prothionamide and bedaquiline

Short-course regimens for multidrug-resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug bedaquiline (BDQ) may have the potential to shorten MDR-TB treatment to less than 6 months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modeling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modeling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (4 months) while still maintaining a very high treatment success rate (100% for daily BDQ for 2 weeks, or 95% for daily BDQ for 1 week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes, then we anticipate clear cost savings and a subsequent improvement in the efficiency of national TB programs.

Topics: Antitubercular Agents; Clofazimine; Colony Count, Microbial; Computer Simulation; Diarylquinolines; Dose-Response Relationship, Drug; Drug Dosage Calculations; Drug Resistance, Bacterial; Drug Therapy, Combination; Ethambutol; Host-Pathogen Interactions; Humans; Immunity, Innate; Isoniazid; Kanamycin; Macrophages; Microbial Sensitivity Tests; Models, Statistical; Moxifloxacin; Mycobacterium tuberculosis; Ofloxacin; Prothionamide; Pyrazinamide; Time Factors; Tuberculosis, Multidrug-Resistant