In vitro synergism of rifabutin with clarithromycin, imipenem and tigecycline against the Mycobacterium abscessus complex [Susceptibility]

Background

Infections caused by the difficult-to-treat 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, exploring for potential synergy between rifabutin and available antimicrobials is currently limited.

Methods

In vitro synergism was evaluated by the checkerboard method for rifabutin and 10 antimicrobials in 31 mycobacterial strains. The fractional inhibitory concentration index (FICI) was calculated for each rifabutin-based combination. Colony morphology was recorded. Molecular subspeciation and macrolide resistance were determined by sequencing of the secA1, rpoB, hsp65, erm (41) and rrl genes.

Results

Rifabutin yielded an MIC₅₀ of 16 mg/L (range 2-32 mg/L) against 26 clinical M. abscessus isolates (comprising 13 M. abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense) 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 as classified by an FICI≤0.5 was demonstrated for the combinations of rifabutin and imipenem in 100% of M. abscessus subsp. abscessus vs. 69% of M. abscessus subsp. massiliense isolates, and for rifabutin and tigecycline in 77% of M. abscessus subsp. abscessus vs. 69% of M. abscessus subsp. massiliense isolates. Among the 6 clarithromycin resistant (MIC ≥8 mg/L) M. abscessus subsp. abscessus isolates, the combination of rifabutin and clarithromycin was 100% synergistic.

Conclusions

Rifabutin showed promising in vitro synergism with first-line anti-M. abscessus agents, especially for macrolide-resistant M. abscessus subsp. abscessus.

http://bit.ly/2Wbtsp9