Factors related to response to intermittent treatment of Mycobacterium avium complex lung disease

Am J Respir Crit Care Med. 2006 Jun 1;173(11):1283-9. doi: 10.1164/rccm.200509-1531OC. Epub 2006 Mar 2.

Abstract

Rationale: Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multidrug therapy is difficult to tolerate.

Objectives: To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin.

Methods: A 1-yr prospective noncomparative trial of TIW treatment was conducted during 2000-2003 in 17 U.S. cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled IFN-gamma treatment. Improvement in sputum culture, high-resolution computed tomography (HRCT), and symptoms were assessed.

Results: Treatment response rates (and median response times) were 44% (2 mo or longer) for culture, 60% (5.5-11.5 mo) for HRCT, and 53% (8.5 mo) for symptoms. Having noncavitary, compared with cavitary, disease increased culture response by 4.0 times (95% confidence interval [CI], 1.7-9.2) and HRCT response by 4.9 times (95% CI, 1.9-13.0). Culture response was 1.5 times (95% CI, 1.1-2.2) higher for older subjects and 2.2 times (95% CI, 1.0-4.7) higher for previously untreated subjects. Being smear-negative increased culture response by 2.3 times (95% CI, 1.1-5.2) but decreased HRCT response by 4.4 times (95% CI, 1.7-11.5). Increasing ethambutol use by 5 mo increased culture response by 1.5 times (95% CI, 1.0-2.1) but decreased symptom response. Not having chronic obstructive pulmonary disease, bronchiectasis, or poor lung function increased symptom response by 1.9 to 3.9 times.

Conclusions: TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of chronic obstructive pulmonary disease, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / adverse effects
  • Bronchiectasis / drug therapy
  • Bronchiectasis / etiology
  • Clarithromycin / administration & dosage*
  • Clarithromycin / adverse effects
  • Double-Blind Method
  • Drug Therapy, Combination
  • Ethambutol / administration & dosage*
  • Ethambutol / adverse effects
  • Female
  • Forced Expiratory Flow Rates
  • Forced Expiratory Volume
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium avium Complex
  • Mycobacterium avium-intracellulare Infection / diagnostic imaging
  • Mycobacterium avium-intracellulare Infection / drug therapy*
  • Prospective Studies
  • Radiography
  • Rifampin / administration & dosage*
  • Rifampin / adverse effects
  • Sputum / microbiology
  • Treatment Outcome
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / microbiology

Substances

  • Antitubercular Agents
  • Ethambutol
  • Clarithromycin
  • Rifampin