P-1080. Aztreonam-Avibactam Activity Against Gram-negative Bacteria Isolated from Patients with Pneumonia from Europe, Asia, and Latin America (2021–2023)

Abstract Background Aztreonam-avibactam (ATM-AVI) is under development to treat Gram-negative (GN) infections. We evaluated the antimicrobial susceptibility of GN bacilli causing pneumonia Activity of β-lactamase inhibitor combinations Methods 7,560 organisms were consecutively collected (1/patient) from patients with pneumonia in 59 medical centres located in Western Europe (W-EU; 10 countries; 24 centres; 3,977 isolates), Eastern Europe (E-EU; 9 countries; 15 centres; 1,617 isolates), the Asia-Pacific region (APAC; 7 countries; 12 centres; 1,238 isolates), and Latin America (LATAM; 6 countries; 8 centres; 728 isolates). Isolates were susceptibility tested by broth microdilution. Cefiderocol was only tested against carbapenem-resistant Enterobacterales (CRE). CLSI breakpoints were applied. An ATM-AVI PK/PD susceptible (S) breakpoint of ≤8 mg/L was applied for comparison. CREs were screened for carbapenemase-encoding genes by whole genome sequencing. Results ATM-AVI inhibited >99.9% of Enterobacterales (ENT) at ≤8 mg/L (MIC50/90, 0.06/0.25 mg/L) and showed consistent activity across regions (Table). Only 2 ENT had an ATM-AVI MIC >8 mg/L, an E. cloacae (Italy) and a K. pneumoniae (Taiwan). CRE rates ranged from 1.3% (W-EU) to 20.5% (LATAM). Multidrug-resistance (MDR; non-S to ≥3 classes) rates varied from 20.2% (W-EU) to 47.2% (LATAM). ATM-AVI retained potent activity against CRE (MIC50/90, 0.25/0.5 mg/L; 99.7% inhibited at ≤8 mg/L) and MDR ENT (MIC50/90, 0.12/0.5 mg/L; 99.9% inhibited at ≤8 mg/L). Cefiderocol was active against 95.8% of CRE. Ceftazidime-avibactam (CAZ-AVI; 61.7% S), meropenem-vaborbactam (MEM-VAB; 52.8%S), and imipenem-relebactam (IMI-REL; 44.5% S) showed limited activity against CRE and S rates varied greatly among regions. A metallo-β-lactamase was identified in 35.8% of CREs, varying from 23.8% in LATAM to 60.3% in APAC. IMI-REL (95.3% S), CAZ-AVI (94.7% S), and ceftolozane-tazobactam (TOL-TAZ; 93.3% S) were the most active agents against P. aeruginosa; whereas ATM-AVI inhibited 79.5% of isolates at ≤8 mg/L and 76.1% were piperacillin-tazobactam (PIP-TAZ)-S. ATM-AVI inhibited 98.9% of S. maltophilia isolates (n=440) at ≤8 mg/L. Conclusion ATM-AVI was the most active compound against CRE and S. maltophilia isolated from patients with pneumonia. Disclosures Marisa Winkler, MD, PhD, Element Iowa City (JMI Laboratories) was contracted to perform services in 2023 for > 30 biotech and pharmaceutical companies: Grant/Research Support Rodrigo E. Mendes, PhD, GSK: Grant/Research Support