Tuberculous meningitis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The treatment of TB meningitis is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, followed by isoniazid and rifampicin alone for a further ten months. Steroids are always used in the first six weeks of treatment (and sometimes for longer). A few patients may require immunomodulatory agents such as thalidomide. Treatment must be started as soon as there is a reasonable suspicion of the diagnosis. Treatment must not be delayed while waiting for confirmation of the diagnosis.

Antimicrobial Regimen

• Tuberculous meningitis (TB meningitis)

• First-line therapy (dosing information: [2][3][4])

• Isoniazid
• Rifampin
• Rifabutin
• Pyrazinamide
• Ethambutol

• Second-line therapy (dosing information: [5][6][7])

• Cycloserine
• Ethionamide
• Streptomycin
• Amikacin
• Kanamycin
• Capreomycin
• p-Aminosalicylic acid
• Levofloxacin
• Moxifloxacin
• Gatifloxacin

• Tuberculous meningitis caused by susceptible Mycobacterium tuberculosis

• 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.

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

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

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

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

• Isoniazid monoresistance

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

• Rifampin monoresistance

• 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)

• 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)

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