title: Clinical Characteristics and Treatment Outcomes of Patients with Macrolide-Resistant Mycobacterium massiliense Lung Disease.
abstract: Macrolide antibiotics are cornerstones in the treatment of Mycobacterium massiliense lung disease. Despite the emergence of resistance, limited data on macrolide-resistant M massiliense lung disease are available. This study evaluated the clinical features and treatment outcomes of patients and the molecular characteristics of macrolide-resistant M massiliense isolates. We performed a retrospective review of medical records and genetic analyses of clinical isolates from 15 patients who had macrolide-resistant M massiliense lung disease between September 2005 and February 2015. Nine patients (60%) had the nodular bronchiectatic form of the disease, and six (40%) had the fibrocavitary form. Before the detection of macrolide resistance, three patients (20%) were treated with macrolide monotherapy, four (27%) with therapy for presumed Mycobacterium avium complex infections, and eight (53%) with combination antibiotic therapy for M massiliense lung disease. The median treatment duration after the detection of resistance was 18.7 months (interquartile range, 11.2 to 39.8 months). Treatment outcomes were poor, with a favorable outcome being achieved for only one patient (7%), who underwent surgery in addition to antibiotic therapy. The 1-, 3-, and 5-year mortality rates were 7, 13, and 33%, respectively. Of the 15 clinical isolates, 14 (93%) had point mutations at position 2058 (n = 9) or 2059 (n = 5) of the 23S rRNA gene, resulting in macrolide resistance. Our study indicates that treatment outcomes are poor and mortality rates are high after the development of macrolide resistance in patients with M massiliense lung disease. Thus, preventing the development of macrolide resistance should be a key consideration during treatment.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hayoung
authors.initials: H
authors.lastname: Choi
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Su-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Jhun
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hye Yun
authors.initials: HY
authors.lastname: Park
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Kyeongman
authors.initials: K
authors.lastname: Jeon
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Dae Hun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Huh
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Nam Yong
authors.initials: NY
authors.lastname: Lee
authors.affiliation: Korean Institute of Tuberculosis, Cheongju, South Korea.
authors.forename: Seung-Heon
authors.initials: SH
authors.lastname: Lee
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 Mycobacterial and Respiratory Infections, Department of Medicine, National Jewish Health, Denver, Colorado, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Daley
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea wjkoh@skku.edu.
authors.forename: Won-Jung
authors.initials: WJ
authors.lastname: Koh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000382:microbiology*; D018942:Macrolides / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000187:drug effects* / Q000472:pathogenicity; D009164:Mycobacterium Infections / Q000188:drug therapy / Q000382:microbiology; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000472:pathogenicity; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides
keywords: Mycobacterium massiliense; drug resistance; macrolides; nontuberculous mycobacteria