Tuberculosis is currently treated with a 6-month course regimen. During this time many patients might fail to adhere to treatment and default, increasing the risk of recurrent disease which might be multidrug resistant. A shorter duration of treatment is expected to provide improved patient compliance and at least equal or better clinical outcome. The aim of the trial is to evaluate the efficacy and safety of a gatifloxacin-containing regimen of four months duration for the treatment of pulmonary tuberculosis.

Standard multiple ascending dose Phase I study evaluating PK and safety. 14 day dose-escalation complete; 28 day study in healthy volunteers also completed May 2010. PNU-100480 is being developed for the treatment of both drug resistant and sensitive tuberculosis. This is an efficacy and safety study to characterize the effect of PNU-100480 when given for 14 days to treatment-naive patients with drug-sensitive pulmonary tuberculosis.

Over 7000 actinomycetes were fermented in 3 different media and extracted with 3 solvents. All were screened against M. tuberculosis for growth inhibition. Actives were profiled for potency and selectivity and 20 were scaled up for primary fractionation. Based on activity on primary fractions, 2 were scaled up for isolation of active principles. Ecumicin has demonstrated an excellent in vitro profile, activity vs. M. tb in mice at 20-32 mg/kg ip and subsequently shown to have some degree of oral bioavailability.

This project aims to develop compounds that kill M.tb by inhibiting DNA gyrase. DNA gyrase, an important enzyme found in all bacteria, is a proven target for antibacterial chemotherapy. Fluoroquinolones, a class of synthetic antimicrobial agents that have demonstrated activity in TB treatment, kill bacteria by inhibiting bacterial DNA gyrase and topoisomerase IV in most bacterial species.