Macrolide-Resistant Mycobacterium avium Complex Lung Disease: Analysis of 102 Consecutive Cases

Ann Am Thorac Soc. 2016 Nov;13(11):1904-1911. doi: 10.1513/AnnalsATS.201604-246OC.

Abstract

Rationale: The management of macrolide-resistant Mycobacterium avium complex (MR-MAC) pulmonary disease is difficult and is thought to be analogous to that of multidrug-resistant tuberculosis (MDR-TB).

Objectives: This study aimed to clarify the cause of MR-MAC, to see how its management affected outcome, and to compare its prognosis with that of MDR-TB.

Methods: The medical records of 102 consecutive cases with MR-MAC pulmonary disease at three tertiary hospitals for mycobacteriosis in metropolitan Tokyo and one in Aichi prefecture from 2005 to 2014 were reviewed. The data of 311 consecutive cases with MDR-TB were extracted from the medical data at Fukujuji Hospital.

Measurements and main results: Of the 90 patients who met the criteria, 53 (58.9%) received inappropriate first-line treatment, and 28 (31.1%) deviated from the standard treatment because of the adverse effects of ethambutol. The survival rates for MR-MAC disease and MDR-TB were not significantly different (P = 0.6). Multivariate analysis showed that the combination of aminoglycoside and surgery resulted in the best treatment outcome (P = 0.02), although neither of the two factors reached significance by themselves. The continuation of clarithromycin and the addition of fluoroquinolones did not improve the outcome for the treatment of disease caused by MR-MAC.

Conclusions: Inappropriate prescription patterns and deviations from the standard treatment because of adverse drug reactions appeared to be the main causes of macrolide resistance in this patient series. Drug sensitivity testing should be performed at diagnosis to identify macrolide resistance and patients who may benefit from other therapy.

Keywords: clarithromycin; multidrug-resistant tuberculosis; prognosis; side effect.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Anti-Bacterial Agents / classification
  • Anti-Bacterial Agents / therapeutic use*
  • Clarithromycin / adverse effects
  • Ethambutol / adverse effects
  • Female
  • Humans
  • Inappropriate Prescribing / statistics & numerical data*
  • Japan
  • Kaplan-Meier Estimate
  • Logistic Models
  • Lung Diseases / drug therapy
  • Lung Diseases / microbiology
  • Macrolides / pharmacology*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mycobacterium avium Complex / drug effects
  • Mycobacterium avium-intracellulare Infection / drug therapy*
  • Tuberculosis, Multidrug-Resistant / drug therapy

Substances

  • Anti-Bacterial Agents
  • Macrolides
  • Ethambutol
  • Clarithromycin