Macrolide resistant Mycobacterium avium complex pulmonary disease following clarithromycin and ethambutol combination therapy

Respir Med. 2020 Aug:169:106025. doi: 10.1016/j.rmed.2020.106025. Epub 2020 May 15.

Abstract

Rationale: Whether two-drug therapy (clarithromycin and ethambutol) for Mycobacterium avium complex (MAC) pulmonary disease contributes to the development of macrolide-resistant MAC is unclear.

Objective: To compare the incidence of macrolide-resistant MAC between patients treated with two-drug therapy (clarithromycin and ethambutol) and the standard three-drug therapy (clarithromycin, ethambutol, and rifampicin) for MAC pulmonary disease.

Methods: We retrospectively reviewed 147 patients with treatment-naive MAC pulmonary disease who had received two-drug therapy (n = 47) or three-drug therapy (n = 100) between 1997 and 2016 at National Hospital Organization, Tenryu Hospital, Hamamatsu, Japan. The risk of development of macrolide-resistant MAC was evaluated by calculating the cumulative incidence rate using Gray's test.

Results: The median follow-up period was 74.5 months. During the follow-up period, one of the 47 patients (2.1%) in the two-drug group developed macrolide-resistant MAC, compared to 12 of the 100 patients (12.0%) in the three-drug group. The cumulative incidence rate of macrolide-resistant MAC was lower in the two-drug group than in the three-drug group (0.0023; 95% confidence interval, 0.002 to 0.107 versus 0.200; 95% confidence interval, 0.100 to 0.324, p = 0.0593).

Conclusions: These results suggest that two-drug treatment with clarithromycin and ethambutol for MAC pulmonary disease does not lead to a higher incidence of resistance acquisition to clarithromycin than the standard three-drug treatment.

Keywords: Antibiotic resistance; Clarithromycin; Mycobacterium avium-intracellulare complex.

MeSH terms

  • Aged
  • Anti-Bacterial Agents / pharmacology*
  • Clarithromycin / adverse effects
  • Clarithromycin / therapeutic use*
  • Drug Resistance, Bacterial*
  • Drug Therapy, Combination
  • Ethambutol / adverse effects
  • Ethambutol / therapeutic use*
  • Female
  • Humans
  • Incidence
  • Japan / epidemiology
  • Macrolides / pharmacology*
  • Male
  • Middle Aged
  • Mycobacterium avium Complex / drug effects*
  • Mycobacterium avium-intracellulare Infection*
  • Negative Results*
  • Pneumonia, Bacterial / drug therapy*
  • Pneumonia, Bacterial / epidemiology
  • Pneumonia, Bacterial / microbiology*
  • Rifampin / adverse effects
  • Rifampin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Macrolides
  • Ethambutol
  • Clarithromycin
  • Rifampin