Key considerations in the pharmacotherapy of tuberculous meningitis

Figures & data

Figure 1. Potential therapeutic strategies for improving outcomes in TBM.

Table 1. Summary of completed trials of higher dose rifampicin in TBM^a.

Reference number	Study design	Rifampicin experimental dose	Population	Key findings
[6]	RCT: open label, factorial	13 mg/kg (600 mg) IV (with or without additional moxifloxacin 400 mg or 800 mg)^b	Adults Indonesia n = 60 HIV 12%	Higher dose rifampicin associated with reduced mortality (65%) compared to standard dose (35%); p = 0.03 Not powered for clinical endpoint
[5]	RCT: open label	17 mg/kg (750 mg) PO 20 mg/kg (900 mg) PO 13 mg/kg (600 mg) IV	Adults Indonesia n = 30 HIV 20%	Similar PK exposures between intravenous (IV) and both oral (PO) doses Clinical efficacy endpoints not assessed
[7]	RCT: double blind, placebo-controlled	15 mg/kg PO (with added levofloxacin)^b for 2 months	Adults Vietnam n = 817 HIV 43%	No difference in primary mortality endpoint at 9 months
[4]	RCT: double-blind, placebo-controlled	20 mg/kg (900 mg) PO 30 mg/kg (1350 mg) PO^b	Adults Indonesia n = 60 HIV 10%	Trend towards lower mortality with rifampicin 30 mg/kg (15%) vs. standard dose (35%) at 6 months; not significant. Not powered for clinical endpoint

RCT, randomized controlled trial; IV, intravenous; PO, oral.

^aAll participants received standard antitubercular therapy plus corticosteroids.

^bCompared to standard dose rifampicin (10 mg/kg).

Table 2. Summary of completed trials of adjunctive aspirin in TBM.

Reference number	Study design	Intervention	Population	Key findings
[19]	RCT: double-blind, placebo-controlled	Aspirin 81 mg vs. 1000 mg vs. placebo for 60 days^a	Adults HIV-uninfected Vietnam n = 120	No difference in primary efficacy endpoint (new brain infarction or death at 60 days) Reduced infarcts and death with aspirin 81 mg (15%) and 1000 mg (11%) compared to placebo (34%) in subgroup with confirmed TBM; p = 0.06
[20]	RCT: open label, placebo- controlled	Aspirin 150 mg vs. placebo for 3 months^b	Adults HIV-uninfected India n = 118	No difference in primary outcome of stroke (MRI or clinical) at 3 months Significant reduction in mortality with aspirin (22%) compared to placebo (43%); p = 0.02
[21]	RCT: double-blind, placebo-controlled	Aspirin 75 mg vs. aspirin 100 mg/kg vs. placebo for 1 month^a	Children HIV-infected (n = 5) and uninfected South Africa n = 146	Aspirin not associated with improved neurological or cognitive outcomes, or survival at 6 months Study not powered for clinical endpoint

RCT, randomized controlled trial.

^aAll participants received standard antitubercular therapy plus corticosteroids.

^bCorticosteroids administered only to participants with severe disease.

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