SMALL>
+| style="background: #545454; border: 0px solid #696969; padding: 0 5px; width: 300px; color: #F8F8FF;"| '''Microorganism''' || style="background: #545454; border: 0px solid #696969; padding: 0 5px; width: 300px; color: #F8F8FF;" | '''Duration of Therapy'''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Neisseria meningitidis]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''7 days'''''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Haemophilus influenzae]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''7 days'''''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Streptococcus pneumoniae]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''10—14 days'''''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Streptococcus agalactiae]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''14—21 days'''''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Gram-negative bacteria|Aerobic Gram-negative bacilli]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left |  '''''21 days'''''
+|-
+| style="font-size: 90%; padding: 0 5px; background: #F5F5F5" align=left |&nbsp;▸&nbsp;'''''[[Listeria monocytogenes]]''''' || style="font-size: 90%; padding: 0 5px; background: #DCDCDC" align=left | '''''≥21 days'''''
+|-
+|}
+==Adjunctive Dexamethasone Therapy==
+* Evidences for beneficial effects of [[dexamethasone]] are variable.
+*Adjunctive use of dexamethasone for bacterial meningitis in selected groups may be associated with an improved survival or prognosis.<ref name="Lebel-1988">{{Cite journal  | last1 = Lebel | first1 = MH. | last2 = Freij | first2 = BJ. | last3 = Syrogiannopoulos | first3 = GA. | last4 = Chrane | first4 = DF. | last5 = Hoyt | first5 = MJ. | last6 = Stewart | first6 = SM. | last7 = Kennard | first7 = BD. | last8 = Olsen | first8 = KD. | last9 = McCracken | first9 = GH. | title = Dexamethasone therapy for bacterial meningitis. Results of two double-blind, placebo-controlled trials. | journal = N Engl J Med | volume = 319 | issue = 15 | pages = 964-71 | month = Oct | year = 1988 | doi = 10.1056/NEJM198810133191502 | PMID = 3047581 }}</ref><ref name="Odio-1991">{{Cite journal  | last1 = Odio | first1 = CM. | last2 = Faingezicht | first2 = I. | last3 = Paris | first3 = M. | last4 = Nassar | first4 = M. | last5 = Baltodano | first5 = A. | last6 = Rogers | first6 = J. | last7 = Sáez-Llorens | first7 = X. | last8 = Olsen | first8 = KD. | last9 = McCracken | first9 = GH. | title = The beneficial effects of early dexamethasone administration in infants and children with bacterial meningitis. | journal = N Engl J Med | volume = 324 | issue = 22 | pages = 1525-31 | month = May | year = 1991 | doi = 10.1056/NEJM199105303242201 | PMID = 2027357 }}</ref><ref name="Thwaites-2004">{{Cite journal  | last1 = Thwaites | first1 = GE. | last2 = Nguyen | first2 = DB. | last3 = Nguyen | first3 = HD. | last4 = Hoang | first4 = TQ. 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childhood bacterial meningitis is little relieved by dexamethasone or glycerol. | journal = Pediatrics | volume = 125 | issue = 1 | pages = e1-8 | month = Jan | year = 2010 | doi = 10.1542/peds.2009-0395 | PMID = 20008417 }}</ref><ref name="Nguyen-2007">{{Cite journal  | last1 = Nguyen | first1 = TH. | last2 = Tran | first2 = TH. | last3 = Thwaites | first3 = G. | last4 = Ly | first4 = VC. | last5 = Dinh | first5 = XS. | last6 = Ho Dang | first6 = TN. | last7 = Dang | first7 = QT. | last8 = Nguyen | first8 = DP. | last9 = Nguyen | first9 = HP. | title = Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. | journal = N Engl J Med | volume = 357 | issue = 24 | pages = 2431-40 | month = Dec | year = 2007 | doi = 10.1056/NEJMoa070852 | PMID = 18077808 }}</ref><ref name="Molyneux-2002">{{Cite journal  | last1 = Molyneux | first1 = EM. | last2 = Walsh | first2 = AL. | last3 = Forsyth | first3 = H. | last4 = Tembo | first4 = M. | last5 = Mwenechanya | first5 = J. | 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+* '''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.<ref name="pmid15494903">Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15494903 Practice guidelines for the management of bacterial meningitis.] ''Clin Infect Dis'' 39 (9):1267-84. [http://dx.doi.org/10.1086/425368 DOI:10.1086/425368] PMID: [http://pubmed.gov/15494903 15494903]</ref>
+* '''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 either if the [[CSF]] [[Gram stain]] demonstrates [[Gram-positive]] [[diplococci]] or if blood or CSF cultures are positive for ''[[Streptococcus pneumoniae|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.<ref name="pmid15494903">Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15494903 Practice guidelines for the management of bacterial meningitis.] ''Clin Infect Dis'' 39 (9):1267-84. [http://dx.doi.org/10.1086/425368 DOI:10.1086/425368] PMID: [http://pubmed.gov/15494903 15494903]</ref><ref name="pmid16394301">van de Beek D, de Gans J, Tunkel AR, Wijdicks EF (2006) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=16394301 Community-acquired bacterial meningitis in adults.] ''N Engl J Med'' 354 (1):44-53. [http://dx.doi.org/10.1056/NEJMra052116 DOI:10.1056/NEJMra052116] PMID: [http://pubmed.gov/16394301 16394301]</ref>
+* [[Dexamethasone]] should not be administered to patients who have already received animicrobial therapy because it is unlikely to improve clinical outcome.<ref name="pmid15494903">Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15494903 Practice guidelines for the management of bacterial meningitis.] ''Clin Infect Dis'' 39 (9):1267-84. [http://dx.doi.org/10.1086/425368 DOI:10.1086/425368] PMID: [http://pubmed.gov/15494903 15494903]</ref>
+==Antimicrobial Regimen==
+{{ID-Bacterial meningitis}}
+{{ID-Tuberculous meningitis}}
+{{ID-Parasitic meningitis}}
+{{ID-Fungal meningitis}}
+{{ID-Viral meningitis}}
 ==References==
 {{reflist|2}}
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+[[Category:Infectious Disease Project]]
-{{WikiDoc Sources}}
+[[Category:Emergency medicine]]
-[[Category:Disease]]
-[[Category:Infectious disease]]
 [[Category:Neurology]]
-[[Category:Emergency medicine]]

Meningitis medical therapy: Difference between revisions

Latest revision as of 22:42, 29 July 2020

Overview

Principles of Therapy for Bacterial Meningitis

Factors Determining Antimicrobial Activity

Duration of Antimicrobial Therapy

Adjunctive Dexamethasone Therapy

Antimicrobial Regimen

References

References

References

References

References

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