Postantibiotic effects of rifampin, amikacin, clarithromycin and ethambutol used alone or in various two-, three- and four-drug combinations against Mycobacterium avium

Abstract

The postantibiotic effects (PAEs) of rifampin, amikacin, clarithromycin, and ethambutol were determined radiometrically against five AIDS-associated isolates of Mycobacterium avium, and were found to be 20.8 ± 3.4, 18.4 ± 2.5, 11.8 ± 1.7, and 2.4 ± 0.9 h, respectively. Various two-, three- or four-drug combinations were also screened; the PAEs for a two-drug combination were generally longer than individual drugs (mean PAE of 13.8 ± 1.5 to 29.2 ± 7.4 h instead of 2.4 ± 0.9 to 18.4 ± 2.5 h for single drugs). The addition of a third drug further increased the mean PAE to a range of 21.0 ± 2.6 to 32.4 ± 6.1 h. Both rifampin+clarithromycin and rifampin+amikacin were the most potent two-drug combinations resulting in longer PAEs than individual drugs, whereas rifampin+amikacin+clarithromycin was the most potent three-drug combination. Parallel viable count determinations showed a good correlation between the PAE results obtained by the radiometric method or by bacterial viability assessment. These results are useful in planning future clinical investigations to clarify the possible implication of PAE in drug schedule and dosage, a line of information that is urgently needed to guide the drug administration in M. avium-infected AIDS patients, who are presently over-burdened with the administration of too many drugs for HIV-treatment and opportunistic infections.