Abstract | OBJECTIVES: This study aimed to provide basic pharmacodynamic information for key antibiotics used to treat Mycobacterium avium and Mycobacterium xenopi pulmonary disease. METHODS: M. avium subspecies hominissuis IWGMT49 and M. xenopi ATCC 19250 type strains were used; the MICs of clarithromycin, amikacin and moxifloxacin were determined by broth microdilution. Time-kill assays were performed, exposing bacteria to 2-fold concentrations from 0.062× to 32× the MIC at 37°C for 240 h for M. avium or 42 days for M. xenopi. The sigmoid maximum effect (Emax) model was fitted to the time-kill curve data. RESULTS: Maximum killing of M. avium by amikacin was obtained between 24 and 120 h (0.0180 h(-1)) and was faster and higher than with clarithromycin (0.0109 h(-1)); however, regrowth and amikacin-resistant mutants were observed. Killing rates for M. xenopi were higher, 0.1533 h(-1) for clarithromycin and 0.1385 h(-1) for moxifloxacin, yet required 42 days. There were no significant differences between the Hill's slopes determined for all of the antibiotics tested against M. avium or M. xenopi (P = 0.9663 and P = 0.0844, respectively). CONCLUSIONS: The killing effect of amikacin and clarithromycin on M. avium subspecies hominissuis was low, although amikacin activity was higher than that of clarithromycin, supporting its role in a combined therapy. Clarithromycin and moxifloxacin may have similar activity within treatment regimens for M. xenopi disease. Future studies of in vitro and in vivo pharmacokinetic/pharmacodynamic interactions are needed to improve the current regimens to treat these two important slowly growing mycobacteria in pulmonary disease.
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Authors | Beatriz E Ferro, Jakko van Ingen, Melanie Wattenberg, Dick van Soolingen, Johan W Mouton |
Journal | The Journal of antimicrobial chemotherapy
(J Antimicrob Chemother)
Vol. 70
Issue 10
Pg. 2838-43
(Oct 2015)
ISSN: 1460-2091 [Electronic] England |
PMID | 26142475
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected]. |
Chemical References |
- Anti-Bacterial Agents
- Amikacin
- Clarithromycin
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Topics |
- Amikacin
(pharmacology)
- Anti-Bacterial Agents
(pharmacology)
- Clarithromycin
(pharmacology)
- Dose-Response Relationship, Drug
- Drug Resistance, Bacterial
- Microbial Sensitivity Tests
- Mutation
- Mutation Rate
- Mycobacterium avium
(drug effects, genetics)
- Mycobacterium xenopi
(drug effects)
- Time Factors
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