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In Vitro Synergism of Rifabutin with Clarithromycin, Imipenem, and Tigecycline against the Mycobacterium abscessus Complex
- Source :
- Antimicrobial Agents and Chemotherapy. 63
- Publication Year :
- 2019
- Publisher :
- American Society for Microbiology, 2019.
-
Abstract
- 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 rifabutin-based 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 ≤0.5, 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 ≥ 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.
- Subjects :
- Pharmacology
0303 health sciences
Imipenem
Rifabutin
030306 microbiology
Tigecycline
Biology
Mycobacterium abscessus
bacterial infections and mycoses
rpoB
Antimicrobial
biology.organism_classification
In vitro
Microbiology
03 medical and health sciences
Infectious Diseases
Susceptibility
Clarithromycin
polycyclic compounds
medicine
bacteria
Pharmacology (medical)
030304 developmental biology
medicine.drug
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....f46227d13e733c3a667f3ebd55062719