Activities of eighteen antimicrobial regimens against Mycobacterium avium infection in beige mice

Abstract

The therapeutic effect of 18 anti-Mycobacterium avium regimens was examined in beige mice after 91 days of infection. Treatments included monotherapy with clarithromycin (CLA), ethambutol (EMB), amikacin (AMI), rifabutin (RFB), ciprofloxacin (CIP), clofazimine (CLO), and combinations of CLA, CLA-EMB, or CLA-AMI with one of the other drugs. After monotherapy, only AMI and CLA displayed bacteriostatic and/or moderate bactericidal effects in spleens and lungs, while CIP and RFB were totally inactive and CLO and EMB showed intermediate effects against the isolate tested. Resistant mutants were isolated in spleens of mice treated with EMB, CIP, RFB, and CLO-Among two-drug combinations, CLA-RFB, CLA-CIP, and CLA-CLO were significantly more active than RFB, CIP, CLO, respectively, but not more active than CLA alone, in both organs; CLA-AMI and CLA-EMB were bactericidal in spleens and lungs, respectively. Although activity of CLA-EMB was significantly potentiated by RFB and CLO in spleens and lungs, that of CLA-AMI was significantly increased by RFB and CLO only in lungs. The most active regimen in spleens and lungs on day 91 was the combination of all three, namely CLA-AMI-EMB, which reduced the CFU numbers of 2.7 and 7.5 log10, in comparison with day 1 and day 91 counts in untreated control mice, respectively.