Published ahead of print on March 2, 2006, doi:10.1164/rccm.200509-1531OC Am. J. Respir. Crit. Care Med., Volume 173, Number 11, June 2006, 1283-1289 A more recent version of this article appeared on June 1, 2006
Submitted on September 29, 2005 Factors Related to Response to Intermittent Treatment of Mycobacterium avium Complex Lung DiseasePhung K Lam1,1 Division of Pulmonary and Critical Care Medicine, University of California, San Diego, San Diego, CA, USA, 2 Department of Medicine, University of Texas Health Center, Tyler, TX, USA, 3 Division of Pulmonary and Critical Care Medicine and Internal Medicine, Mayo Clinic, Rochester, MN, USA, 4 Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, CA, USA, 5 Department of Medicine, New York University Medical Center/Bellevue Hospital, New York, NY, USA, 6 Divison of Mycobacterial and Respiratory Infections, National Jewish Medical and Research Center, Denver, CO, USA * To whom correspondence should be addressed. E-mail: acatanzaro{at}ucsd.edu.
Rationale: Mycobacterium avium complex pulmonary disease (MAC-PD) is associated with substantial morbidity, and standard daily multi-drug therapy is difficult to tolerate. Objectives: To characterize response to a three-times-weekly (TIW) regimen of clarithromycin, ethambutol, and rifampin. Methods: A 1-year prospective non-comparative trial of TIW treatment was conducted during 2000-2003 in 17 US cities. Participants were 91 HIV-negative adults, diagnosed with moderate to severe MAC-PD, who originally participated in a trial of an inhaled interferon-gamma treatment. Improvement in sputum culture, high-resolution computerized tomography (HRCT), and symptoms were assessed. Results: Treatment response rates (and median response times) were 44% (2 months or longer) for culture, 60% (5.5-11.5 months) for HRCT, and 53% (8.5 months) for symptoms. Having non-cavitary, compared to cavitary, disease increased culture response by 4.0 times (95% 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 months increased culture response by 1.5 times (95% CI: 1.0-2.1) but decreased symptom response. Not having COPD, bronchiectasis, or poor lung function increased symptom response by 1.9-3.9 times. Conclusions: TIW therapy was less effective for MAC-PD patients with cavitary disease and a history of COPD, bronchiectasis, or previous treatment for MAC-PD. Further research is needed to study the long-term outcomes of TIW treatment. Key words: Mycobacterium avium complex, clarithromycin, ethambutol, rifampin, risk factors
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