title: Macrolide treatment for Mycobacterium abscessus and Mycobacterium massiliense infection and inducible resistance.
abstract: BACKGROUND
  Macrolides, such as clarithromycin (CLR) and azithromycin (AZM), are frequently the only oral antibiotics that are active against Mycobacterium abscessus and M. massiliense infections.
  
  
  OBJECTIVE
  To compare the activity of CLR and AZM in experimental models.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  In 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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Go-Eun
authors.initials: GE
authors.lastname: Choi
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.forename: Choul-Jae
authors.initials: CJ
authors.lastname: Won
authors.forename: Ki-Nam
authors.initials: KN
authors.lastname: Min
authors.forename: Taegwon
authors.initials: T
authors.lastname: Oh
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Hahn
authors.forename: Keehoon
authors.initials: K
authors.lastname: Lee
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Charles L
authors.initials: CL
authors.lastname: Daley
authors.forename: Seonwoo
authors.initials: S
authors.lastname: Kim
authors.forename: Byeong-Ho
authors.initials: BH
authors.lastname: Jeong
authors.forename: Kyeongman
authors.initials: K
authors.lastname: Jeon
authors.forename: Won-Jung
authors.initials: WJ
authors.lastname: Koh
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D017963:Azithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D001854:Bone Marrow Cells; D017291:Clarithromycin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D018942:Macrolides / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009161:Mycobacterium / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D056910:Republic of Korea
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; D017963:Azithromycin; D017291:Clarithromycin