In VitroActivity of Clarithromycin Alone or in Combination with Other Antimicrobial Agents againstMycobacterium avium-intracellulare.Complex Strains Isolated from AIDS Patients

Abstract

The activity of clarithromycin and five other antimicrobial agents, namely amikacin, rifampicin, rifabutin, clofazimine and ciprofloxacin, was assessed both by an agar dilution and a radiometric method in broth on 11 Mycobacterium avium-intracellulare complex (MAC) strains, recently isolated from AIDS patients. Minimum inhibitory concentrations (MICs) radiometrically determined were, in general, several times lower than MICs assessed in agar, probably because of a partial degradation of antimicrobials during the long incubation period needed for tests in solid medium. When tested in broth, rifabutin and clofazimine showed very low MICs 90 (0.24 and 0.78 microgram/ml, respectively). Ciprofloxacin and clarithromycin also had MICs90 in the range of peak serum levels (1.93 and 3.76 micrograms/ml, respectively). Moreover, all these antimicrobials are known to concentrate several times in macrophages. MICs90 were higher for amikacin (11 micrograms/ml) and for rifampicin (8 micrograms/ml). When clarithromycin was tested against three MAC strains in combination with another drug, it showed a synergistic effect only when combined with rifampicin. Some synergistic effect was observed also when combining clarithromycin with rifampicin and amikacin, whereas in combination with rifabutin and clofazimine there was only an additive effect.

Tolerance and Pharmacokinetic Interactions of Rifabutin and Clarithromycin in Human Immunodeficiency Virus-Infected Volunteers

“…Rifabutin was effective for MAC prophylaxis in a placebo-controlled, double-blind trial (31). The combination of rifabutin and clarithromycin was found to have additive activity in vitro (23,26) in macrophages (27) and the beige mouse model (24).…”