Clinical Characteristics and Treatment Outcomes of Patients with Acquired Macrolide-resistant Mycobacterium abscessus Lung Disease [PublishAheadOfPrint]

Macrolide antibiotics are mainstays in the treatment of lung disease due to the Mycobacterium abscessus complex. Although previous studies have reported development of acquired macrolide resistance in this species, limited data are available on the outcomes of lung disease due to macrolide-resistant M. abscessus subspecies abscessus (hereafter M. abscessus). This study evaluated the clinical features, treatment outcomes, and molecular characteristics of macrolide-resistant isolates of M. abscessus. We performed a retrospective review of medical records and genetic analysis of clinical isolates from 13 patients who had acquired macrolide-resistant M. abscessus lung disease between November 2006 and March 2016. Eleven (85%) patients had the nodular bronchiectatic form, and two (15%) patients had the fibrocavitary form of the disease. When acquired macrolide resistance was detected, 10 (77%) patients were on antibiotic therapy for M. abscessus, and three (23%) patients were on therapy for lung disease due to other nontuberculous mycobacteria. The median treatment duration after detecting resistance was 24.0 months (interquartile range: 16.0--43.0 months). Treatment outcomes were poor, and final sputum culture conversion was achieved in only one (8%) patient, after resectional surgery. All 13 clinical isolates demonstrated point mutations at positions 2058 (n = 10) or 2059 (n = 3) of the 23S rRNA gene, which resulted in acquired macrolide resistance. This study indicates that treatment outcomes are very poor after the development of acquired macrolide resistance in patients with M. abscessus lung disease. Thus, more effective measures are needed to prevent development and effectively treat macrolide-resistant M. abscessus lung disease.

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