High-Dose Rifampin Not Beneficial for Tuberculosis Meningitis

FRIDAY, Dec. 19, 2025 (HealthDay News) — No benefit of high-dose versus standard-dose rifampin is seen among adults with tuberculosis meningitis, according to a study published online Dec. 17 in the New England Journal of Medicine.

David B. Meya, M.B., Ch.B., Ph.D., from Makerere University in Uganda, and colleagues conducted a randomized, placebo-controlled clinical trial involving adults with tuberculosis meningitis in Indonesia, South Africa, and Uganda to examine whether high-dose rifampin could improve survival outcomes. Participants with and without HIV coinfection were randomly assigned to receive eight weeks of standard daily isoniazid, rifampin (10 mg/kg body weight), ethambutol, and pyrazinamide plus either additional rifampin (for a cumulative dose of 35 mg/kg; high-dose group) or matched placebo (standard-dose group; 249 and 250 participants, respectively).

The researchers found that 109 (44.6 percent) and 100 participants (40.7 percent) in the high-dose and standard-dose groups, respectively, died during six months of follow-up (hazard ratio, 1.17; 95 percent confidence interval, 0.89 to 1.54). The median time to death was 13 and 24 days in the high-dose and standard-dose groups, respectively, among those who died within six months. Drug-induced liver injury occurred in 8.0 and 4.4 percent of participants in the high-dose and standard-dose groups, with no deaths from drug-induced liver injury.

“It was, of course, disappointing that this is not the solution. But these are important results — we now know we need to take a different path. That’s how science works,” coauthor Reinout van Crevel, M.D., Ph.D., from the University of Oxford in the United Kingdom, said in a statement.

One coauthor disclosed financial ties to the biopharmaceutical industry.

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