Infections caused by the difficult-to-treat bacterium Mycobacterium abscessus are increasing in frequency. Rifabutin, in contrast to rifampin, appears to be active in vitro against M. abscessus, especially against clarithromycin-resistant strains. However, explorations for potential synergy between rifabutin and available antimicrobials are currently limited. In vitro synergism between rifabutin and 10 antimicrobials was evaluated in 31 mycobacterial strains by the checkerboard method. The fractional inhibitory concentration index (FICI) was calculated for each rifabutinbased combination. The colony morphology was recorded. Molecular methods for determination of the M. abscessus subspecies and analysis of macrolide resistance were performed by sequencing of the secA1, rpoB, hsp65, erm (41), and rrl genes. Rifabutin yielded an MIC 50 of 16 mg/liter (range, 2 to 32 mg/liter) against 26 clinical M. abscessus isolates (comprising 13 M. abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates) and 5 reference strains, including M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii BCRC 16915, M. abscessus subsp. massiliense BCRC 16916, M. chelonae ATCC 35752, and M. peregrinum ATCC 700686. Significant synergism, classified by an FICI of Յ0.5, was demonstrated for the combinations of rifabutin and imipenem in 100% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates, and significant synergism for rifabutin and tigecycline was demonstrated in 77% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates. Among the 6 clarithromycin-resistant (MICs Ն 8 mg/liter) M. abscessus subsp. abscessus isolates, the combination of rifabutin and clarithromycin was 100% synergistic. Rifabutin showed promising in vitro synergism with first-line anti-M. abscessus agents, especially for macrolide-resistant M. abscessus subsp. abscessus isolates.

BackgroundMycobacterium abscessus (MAB) has emerged as the predominant pulmonary non-tuberculous mycobacterial pathogen in parts of Asia, including Taiwan. The reasons for the significant increase in MAB infections in the non-cystic fibrosis (CF) populations are poorly understood. The study aimed to elucidate whether this increase is related to the spread of the globally successful clone of MAB.MethodsWe performed multilocus sequence typing of 371 nonduplicated MAB pulmonary isolates from 371 patients sampled between 2010–2017 at seven hospitals across Taiwan.ResultsIn total, 183 (49.3%) isolates were M. abscessus subsp. abscessus (MAB-a), 187 (50.4%) were M. abscessus subsp. massiliense (MAB-m), and 1 (0.3%) was M. abscessus subsp. bolletii (MAB-b). MAB-a sequence type (ST)1 (23.7%) and ST127 (3.8%), followed by MAB-m ST48 (16.2%), ST117 (15.1%), ST23 (8.6%) were most common overall. Of MAB-a strains, 50 (27.3%) belonged to novel STs and 38 (10.2%) were singleton strains, while of MAB-m strains, only 10 (5.3%) were novel and 8 (2.2%) were singletons. From 2010 to 2017, the frequency of the historically dominant ST1 declined from 28.6% to 22.5%, whereas the recently emerged globally successful clonal cluster 3, ST23 and ST48, increased from 14.3% to 40.0%.ConclusionsThe dominance of ST1 particularly in the last 2 years of this study appears to be declining, while ST23, reported in outbreaks among CF and post-surgical cohorts across the Americas and Europe, alongside the closely related ST48, is present among non-CF populations in Taiwan. These trends need to be confirmed with further ongoing studies to track the molecular epidemiology of clinical MAB isolates worldwide.