Safety, Efficacy, and Pharmacokinetics of Daily Optimized Doses of Rifampicin for the Treatment of Tuberculosis: A Systematic Review and Bayesian Network Meta-Analysis
Abstract
BACKGROUND: Higher than standard doses of rifampicin could improve the treatment outcome of drug-susceptible tuberculosis (TB) without compromising the safety of patients. METHODS: We performed a systematic review of prospective clinical studies including adults with pulmonary and extrapulmonary TB receiving rifampicin doses above 10 mg/kg/day. We extracted the data on overall adverse events (AE), hepatic AE, sputum culture conversion (SCC) at week 8, recurrence, mortality, and pharmacokinetics. We performed a Bayesian network meta-analysis (NMA) using a random-effects model. RESULTS: In 19 studies, 2033 out of 3654 participants received rifampicin doses higher than 10 mg/kg/day. The NMA showed an increased risk of overall and hepatic AE for the 40 mg/kg/day dose (risk ratio [RR] 4.8, 95% credibility interval [CrI]: 1.1, 25, and 15.00; 95% CrI: 1.1, 58.0, respectively), but no other doses, including 50 mg/kg/day showed such an increase. Increasing doses improved sputum culture conversion at week 8 (RR 1.3, 95% CrI: 1.1, 1.7 for SCC with 35 mg/kg/day). CONCLUSIONS: Optimal doses of rifampicin may be between 25 and 35 mg/kg/day, but should be tailored at the individual or, at least, at the population level.
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 3,654 participants or records.
Read the paper
Related studies
- Synthesis, In Vitro and In Silico Molecular Docking Studies of Novel Phthalimide–Pyrimidine Hybrid Analogues to Thalidomide as Potent Antitubercular Agents
- Exploring the inhibitory performance of expired moxifloxacin and norfloxacin on copper corrosion in saline environment
- Molecular investigation of antimicrobial peptides against Helicobacter pylori proteins using a peptide-protein docking approach
- Screening of novel narrow-spectrum benzofuroxan derivatives for the treatment of multidrug-resistant tuberculosis through in silico, in vitro, and in vivo approaches
- Synthesis, Characterization, Anticancer, Antioxidant, and In Silico Evaluation of Semicarbazides and Thiosemicarbazides
- Fast and accurate prediction of drug induced proarrhythmic risk with sex specific cardiac emulators
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.