A very important aspect of this studyis the increased activity of two-drug combinations containingpyrazinamide. In two previous EBA studies thisdrug had negligible, if any, bactericidal activity in the fi rstdays of treatment.29,31 Similarly, bedaquiline had littlediscernible early activity in this and other studies3 but,with the addition of pyrazinamide, activity occurs muchearlier and at much increased magnitude. Pyrazinamidealso seemed to augment PA-824 activity, which was notmeasured in this study but was quantifi ed recently at thesame centres.4,5 With the addition of pyrazinamide the14-day EBACFU of PA-824 increased from 0·098 to0·154 and the EBATTP increased from 4·494 to 8·805. Insmaller numbers of patients, Jindani and colleagues29showed that the EBACFU of pyrazinamide alone duringdays 0 to 2 was 0·044, but increased to 0·113 from days 2to 14. Similar to this study, the addition of pyrazina mideto isoniazid-streptomycin and isoniazid-rifampicinpyrazinamideregimens led to a signifi cant improvementin early activity (p<0·05 for the period 0–2 days). Whilethe underlying mechanisms need clarifi cation, theseobser vations on the important role played by pyrazinamideraise concerns about currently reported highrates of pyrazinamide resistance in patients withMDR tuberculosis.9
การแปล กรุณารอสักครู่..
