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

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 C LA 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 iso lated in spleens of mice treated with EMB, CIP, RFB, and CLO. Among two-dru g combinations, CLA-RFB, CLA-CIP, and CLA-CLO were significantly more activ e 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, re spectively. Although activity of CLA-EMB was significantly potentiated by R FB and CLO in spleens and lungs, that of CLA-AMI was significantly increase d by RFB and CLO only in lungs. The most active regimen in spleens and lung s on day 91 was the combination of all three, namely CLA-AMI-EMB, which red uced the CFU numbers of 2.7 and 7.5 log(10) in comparison with day 1 and da y 91 counts in untreated control mice, respectively.