Macrolide treatment for mycobacterium abscessus and mycobacterium massiliense infection and inducible resistance

Go Eun Choi, Sung Jae Shin, Choul Jae Won, Ki Nam Min, Taegwon Oh, Mi Young Hahn, Keehoon Lee, Soo Hyun Lee, Charles L. Daley, Seonwoo Kim, Byeong Ho Jeong, Kyeongman Jeon, Won Jung Koh

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Abstract

Rationale: Macrolides, such as clarithromycin (CLR) and azithromycin (AZM), are frequently the only oral antibiotics that are active against Mycobacterium abscessus and M. massiliense infections. Objectives: To compare the activity of CLR and AZM in experimental models. Methods:We compared the treatment efficacies of CLR andAZMand determined the correlation between efficacy and induced erythromycin ribosome methyltransferase gene (erm)(41) expression in experimental models of M. abscessus and M. massiliense infections. Measurements and Main Results: In all tested M. abscessus isolates, a highlevel of inducibleCLR resistance developed(minimal inhibitory concentration [MIC] on Day 3 versus Day 14; P,0.001).Whereas the AZM MIC increased on Day 14 (P , 0.01 versus Day 3), the level was significantly lower than the CLRMIC onDay 14 (P,0.001). However, the MICs of CLR and AZM for the M. massiliense isolates did not change. Compared with CLR, AZM presented greater antibiotic activity against M. abscessus in vitro, ex vivo, and in vivo (P , 0.05), whereas both macrolides were comparably effective against M. massiliense. In M. abscessus infection, the level of erm(41) expression was higher after exposure to CLR than after exposure to AZM (P , 0.001). Experiments using an erm(41)-knockout M. abscessus mutant and an M. massiliense transformant expressing M. abscessus erm(41) confirmed that erm(41) was responsible for inducible CLR resistance. Conclusions: CLR induces greater erm(41) expression and thus higher macrolide resistance than AZM in M. abscessus infection. AZM may be more effective against M. abscessus, whereas both macrolides appear to be equally effective against M. massiliense.

Original languageEnglish
Pages (from-to)917-925
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume186
Issue number9
DOIs
Publication statusPublished - 2012 Nov 1

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All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Choi, G. E., Shin, S. J., Won, C. J., Min, K. N., Oh, T., Hahn, M. Y., Lee, K., Lee, S. H., Daley, C. L., Kim, S., Jeong, B. H., Jeon, K., & Koh, W. J. (2012). Macrolide treatment for mycobacterium abscessus and mycobacterium massiliense infection and inducible resistance. American Journal of Respiratory and Critical Care Medicine, 186(9), 917-925. https://doi.org/10.1164/rccm.201111-2005OC