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

Abstract

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).

• Authors: Seiichi Miwa, Masahiro Shirai, Mikio Toyoshima, Toshihiro Shirai, Kazumasa Yasuda, Koshi Yokomura, Takashi Yamada, Masafumi Masuda, Naoki Inui, Kingo Chida, Takafumi Suda, Hiroshi Hayakawa
• Journal: Annals of the American Thoracic Society (Ann Am Thorac Soc) Vol. 11 Issue 1 Pg. 23-9 (Jan 2014) ISSN: 2325-6621 [Electronic] United States
• PMID: 24298907 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

• 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)