New drugs for TB.
In this prospective, randomised, early bactericidal activity (EBA) study, treatmentnaive, drug-susceptible patients with uncomplicated pulmonary tuberculosis were admitted to hospitals in Cape Town, South Africa, between 7 October 2010 and 19 August 2011. Patients were randomised centrally by computer-generated randomisation sequence to receive bedaquiline, bedaquiline-pyrazinamide, PA-824-pyrazinamide, bedaquiline-PA-824, PA-824-moxifloxacinpyrazinamide, or unmasked standard antituberculosis treatment as positive control. The primary outcome was the 14-day EBA assessed in a central laboratory from the daily fall in colony-forming units (CFU) of M. tuberculosis per milliliter of sputum in daily overnight sputum collections. Clinical staff were partially masked but laboratory personnel were fully masked.
The mean 14-day EBA of PA-824-moxifloxacin-pyrazinamide (n=13; 0.233 [SD 0.128]) was significantly higher than that of bedaquiline (14; 0.061 [0.068]), bedaquiline-pyrazinamide (15; 0.131 [0.102]), bedaquiline-PA-824 (14; 0.114 [0.050]), but not PA-824-pyrazinamide (14; 0.154 [0.040]), and comparable with that of standard treatment (10; 0.140 [0.094]). Treatments were well tolerated and appeared safe. One patient on PA-824-moxifloxacin-pyrazinamide was withdrawn because of corrected QT interval changes exceeding criteria pre-specified in the protocol.
PA-824-moxifloxacin-pyrazinamide is potentially suitable for treating drug-sensitive and multidrug-resistant tuberculosis. Multiagent EBA studies can contribute to reducing the time needed to develop new antituberculosis regimens.
Diacon AH, et al. The Lancet, Early Online Publication,
23 July 2012. [http://dx.doi.org/10.1016/S0140-6736(12)61080-0]
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|Publication:||CME: Your SA Journal of CPD|
|Date:||Aug 1, 2012|
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