Time-kill kinetics of slowly growing mycobacteria common in pulmonary disease.

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.

• 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)
• 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

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