P1158 Evaluation of -based combination therapies for NDM- producing Enterobacteriaceae: aztreonam plus - vs. aztreonam plus -vaborbactam Mark Biagi*1, Tiffany Wu1, Michelle Lee1, Eric Wenzler1

1 Pharmacy Practice, University of Illinois at Chicago, Chicago, United States Background: Metallo-β-lactamase-(MBL) producing Enterobacteriaceae are capable of hydrolyzing all β-lactams with the exception of aztreonam (ATM), although these pathogens often co-harbor β-lactamases rendering ATM ineffective as monotherapy. Combining ATM with novel β-lactam/β-lactamase inhibitors, such as ceftazidime-avibactam (CAZ-AVI) or meropenem-vaborbactam (MER-VAB), may restore ATM’s activity and provide clinicians new options for Enterobacteriaceae co-producing serine and MBLs. Materials/methods: Two clinical Escherichia coli isolates were used for all experiments. Isolate EC-1 produced NDM and TEM and isolate EC-2 produced NDM, CMY-2/FOX, CTX-M-1, OXA-48, and TEM. MICs were determined in triplicate and modal values are reported. Time kill analyses were performed in triplicate at standard inoculum (106). Individual β-lactams were tested at the lesser of ¼, ½, 1, 2, and 4x the MIC or free peak concentration (fCmax). Combinations employed the highest concentration of each β-lactam alone that showed no meaningful activity (≤1 log10 CFU/mL decrease from the starting inoculum) compared to the drug-free control strain. Bactericidal activity was ≥3 log10 reduction in CFU/mL from the starting inoculum. Synergy was ≥2 log10 reduction in CFU/mL compared to the most active agent alone. Results: Both isolates were resistant to all commercially available agents tested. ATM alone displayed no activity against EC-1 (≤1x MIC) or EC-2 (fCmax), respectively (Figure 1). The addition of either CAZ/AVI or MER-VAB was synergistic against both isolates and resulted in no observable growth at 24 hours. Synergy was observed for ATM/MER against EC-1 only and no synergy was observed for ATM/CAZ against either isolate. Conclusions: There were no significant differences in activity or synergy observed between the combinations of ATM with either CAZ-AVI or MER-VAB against MBL and serine ß-lactamase producing E. coli. Synergy appears to be primarily driven by the ATM-β-lactamase inhibitor interaction rather than the dual β-lactam interaction. Further studies including more isolates and combinations are warranted.

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