Safety and Effectiveness of Clofazimine for Primary and Refractory Nontuberculous Mycobacterial Infection

Chest. 2017 Oct;152(4):800-809. doi: 10.1016/j.chest.2017.04.175. Epub 2017 May 5.

Abstract

Background: Clofazimine is an antimicrobial agent that has activity in vitro against mycobacteria. Increasingly, it has been used for the treatment of nontuberculous mycobacteria (NTM), despite limited data supporting its use in this setting. The objective of this study was to evaluate the safety, tolerability, and clinical outcomes associated with clofazimine in patients with NTM infection.

Methods: This observational-cohort study assessed clofazimine as used for pediatric and adult cystic fibrosis (CF) and non-CF patients with pulmonary and extrapulmonary NTM infection as part of a multidrug regimen from 2006 to 2014. Treatment regimens and adverse drug reactions (ADRs) were captured.

Results: A total of 112 patients were included (median age, 62 years); 24 patients (21%) had CF. Eighty-seven (78%) had refractory disease with failure of previous therapy. Fifty-four patients (48%) had Mycobacterium abscessus complex, 41 (37%) had Mycobacterium avium complex, and 16 (14%) had two NTM species. The median duration of clofazimine use was 383 days (range, 3-2,419 days). Sixteen patients (14%) stopped clofazimine due to an ADR after a median of 101 days (95% CI, 63-119). Forty-one of 82 patients (50%) with pulmonary disease converted to negative NTM cultures within 12 months.

Conclusions: Clofazimine was a safe, reasonably tolerated, and active oral drug for NTM infection in our heterogeneous population of pediatric and adult CF and non-CF patients. It should be considered as an alternative drug for treatment of NTM disease.

Keywords: Mycobacterium abscessus; Mycobacterium avium; clofazimine; cystic fibrosis; nontuberculous mycobacteria.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / administration & dosage
  • Child
  • Clofazimine / administration & dosage*
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium Infections, Nontuberculous / diagnosis
  • Mycobacterium Infections, Nontuberculous / drug therapy*
  • Mycobacterium Infections, Nontuberculous / microbiology
  • Nontuberculous Mycobacteria / isolation & purification*
  • Pneumonia / diagnosis
  • Pneumonia / drug therapy*
  • Pneumonia / microbiology
  • Radiography, Thoracic
  • Retrospective Studies
  • Sputum / microbiology*
  • Treatment Outcome
  • Young Adult

Substances

  • Anti-Inflammatory Agents
  • Clofazimine