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

Antimicrob Agents Chemother. 2017 Jan 24;61(2):e02189-16. doi: 10.1128/AAC.02189-16. Print 2017 Feb.

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.

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Female
  • Humans
  • Lung Diseases / microbiology*
  • Macrolides / pharmacology*
  • Macrolides / therapeutic use
  • Male
  • Middle Aged
  • Mycobacterium / drug effects*
  • Mycobacterium / pathogenicity
  • Mycobacterium Infections / drug therapy
  • Mycobacterium Infections / microbiology
  • Mycobacterium avium Complex / drug effects
  • Mycobacterium avium Complex / pathogenicity
  • Retrospective Studies
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Macrolides