Clinical Characteristics and Treatment Outcomes of Patients with Acquired Macrolide-Resistant Mycobacterium abscessus Lung Disease

Antimicrob Agents Chemother. 2017 Sep 22;61(10):e01146-17. doi: 10.1128/AAC.01146-17. Print 2017 Oct.

Abstract

Macrolide antibiotics are mainstays in the treatment of lung disease due to the Mycobacterium abscessus complex. Although previous studies have reported development of acquired macrolide resistance in this species, limited data are available on the outcomes of lung disease due to macrolide-resistant Mycobacterium abscessus subsp. abscessus This study evaluated the clinical features, treatment outcomes, and molecular characteristics of macrolide-resistant isolates of M. abscessus subsp. abscessus We performed a retrospective review of medical records and genetic analysis of clinical isolates from 13 patients who had acquired macrolide-resistant M. abscessus subsp. abscessus lung disease between November 2006 and March 2016. Eleven (85%) patients had the nodular bronchiectatic form of the disease, and two (15%) patients had the fibrocavitary form. When acquired macrolide resistance was detected, 10 (77%) patients were on antibiotic therapy for M. abscessus subsp. abscessus, and three (23%) patients were on therapy for lung disease due to other nontuberculous mycobacteria. The median treatment duration after detecting resistance was 24.0 months (interquartile range, 16.0 to 43.0 months). Treatment outcomes were poor, and final sputum culture conversion was achieved in only one (8%) patient, after resectional surgery. All 13 clinical isolates demonstrated point mutations at position 2058 (n = 10) or 2059 (n = 3) of the 23S rRNA gene, which resulted in acquired macrolide resistance. This study indicates that treatment outcomes are very poor after the development of acquired macrolide resistance in patients with M. abscessus subsp. abscessus lung disease. Thus, more effective measures are needed to prevent development and effectively treat macrolide-resistant M. abscessus subsp. abscessus lung disease.

Keywords: Mycobacterium abscessus; drug resistance; macrolides; nontuberculous mycobacteria.

MeSH terms

  • Aged
  • Anti-Bacterial Agents / therapeutic use*
  • Drug Resistance, Bacterial / genetics*
  • Female
  • Humans
  • Lung Diseases / drug therapy*
  • Lung Diseases / microbiology
  • Macrolides / therapeutic use*
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mycobacterium Infections, Nontuberculous / drug therapy*
  • Mycobacterium abscessus / drug effects*
  • Mycobacterium abscessus / genetics
  • Retrospective Studies
  • Sputum / microbiology
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Macrolides