Comparative in vitro activities of rifamycin analogues against rifampin-sensitive and rifampin-resistant Mycobacterium tuberculosis.
Because of widespread emergence of multidrug resistant Mycobacterium tuberculosis worldwide, there is an urgent need for new bactericidal drugs against this organism. Several new analogues of rifamycin are being developed. Susceptibilities of five of the most potent analogues were determined simultaneously on ten isolates each of rifampin-sensitive and rifampin-resistant M. tuberculosis using the radiometric method (BACTEC) with [C(14)]palmitic acid. Against rifampin-sensitive isolates, all five analogues exhibited inhibitory activity, the most potent being KRM-1648, with MICs varying between 0.003 and 0.02S mug/ml (MICs of rifampin were between 0.05 and 0.4 mug/ml). Similar observations were also obtained for the MBCs of these five analogues-KRM-1648 was most potent, with nine out of ten isolates exhibiting a MBC/MIC ratio of 1.0. Among the rifampin-resistant isolates of M. tuberculosis, the most potent rifampicin analogue was, again, KRM-1648, with seven out of ten isolates exhibiting MBC/MIC ratio of 1.0 and the remaining three exhibiting a ratio of 2.0. These results suggests that KRM-1648 should further be explored in the treatment of tuberculosis patients.
Dhopie
A M
AM
Department of Biological Sciences, Florida Institute of Technology, Melbourne, FL 32 901-6975, USA. adhopie@fit.edu
Dhople
A A
AA
Ibanez
M A
MA