title: Successful antibiotic treatment of pulmonary disease caused by Mycobacterium abscessus subsp. abscessus with C-to-T mutation at position 19 in erm(41) gene: case report.
abstract: Mycobacterium abscessus complex (MABC) is the most drug resistant of the mycobacterial pathogens. M. abscessus subsp. abscessus encodes a functional erythromycin ribosomal methylase gene, erm(41), causing inducible macrolide resistance. However, some clinical isolates of M. abscessus subsp. abscessus harboring nonfunctional erm(41) were susceptible to macrolide, even after extended incubation of 14 days. Loss of function of the erm(41) genes was associated with a T-to-C substitution at position 28 of the gene (T28C), leading to an amino acid change from Trp to Arg at codon 10. Pulmonary disease caused by M. abscessus subsp. abscessus strains with an nonfunctional erm(41) (C28 sequevar) may be responsive to macrolide-containing antibiotic regimens. Therefore, all M. abscessus subsp. abscessus strains with a functional erm(41) (T28 sequevar) were thought to be resistant to macrolide with extended incubation. Here, we report the first case of pulmonary disease caused by a strain of M. abscessus subsp. abscessus which was susceptible to macrolide due to T19 sequevar of erm(41) gene.
  
  
  
  A 62-year-old Korean female was referred to our hospital due to chronic cough, sputum, and hemoptysis lasting more than 5 months. The patient's sputum was positive for acid-fast bacilli staining and nontuberculous mycobacteria (NTM) were isolated twice from sputum specimens. The isolate was identified as M. abscessus subsp. abscessus. The isolate had a point mutation of C → T at position 19 (C19 → T) in the erm(41) gene, instead of expected C28 sequevar of erm(41), and had no rrl mutation. The isolate displayed a clarithromycin susceptible phenotype with an Arg → Stop codon change in erm(41). The patient was successfully treated with a macrolide-containing regimen.
  
  
  
  This is the first case of pulmonary disease caused by a strain of M. abscessus subsp. abscessus showing clarithromycin susceptible phenotype due to T19 sequevar of the erm(41) gene. The erm(41) gene is clinically important, and non-functional erm alleles may be an important issue for the management of MABC lung disease. The presence of a non-functional erm(41) allele in M. abscessus subsp. abscessus isolates may be associated with better outcomes.
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, 06351, South Korea.
authors.forename: Su-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
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, 06351, South Korea.
authors.forename: Byeong-Ho
authors.initials: BH
authors.lastname: Jeong
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, 06351, South Korea. wjkoh@skku.edu.
authors.forename: Won-Jung
authors.initials: WJ
authors.lastname: Koh
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D017291:Clarithromycin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000382:microbiology; D018942:Macrolides / Q000627:therapeutic use; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy* / Q000382:microbiology; D009170:Nontuberculous Mycobacteria / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D017354:Point Mutation
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D018942:Macrolides; D008780:Methyltransferases; C431709:ErmA protein, Bacteria; D017291:Clarithromycin
keywords: Clarithromycin; Drug resistance; Lung diseases; Mycobacterium abscessus; Nontuberculous mycobacteria