Synergism of Rifabutin with Clarithromycin, Imipenem, and Tigecycline against the Complex.

Infections caused by the difficult-to-treat bacterium are increasing in frequency. Rifabutin, in contrast to rifampin, appears to be active against , especially against clarithromycin-resistant strains. However, explorations for potential synergy between rifabutin and available antimicrobials are currently limited. 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 rifabutin-based combination. The colony morphology was recorded. Molecular methods for determination of the subspecies and analysis of macrolide resistance were performed by sequencing of the , , (41), and genes. Rifabutin yielded an MIC of 16 mg/liter (range, 2 to 32 mg/liter) against 26 clinical isolates (comprising 13  subsp. and 13  subsp. isolates) and 5 reference strains, including subsp. ATCC 19977, subsp. BCRC 16915, subsp. BCRC 16916, ATCC 35752, and ATCC 700686. Significant synergism, classified by an FICI of ≤0.5, was demonstrated for the combinations of rifabutin and imipenem in 100% of subsp. and 69% of subsp. isolates, and significant synergism for rifabutin and tigecycline was demonstrated in 77% of subsp. and 69% of subsp. isolates. Among the 6 clarithromycin-resistant (MICs ≥ 8 mg/liter) subsp. isolates, the combination of rifabutin and clarithromycin was 100% synergistic. Rifabutin showed promising synergism with first-line anti- agents, especially for macrolide-resistant subsp. isolates.