Higher Rifampin Dose Effective and Safe in Tuberculosis

Both 15 mg and 20 mg rifampin doses showed a rapid decline in bacteria in patients with tuberculosis.

Higher daily dosages of rifampin are as effective as the standard of care for tuberculosis without increasing adverse effects, according to a recent study published in the American Journal of Respiratory Critical Care Medicine.

Researchers of this phase 2 study examined the efficacy and safety of rifampin when used at dosages of 10, 15, or 20 mg/kg/d. Patients who tested positive for tuberculosis (N=180) were randomly assigned to 1 of 3 treatment groups and then monitored for reductions in Mycobacterium tuberculosis and toxicities.

Both 15 mg and 20 mg doses showed a rapid decline in bacteria. For each 5 mg/kg increase in rifampin dose in the modified intention-to-treat population, the researchers estimated a difference of –0.011 log10 colony forming units/mL/d (95% CI, –0.025 to –0.002 log10 colony forming units/mL/d) in elimination rate between treatment groups (P =.230). Meanwhile, in the per-protocol population, the difference was even higher at –0.022 log10 colony forming units/mL/d (95% CI, –0.046 to –0.002 log10 colony forming units/mL/d; P =.022).

Similar grade 2 adverse event frequencies were also seen across the treatment groups (43.3%, 51.7%, and 38.3% of participants in the 10, 15, and 20 mg/kg/d groups, respectively). The rate of bacterial sterilization was proportionally related to the increase in doses of rifampin. The most common adverse events were hepatic, gastrointestinal, musculoskeletal, and respiratory related. 

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The effects of higher doses of rifampin need to be further evaluated. In this study, the 20 mg/kg/d resulted in only a slightly higher total dose than the 15 mg/kg/d. This was due to the average weight of patients in the 20 mg group being lower than those in the15 mg group. The researchers also did not find a significant difference in the efficacy of the two higher doses, and it was hypothesized that there would be a greater effect if the dosage was increased.


Veláquez GE, Brooks MB, Coit JM, et al. Efficacy and safety of high-dose rifampin in pulmonary tuberculosis: a randomized controlled trial [published online June 29, 2018]. Am J Respir Crit Care Med. doi: 10.1164/rccm.201712-2524OC