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 378C 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.

doi.org/10.1093/jac/dkv180, hdl.handle.net/1765/90537
Journal of Antimicrobial Chemotherapy
Department of Medical Microbiology and Infectious Diseases

Ferro, B.E, van Ingen, J, Wattenberg, M, van Soolingen, D, & Mouton, J.W. (2015). Time-kill kinetics of slowly growing mycobacteria common in pulmonary disease. Journal of Antimicrobial Chemotherapy, 70(10), 2838–2843. doi:10.1093/jac/dkv180