title: Clinical Characteristics, Treatment Outcomes, and Resistance Mutations Associated with Macrolide-Resistant Mycobacterium avium Complex Lung Disease.
abstract: Macrolide antibiotics are key components of the multidrug treatment regimen for treating lung disease (LD) due to Mycobacterium avium complex (MAC). Despite the emergence of macrolide resistance, limited data are available on macrolide-resistant MAC-LD. This study evaluated the clinical features and treatment outcomes of patients with macrolide-resistant MAC-LD and the molecular characteristics of the macrolide-resistant isolates. A retrospective review of the medical records of 34 patients with macrolide-resistant MAC-LD who were diagnosed between January 2002 and December 2014 was performed, along with genetic analysis of 28 clinical isolates. Nineteen (56%) patients had the fibrocavitary form of MAC-LD, and 15 (44%) had the nodular bronchiectatic form. M. intracellulare was the etiologic organism in 21 (62%) patients. Approximately two-thirds (22/34 [65%]) of the patients had been treated with currently recommended multidrug regimens that included macrolide, ethambutol, and rifamycin prior to the emergence of macrolide resistance, and none had been treated with macrolide monotherapy. The median duration of treatment after the detection of macrolide resistance was 23.0 months (interquartile range, 16.8 to 45.3 months). Treatment outcomes were poor after the development of macrolide resistance, with favorable treatment outcomes achieved in only five (15%) patients, including two patients who underwent surgical resection. One-, 3-, and 5-year mortality rates were 9, 24, and 47%, respectively. Molecular analysis of 28 clinical isolates revealed that 96% (27/28) had point mutations at position 2058 or 2059 of the 23S rRNA gene. Our analyses indicate that more effective therapy is needed to treat macrolide-resistant MAC-LD and prevent its development.
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Seong Mi
authors: SM
authors: Moon
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Hye Yun
authors: HY
authors: Park
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Su-Young
authors: SY
authors: Kim
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Byung Woo
authors: BW
authors: Jhun
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Hyun
authors: H
authors: Lee
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Kyeongman
authors: K
authors: Jeon
authors: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Dae Hun
authors: DH
authors: Kim
authors: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Hee Jae
authors: HJ
authors: Huh
authors: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Chang-Seok
authors: CS
authors: Ki
authors: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Nam Yong
authors: NY
authors: Lee
authors: Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Hong Kwan
authors: HK
authors: Kim
authors: Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Yong Soo
authors: YS
authors: Choi
authors: Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Jhingook
authors: J
authors: Kim
authors: Korean Institute of Tuberculosis, Cheongju, South Korea.
authors: Seung-Heon
authors: SH
authors: Lee
authors: Korean Institute of Tuberculosis, Cheongju, South Korea.
authors: Chang Ki
authors: CK
authors: Kim
authors: Department of Microbiology, Yonsei University College of Medicine, Seoul, South Korea.
authors: Sung Jae
authors: SJ
authors: Shin
authors: Division of Mycobacterial and Respiratory Infections, Department of Medicine, National Jewish Health, Denver, Colorado, USA.
authors: Charles L
authors: CL
authors: Daley
authors: 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: Won-Jung
authors: WJ
authors: Koh
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D005798:Genes, Bacterial; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D018942:Macrolides / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D012189:Retrospective Studies; D012293:Rifampin / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D018942:Macrolides; D012338:RNA, Ribosomal, 23S; D004977:Ethambutol; D012293:Rifampin