OR25

1:Inserm U1070 PHAR2, Pharmacology of Antimicrobial Agents and Antibioresistance; 2:Laboratory of Toxicolgy and Pharmacokinetic, Poitiers University Hospital

Mycobacterium abscessus (Mabs), an opportunistic pathogen, is associated with severe pulmonary outcomes in susceptible population like cystic fibrosis patients. Treatment requires prolonged multidrug regimens (12–18 months) with cure rates below 30%, largely due to intrinsic resistance mechanisms and limited effective antimicrobials. Recently, fidaxomicin—a macrocyclic antibiotic approved for Clostridium difficile infections— was identified as a potential candidate against Mabs ¹. In this study, we assessed the antimicrobial activity of fidaxomicin against Mabs and explore its interaction with six commonly used antibiotics.

The minimal inhibitory concentration (MIC) of fidaxomicin was determined against M. abscessus ATCC 19977T reference strain using the broth microdilution method in Middlebrook 7H09 medium (10% OADC and 0.5% glycerol) (n=4). Results were read after 3 days of incubation at 35 ± 2 °C. Synergistic activity between fidaxomicin and azithromycin, amikacin, apramycin, imipenem, linezolid, or tigecycline was evaluated using the checkerboard method (n=3). The efficacy of each combination was quantified by calculating the Fractional Inhibitory Concentration Index (FICI), with synergy defined as minimal FICI ≤ 0.5.

The MIC of fidaxomicin was 8 -16 mg/L. Fidaxomicin combined with azithromycin showed a synergistic effect (minimal FICI= 0.375) as well as with imipenem and tigecycline (minimal FICI of 0.375 and 0.5 respectively). No synergistic interaction was found with combination of fidaxomicin with either amikacin, apramycin or linezolid (minimal FICI > 0.5).

The synergistic association of fidaxomicin with azithromycin, imipenem or tigecycline is highlighting the potential of fidaxomicin as a valuable component of combination therapy.

1.            Sun, Q. et al. J. Med. Microbiol. 71, (2022).