First line treatment selection modifies disease course and long-term clinical outcomes in Mycobacterium avium complex pulmonary disease

• Published in: Scientific reports Vol. 11; no. 1; pp. 1178 - 10
• Main Authors: Fukushima, Kiyoharu, Kitada, Seigo, Komukai, Sho, Kuge, Tomoki, Matsuki, Takanori, Kagawa, Hiroyuki, Tsujino, Kazuyuki, Miki, Mari, Miki, Keisuke, Kida, Hiroshi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/326; 692/308; 692/499; 692/700; Aged; Anti-Bacterial Agents - therapeutic use; Antitubercular Agents - therapeutic use; Body mass index; C-reactive protein; Clarithromycin; Clinical outcomes; Diabetes mellitus; Disease Progression; Drug Therapy, Combination - methods; Ethambutol; Female; Fluoroquinolones; Heterogeneity; Humanities and Social Sciences; Humans; Lung diseases; Lung Diseases - drug therapy; Lung Diseases - microbiology; Male; Mortality; multidisciplinary; Mycobacterium avium; Mycobacterium avium Complex - drug effects; Mycobacterium avium-intracellulare Infection - drug therapy; Mycobacterium avium-intracellulare Infection - microbiology; Patients; Regression analysis; Retrospective Studies; Rifamycins; Science; Science (multidisciplinary); Sputum; Sputum - microbiology; Tuberculosis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-81025-w

The combination of rifamycin (RFP), ethambutol (EB), and macrolides is currently the standard regimen for treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). However, poor adherence to the standardized regimens recommended by current guidelines have been reported. We undertook a single-centred retrospective cohort study to evaluate the long-term outcomes in 295 patients with MAC-PD following first line treatment with standard (RFP, EB, clarithromycin [CAM]) or alternative (EB and CAM with or without fluoroquinolones (FQs) or RFP, CAM, and FQs) regimens. In this cohort, 80.7% were treated with standard regimens and 19.3% were treated with alternative regimens. After heterogeneity was statistically corrected using propensity scores, outcomes were superior in patients treated with standard regimens. Furthermore, alternative regimens were significantly and independently associated with sputum non-conversion, treatment failure and emergence of CAM resistance. Multivariate cox regression analysis revealed that older age, male, old tuberculosis, diabetes mellitus, higher C-reactive protein, and cavity were positively associated with mortality, while higher body mass index and M. avium infection were negatively associated with mortality. These data suggest that, although different combination regimens are not associated with mortality, first line administration of a standard RFP + EB + macrolide regimen offers the best chance of preventing disease progression in MAC-PD patients.