Activity of the Novel Extended-spectrum β-Lactamase Inhibitor AAI101 in Combination with Cefepime Towards a Challenge Panel of Acinetobacter baumannii

Background AAI101 is a novel extended-spectrum β-lactamase inhibitor (BLI), active against ESBLs and a broad array of other BLs. AAI101 in combination with cefepime (FEP) is in Phase 2 development. Infections caused by A. baumannii, a pathogen endemic to the southern US and other global regions, are very challenging to treat, and often require combination therapy. This study examined the activity of FEP/AAI101 against a challenge set of A. baumannii clinical isolates enriched with OXA carbapenemase producers. Methods BLs in A. baumannii were identified by genotyping. Broth microdilution MICs and susceptibilities were obtained following CLSI methods and breakpoints (BPs), except for ceftazidime-avibactam (CAZ/AVI) where FDA P. aeruginosa BPs were used. CLSI FEP BPs were used for FEP/AAI101. Results All OXA-51 producers had the ISAba1 promoter. MIC90 data and % susceptibilities (%S) for FEP/AAI101 and comparators are shown in the Table: FEP/AAI101 was highly active against meropenem-susceptible (MPMs) isolates. FEP/AAI101 (AAI101 fixed at 8 µg/ml) covered 67% of OXA-51 and 53% of OXA-58 strains. Lower susceptibilities were obtained for OXA-23 and OXA-24/40 producers. FEP/AAI101 was the most active β-lactam product. Colistin (COL) was the only agent with consistently high activity against all A. baumannii isolates. Group FEP FEP/ AAI101 [4*] FEP/ AAI101 [8*] CAZ/ AVI [4*] AMP/ SUL [2:1*] PIP/ TAZ [4*] COL MPMs (N = 17) MIC90 64 8 0.06 64 32 256 1 %S 70.6 94.1 100 58.8 82.4 70.6 100 OXA-23 (N = 30) MIC90 >128 >128 >128 >128 128 >256 0.5 %S 3.3 0 0 96.7 OXA-24/40 (N = 30) MIC90 >128 >128 >128 64 128 >256 4 %S 3.3 3.3 6.7 6.7 3.3 0 86.7 OXA-51 (N = 30) MIC90 >128 >128 >128 >128 >128 >256 0.5 %S 0 36.7 66.7 3.3 16.7 0 100 OXA-58 (N = 30) MIC90 >128 128 64 >128 64 >256 1 %S 13.3 33.3 53.3 16.7 6.7 0 100 All (N = 137) MIC90 >128 >128 >128 >128 128 >256 1 %S 12.4 27.7 40.1 13.9 16.1 8.8 96.4 AMP, ampicillin; SUL, sulbactam; PIP, piperacillin; TAZ, tazobactam *BLI at fixed concentration in µg/mL or ratio as indicated Conclusion FEP/AAI101 was the most potent β-lactam product tested against clinical isolates of A. baumannii producing OXA-51 and OXA-58 β-lactamases. Infections by this difficult pathogen often require combination therapy, of which FEP-AAI101 may be a component. Disclosures S. Shapiro, Allecra: Employee, Salary