Andreas H Diacon, MD, from Stellenbosch University in Cape Town, South Africa, and colleagues assessed the suitability for future development of new multiple-agent combinations over the first 14 days of treatment in treatment-naive, drug-susceptible patients with uncomplicated pulmonary tuberculosis. Patients were randomly allocated to receive bedaquiline, bedaquiline-pyrazinamide, PA-824-pyrazinamide, bedaquiline-PA-824, PA-824-moxifloxacin-pyrazinamide, or unmasked standard anti-tuberculosis treatment, and the EBA was assessed.
The researchers found that the mean 14-day EBA for PA-824-moxifloxacin-pyrazinamide was comparable to that of standard treatment and was significantly higher than that of bedaquiline, bedaquiline-pyrazinamide, and bedaquiline-PA-824, but not PA-824-pyrazinamide. Treatments appeared safe and were well tolerated. One patient was withdrawn from PA-824-moxifloxacin-pyrazinamide due to excessive corrected QT interval changes.
“A regimen not containing isoniazid and rifampicin would represent a substantial step towards a new regimen with low interaction potential suitable for both fully drug-susceptible and multidrug resistant tuberculosis,” the authors write. “With this study the path to the construction of new regimens becomes clearer.”
One author disclosed being a consultant to Otsuka and Tibotec regarding development of anti-tuberculosis agents.