• Am. J. Respir. Crit. Care Med. · Nov 2012

    Comparative Study

    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, and Won-Jung Koh.
    • Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Irwon-ro 81, Gangnam-gu, Seoul, South Korea.
    • Am. J. Respir. Crit. Care Med.. 2012 Nov 1;186(9):917-25.

    RationaleMacrolides, such as clarithromycin (CLR) and azithromycin (AZM), are frequently the only oral antibiotics that are active against Mycobacterium abscessus and M. massiliense infections.ObjectivesTo compare the activity of CLR and AZM in experimental models.MethodsWe compared the treatment efficacies of CLR and AZM and 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 ResultsIn all tested M. abscessus isolates, a high level of inducible CLR 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 CLR MIC on Day 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.ConclusionsCLR 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.

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