Activity of aztreonam in combination with avibactam, clavulanate, relebactam, and vaborbactam against multidrug resistant Stenotrophomonas maltophilia.

The objectives of this study were to evaluate and compare the in vitro activity and understand the mechanisms of resistance to aztreonam in combination with avibactam, clavulanate, relebactam, and vaborbactam against S. maltophilia. A panel of 47 clinical S. maltophilia strains non-susceptible to levofloxacin and/or trimethoprim-sulfamethoxazole were tested against each aztreonam-BLI combination via broth microdilution and 6 isolates were then evaluated in time-kill analyses. Three isolates with varying aztreonam-BLI MICs were subjected to whole-genome sequencing and quantitative reverse transcriptase polymerase chain reaction. Avibactam restored aztreonam susceptibility in 98% of aztreonam-resistant isolates, compared to 61%, 71%, and 15% with clavulanate, relebactam, and vaborbactam, respectively. The addition of avibactam to aztreonam resulted in a ≥2 log10 CFU/mL decrease at 24 hours vs. aztreonam alone against 5/6 isolates compared to 1/6 with clavulanate, 4/6 with relebactam, and 2/6 with vaborbactam. Molecular analyses revealed that decreased susceptibility to aztreonam-avibactam was associated with increased expression of genes encoding for L1, L2, and the efflux pump smeABC Aztreonam-avibactam is the most promising BLI-combination against multidrug resistant S. maltophilia. Decreased susceptibility may be due to the combination of overexpressed β-lactamases and efflux pumps. Further studies evaluating this combination against S. maltophilia are warranted. ...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research