Efficacy of clarithromycin and ethambutol for Mycobacterium avium complex pulmonary disease. A preliminary study

Ann Am Thorac Soc. 2014 Jan;11(1):23-9. doi: 10.1513/AnnalsATS.201308-266OC.


Rationale: Patients with Mycobacterium avium complex pulmonary disease are frequently administered a combination of clarithromycin, ethambutol, and rifampicin. However, rifampicin is known to reduce the serum levels of clarithromycin. It remains unclear whether a reduction in clarithromycin serum levels influences the clinical outcome of the Mycobacterium avium complex pulmonary disease treatment regimen.

Objectives: To compare a three-drug regimen (clarithromycin, ethambutol, and rifampicin) to a two-drug regimen (clarithromycin and ethambutol) for the treatment of Mycobacterium avium lung disease.

Methods: In a preliminary open-label study, we randomly assigned newly diagnosed, but as-yet untreated, patients with disease caused by Mycobacterium avium complex without HIV infection to either the three-drug or the two-drug regimen for 12 months. The primary endpoint was the conversion of sputum cultures to negative after 12 months of treatment. Patient data were analyzed using the intention-to-treat method.

Measurements and main results: Of 119 eligible patients, 59 were assigned to the three-drug regimen and 60 to the two-drug regimen. The rate of sputum culture conversion was 40.6% with the three-drug regimen and 55.0% with the two-drug regimen (difference, -14.4% [95% confidence interval, -32.1 to 3.4]). The incidence of adverse events leading to the discontinuation of treatment was 37.2 and 26.6% for the three-drug and the two-drug regimens, respectively.

Conclusions: This preliminary study suggests that treatment with clarithromycin and ethambutol is not inferior to treatment with clarithromycin, ethambutol, and rifampicin for Mycobacterium avium complex lung disease. Our findings justify a larger clinical trial to compare long-term clinical outcomes for the two treatment regimens. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000002819).

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / therapeutic use*
  • Antibiotics, Antitubercular / therapeutic use
  • Antitubercular Agents / therapeutic use*
  • Clarithromycin / therapeutic use*
  • Drug Therapy, Combination
  • Ethambutol / therapeutic use*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium avium Complex / isolation & purification
  • Mycobacterium avium-intracellulare Infection / drug therapy*
  • Rifampin / therapeutic use
  • Sputum / microbiology
  • Treatment Outcome
  • Tuberculosis, Pulmonary / drug therapy*


  • Anti-Bacterial Agents
  • Antibiotics, Antitubercular
  • Antitubercular Agents
  • Ethambutol
  • Clarithromycin
  • Rifampin