An In Vitro Perspective on What Individual Antimicrobials Add to Mycobacterium avium Complex Therapies

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Publication year
2021Source
Antimicrobial Agents and Chemotherapy, 65, 8, (2021), article e0273020ISSN
Publication type
Article / Letter to editor

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Organization
Medical Microbiology
Clinical Pharmacy
Pulmonary Diseases
Journal title
Antimicrobial Agents and Chemotherapy
Volume
vol. 65
Issue
iss. 8
Subject
Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health SciencesAbstract
For Mycobacterium avium complex pulmonary disease (MAC-PD), current treatment regimens yield low cure rates. To obtain an evidence-based combination therapy, we assessed the in vitro activity of six drugs, namely, clarithromycin (CLR), rifampin (RIF), ethambutol (EMB), amikacin (AMK), clofazimine (CLO), and minocycline (MIN), alone and in combination, against Mycobacterium avium and studied the contributions of individual antibiotics to efficacy. The MICs of all antibiotics against M. avium ATCC 700898 were determined by broth microdilution. We performed kinetic time-kill assays of all single drugs and clinically relevant two-, three-, four-, and five-drug combinations against M. avium. Pharmacodynamic interactions of these combinations were assessed using area under the time-kill curve-derived effect size and Bliss independence. Adding a second drug yielded an average increase of the effect size (E) of 18.7% ± 32.9%, although antagonism was seen in some combinations. Adding a third drug showed a smaller increase in effect size (+12.2% ± 11.5%). The RIF-CLO-CLR (E of 102 log(10) CFU/ml · day), RIF-AMK-CLR (E of 101 log(10) CFU/ml · day), and AMK-MIN-EMB (E of 97.8 log(10) CFU/ml · day) regimens proved more active than the recommended RIF-EMB-CLR regimen (E of 89.1 log(10) CFU/ml · day). The addition of a fourth drug had little impact on effect size (+4.54% ± 3.08%). In vitro, several two- and three-drug regimens are as effective as the currently recommended regimen for MAC-PD. Adding a fourth drug to any regimen had little additional effect. In vitro, the most promising regimen would be RIF-AMK-macrolide or RIF-CLO-macrolide.
This item appears in the following Collection(s)
- Academic publications [227864]
- Electronic publications [107344]
- Faculty of Medical Sciences [86218]
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