Evaluation of rifalazil in long-term treatment regimens for tuberculosis in mice

Previous experiments with rifalazil (RLZ) (also known as KRM-1648) in combi nation with isoniazid (WW) demonstrated its potential for short-course trea tment of Mycobacterium tuberculosis infection. In this study we investigate d the minimum RLZ-INH treatment time required to eradicate M. tuberculosis in a murine model. RLZ-INH treatment for 6 weeks or longer led to a noncult urable state. Groups of mice treated in parallel were killed following an o bservation period to evaluate regrowth. RLZ-INH treatment for a minimum of 10 weeks was necessary. to maintain a nonculturable state through the obser vation period. Pyrazinamide (PZA) was added to this regimen to determine wh ether the treatment duration could be further reduced. In this model, the a ddition of PZA did not shorten the duration of RLZ-INH treatment required t o eradicate M. tuberculosis from mice. The addition of PZA reduced the numb er of mice in which regrowth occurred, although the reduction was not stati stically significant.