Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: a phase 2b, open-label, partly randomised trial in patients with drug-susceptible or drug-resistant pulmonary tuberculosis

Rifamycin action on RNA polymerase in antibiotic-tolerant Mycobacterium tuberculosis results in differentially detectable populations

“…4A). PA-824 (pretomanid), a drug showing promise in clinical trials (26,27), minimally impacted 2 wk-starved Mtb at doses at or below 5.5 μM and did not create DD Mtb under those conditions (Fig. 4B).…”

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…Pretomanid is in phase 3 testing, and its characteristics are shown in table 7. On the basis of early bactericidal activity studies 355 and the superior bactericidal activity of pretomanid, moxifloxacin, and pyrazinamide versus rifampicin, isoniazid, pyrazinamide, and ethambutol for drug-sensitive tuberculosis at 8 weeks, 379 the phase 3 STAND study was launched (table 6; NCT02342886), but this study was placed on partial clinical hold because of hepatotoxicity and further enrolment was stopped, but follow up will continue as per protocol. Pretomanid is also being studied as part of combination therapy for XDR tuberculosis (NiX Trial, NCT02333799; table 6).…”

“…The combination of pretomanid with moxifloxacin and pyrazinamide was first shown to be superior to the first-line regimen for drugsusceptible tuberculosis in a murine model 388 and has subsequently shown activity that is superior to the standard of care over the first 2 months of treatment in patients with drug-susceptible tuberculosis. 379 Pyrazinamide also appeared to be effective in patients with pyrazinamide-susceptible and fluoroquinolonesusceptible MDR tuberculosis. 379 A confirmatory phase 3 study of pyrazinamide in patients with MDR tuberculosis is underway (China PZA trial; table 6).…”

“…379 Pyrazinamide also appeared to be effective in patients with pyrazinamide-susceptible and fluoroquinolonesusceptible MDR tuberculosis. 379 A confirmatory phase 3 study of pyrazinamide in patients with MDR tuberculosis is underway (China PZA trial; table 6). Similarly, follow ing the promising effects in mice, the three-drug combin ation of bedaquiline, pretomanid, and pyrazinamide is under investigation in patients with drug-sensitive tuberculosis, with the addition of moxifloxacin in patients with MDR tuberculosis (STAND; table 6).…”

Novel Treatments for Drug-Resistant Tuberculosis

“…To date, pretomanid remains a promising new agent with the potential to change the approach to drug-resistant TB, particularly when used as a component of novel treatment regimens. 35,37 sutezolid Sutezolid is a novel oxazolidinone undergoing premarketing evaluation, which -similar to linezolid, itself a first-generation oxazolidinone -exerts bactericidal activity by inhibiting bacterial protein synthesis. 38 Sutezolid has antimycobacterial activity, and in a murine model, it was found to be more potent than linezolid against M. tuberculosis.…”