2443. Searching for the Optimal Treatment Regimen for Metallo-β-Lactamase Producing Enterobacteriaceae: Aztreonam Plus Ceftazidime–Avibactam vs. Aztreonam Plus Meropenem–Vaborbactam

BACKGROUND: Pathogens harboring metallo-β-lactamase (MBL) enzymes pose a large threat to public health. Aztreonam (ATM) is not hydrolyzed by MBLs but is inactivated by other β-lactamases, which are often co-harbored in MBL-producers. Ceftazidime/avibactam (CAZ/AVI) and meropenem/vaborbactam (MER/VBR) are novel β-lactam/β-lactamase inhibitors (BL/BLI) with potent activity against serine β-lactamase producing Enterobacteriaceae. Combining ATM with BL/BLI agents may provide activity against Enterobacteriaceae producing serine and MBLs. METHODS: Two clinical E. coli isolates were used. MICs were determined in triplicate and modal values are reported. Time kill analyses were performed in triplicate at standard inoculum (10(6)). Each agent was tested alone and in combination at either fCmax or ¼, ½, 1, 2, or 4× MIC based on susceptibility. Bactericidal activity was ≥3 log(10) reduction in CFU/mL from the starting inoculum. Synergy was ≥2 log(10) reduction in CFU/mL compared with the most active agent alone. Antagonism was ≥2 log(10) increase in CFU/mL compared with the most active agent alone. RESULTS: Genotypic/phenotypic susceptibilities are in Table 1. Against EC-1, ATM alone at fCmax had no activity. When combined with CAZ/AVI or MER/VBR, respectively, synergy was observed with average log(10) decrease in CFU/mL at 24 hours of 3.92 and 5.04 (Figure 1a). Synergy seemed to be driven solely by the addition of the BLI as ATM/CAZ and ATM/MER did not demonstrate synergy (Figure 1a). Against EC-2, ATM alone at 1/4× MIC showed no activity (Figure 1b). Combining ATM with either CAZ/AVI or MER/VBR did not improve the activity or demonstrate synergy (Figure 1b). Interestingly, removing CAZ significantly improved the activity of ATM/AVI. CONCLUSION: There were no significant differences in activity or synergy observed between the combinations of ATM with either CAZ/AVI or MER/VBR against serine- and MBL-producing E. coli. Synergy appears to be driven by the ATM-BLI combinations, with ATM-AVI demonstrating more consistent synergy than ATM-VBR. Further studies including more isolates and combinations are warranted. [Image: see text] [Image: see text] DISCLOSURES: E. Wenzler, Melinta Therapeutics: Speaker’s Bureau, Speaker honorarium.