Activities of eighteen antimicrobial regimens against Mycobacterium avium infection in beige mice
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Published on: October 25, 2024
L Fattorini1, Y Xiao, M Mattei
1Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Rome, Italy.
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.
Insights
This study evaluated 18 anti-Mycobacterium avium treatment regimens in mice. The combination of clarithromycin, amikacin, and ethambutol (CLA-AMI-EMB) was the most effective, significantly reducing bacterial load in spleen and lungs.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Mycobacterium avium complex (MAC) infections pose a significant therapeutic challenge.
- Developing effective treatment regimens for MAC is crucial, especially for disseminated infections.
Purpose of the Study:
- To evaluate the in vivo efficacy of various anti-Mycobacterium avium treatment regimens.
- To identify optimal drug combinations for treating M. avium infection in a murine model.
Main Methods:
- Beige mice were infected with M. avium for 91 days.
- Therapeutic efficacy was assessed for 18 regimens, including monotherapies and drug combinations.
- Bacterial burden was quantified in spleen and lungs via colony-forming units (CFU).
Main Results:
- Monotherapy with amikacin (AMI) and clarithromycin (CLA) showed moderate bactericidal effects.
- Combinations like clarithromycin-amikacin (CLA-AMI) and clarithromycin-ethambutol (CLA-EMB) demonstrated bactericidal activity.
- The triple combination of clarithromycin-amikacin-ethambutol (CLA-AMI-EMB) was the most potent, significantly reducing CFU counts in both spleen and lungs.
Conclusions:
- Combined therapies, particularly triple combinations, are superior to monotherapies for M. avium infection.
- The CLA-AMI-EMB regimen shows significant promise as a highly effective treatment strategy.
- Further research into optimizing combination therapies for MAC infections is warranted.
