ACTIVITIES OF ROXITHROMYCIN USED ALONE AND IN COMBINATION WITH ETHAMBUTOL, RIFAMPIN, AMIKACIN, OFLOXACIN, AND CLOFAZIMINE AGAINST MYCOBACTERIUM-AVIUM COMPLEX

Preliminary studies showed that roxithromycin possessed significant in vitro activity against a variety of atypical mycobacteria such as the Mycobacterium avium complex, M. scrofulaceum, M. szulgai, M. malmoens e, M. xenopi, M. marinum, and nrl. kansasii and rare pathogens such as M, chelonae and M. fortuitum. In this investigation, radiometric MICs of roxithromycin, ethambutol, rifampin, amikacin, ofloxacin, and clof azimine for 10 clinical isolates of the M. avium complex (5 each from human immunodeficiency virus [HIV]-positive and HIV-negative patients) were determined. Roxithromycin MICs against all the isolates were bel ow the reported maximum concentration of drug in serum at the routine pH of 6.8, and the MICs were further lowered by 1 to 2 dilutions at a pH of 7.4. In vitro enhancement of roxithromycin activity against all strains was further investigated by the previously established Bactec 460-TB method by combining the drugs at sub-MIC levels. Antibacterial activity of roxithromycin was enhanced in all 10 strains by ethambutol , in 3 strains each by rifampin and clofazimine, in 2 strains by amika cin, and in 1 strain bg ofloxacin. In vitro screening of three-drug co mbinations showed that combinations of roxithromycin, ethambutol, and a third potential anti-M. avium drug (rifampin, amikacin, ofloxacin, o r clofazimine) resulted in further enhancement of activity in 13 out o f 20 drug combinations screened.