Short Course Antimicrobial Therapy for Adult Patients with Mycobacterium Avium Complex (MAC) Pulmonary Infection: A Pilot Study

Abstract

Rationale: Patients with pulmonary infections due to Mycobacterium avium complex (MAC) are treated with multiple antimicrobial agents administered simultaneously for a period of at least one year after conversion of sputum cultures from positive to negative. However, this therapy is often poorly tolerated. Additionally, repeat infections upon discontinuation of therapy commonly occur and often necessitate subsequent prolonged courses of therapy. Shorter courses of drug therapy would likely diminish the morbidity of treatment but could potentially result in the development of antibiotic resistance. We hypothesized that a 3 months course of antimicrobial therapy for MAC would not induce macrolide resistance and be well tolerated, while providing clinical benefit to patients. This pilot study was conducted to test this hypothesis in a small number of patients. Methods: We treated adults with MAC pulmonary disease associated with multifocal bronchiectasis and multiple small nodules with a 3 months course of triple antibiotic therapy including a macrolide antibiotic (clarithromycin or azithromycin). The development of macrolide resistance was the primary outcome assessed. Secondary outcomes included drug tolerability, quality of life (QOL) assessments, and temporal changes in pulmonary function tests (PFT) and high resolution computerized tomography (HRCT) scans. Measurements and main results: Thirteen adult patients with MAC pulmonary infection were recruited and begun on antimicrobial therapy; 12 completed 3 months of treatment; 11 had 6 month follow-up. No participant developed evidence of macrolide resistant MAC. HRCT findings at 6 months were stable or improved relative to baseline in most participants (8/11 and 9/11, respectively). The symptom score on the St. George Respiratory Questionnaire (SGRQ) improved at the conclusion of drug administration at 3 months in 10 of 12 patients and there was improvement on the mental subscale of the SF-12 at 6 months. Conclusions: We demonstrated preliminary supporting evidence that a 3 months course of triple drug therapy in adult patients with MAC pulmonary infections does not induce macrolide resistance and that it may be associated with improved QOL and radiographic stability. Implications: A three month course of multiple drug therapy for patients with MAC pulmonary infections may offer an alternative to standard prolonged drug therapy. Subsequent periodic, short courses of therapy may be needed if re-infection occurs.