한빛사 논문
Go-Eun Choi1, Sung Jae Shin2,*, Choul-Jae Won2, Ki-Nam Min1, Taegwon Oh2,4 , Mi-Young Hahn3, Keehoon Lee2, Soo Hyun Lee4, Charles L. Daley5, Seonwoo Kim6,5 ,Byeong-Ho Jeong7, Kyeongman Jeon7, Won-Jung Koh7,*
1 Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Korea;
2 Department of Microbiology and Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea;
3 Department of Systems Biology and Institute of Life Science and Biotechnology, Yonsei University, Seoul, Korea;
4 Biomolecules Function Research Center, Korea Institute of Science and Technology, Seoul, Korea;
5 Division of Mycobacterial and Respiratory Infections, Department of Medicine, National Jewish Health, Denver, Colorado, United States;
6 Biostatistics team, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea;
7 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
* Correspondence and requests for reprints should be addressed to Sung Jae Shin and Won-Jung Koh
Abstract
Rationale: Macrolides, such as clarithromycin (CLR) and azithromycin (AZM), are frequently the only oral antibiotics that are active against Mycobacterium abscessus and Mycobacterium massiliense infections. Neither CLR nor AZM have previously been demonstrated to provide superior treatment efficacy for these infections.
Objectives: We compared the treatment efficacies of CLR and AZM and determined the correlation between efficacy and induced erm(41) expression in experimental models of M. abscessus and M. massiliense infections.
Measurements and Main Results: In all tested M. abscessus isolates, a high level of inducible CLR resistance developed (minimal inhibitory concentration [MIC] on day 3 vs. day 14; P<0.001). Whereas the AZM MIC increased on day 14 (P<0.01 vs. 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 to 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 following exposure to CLR than following 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.
Key words: Mycobacterium abscessus, Mycobacterium massiliense, clarithromycin, azithromycin, treatment efficacy, inducible resistance, erm(41)
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
관련분야 논문보기
해당논문 저자보기