Activity of rifapentine and its metabolite 25-O-desacetylrifapentine compared with rifampicin and rifabutin against Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis and M-bovis BCG

The in vitro activity of rifapentine and its metabolite, 25-O-desacetylrifa pentine, as compared with that of rifampicin and rifabutin, was determined against Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis and M. bovis BCG. MICs were determined radiometrically and by the 1% proportional method using Middlebrook 7H11 agar. The bactericidal effect of the drugs was determined in parallel at selected concentrations. For drug- susceptible isolates of M. tuberculosis, the Bactec MICs of rifapentine and 25-O-desacetylrifapentine were 0.03-0.06 mg/L and 0.125-0.25 mg/L, respect ively. Similar MICs were obtained for M. africanum (0.03-0.125 and 0.125-0. 50 mg/L, respectively), and M. bovis (0.063-0.25 and 0.125-1.0 mg/L, respec tively), but MICs were considerably lower for M. bovis BCG (0.008-0.063 mg/ L for rifapentine and 0.016-0.125 mg/L for its metabolite). In general, MIC s determined using 7H11 agar medium were usually one or two dilutions highe r than those obtained using Bactec broth. When compared with rifampicin and rifabutin, the inhibitory activity of rifapentine for drug-susceptible iso lates was roughly equal to that of rifabutin, and the inhibitory activity o f 25-O-desacetylrifapentine was comparable to that of rifampicin; however, rifapentine was somewhat more bactericidal than rifabutin at equal concentr ations. Clinical isolates of M tuberculosis with a high degree of resistanc e to rifampicin (MIC, 32 mg/L) were also highly resistant to rifabutin, rif apentine and 25-O-desacetylrifapentine, although the MICs of rifabutin in t his case were somewhat lower than the MICs of rifapentine.