Clinical characteristics, treatment outcomes, and resistance mutations associated with macrolide-resistant mycobacterium avium complex lung disease

Seong Mi Moon, Hye Yun Park, Su Young Kim, Byung Woo Jhun, Hyun Lee, Kyeongman Jeon, Dae Hun Kim, Hee Jae Huh, Chang Seok Ki, Nam Yong Lee, Hong Kwan Kim, Yong Soo Choi, Jhingook Kim, Seung Heon Lee, Chang Ki Kim, Sung Jae Shin, Charles L. Daley, Won Jung Koh

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6758-6765
Number of pages8
JournalAntimicrobial agents and chemotherapy
Volume60
Issue number11
DOIs
Publication statusPublished - 2016 Nov

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Moon, S. M., Park, H. Y., Kim, S. Y., Jhun, B. W., Lee, H., Jeon, K., Kim, D. H., Huh, H. J., Ki, C. S., Lee, N. Y., Kim, H. K., Choi, Y. S., Kim, J., Lee, S. H., Kim, C. K., Shin, S. J., Daley, C. L., & Koh, W. J. (2016). Clinical characteristics, treatment outcomes, and resistance mutations associated with macrolide-resistant mycobacterium avium complex lung disease. Antimicrobial agents and chemotherapy, 60(11), 6758-6765. https://doi.org/10.1128/AAC.01240-16