Abstract
BACKGROUND: Aztreonam-avibactam (ATM-AVI) was recently approved by the United States (US) Food and Drug Administration (FDA) for the treatment of intra-abdominal infections. ATM-AVI has shown potent activity against multidrug-resistant (MDR) Enterobacterales, including metallo-β-lactamase (MBL) producers. We evaluated the antimicrobial susceptibility of Enterobacterales and P. aeruginosa (PSA) of immunosuppressed patients from US medical centers. [Figure: see text] [Figure: see text] METHODS: Bacterial isolates were consecutively collected (1/patient) from 75 US medical centers in 2019-2024 and susceptibility tested by broth microdilution. Enterobacterales and PSA from patients hospitalized in hematology, oncology, and transplant units were evaluated. Carbapenem-resistant Enterobacterales (CRE; isolates with MIC ≥ 4 mg/L for meropenem and/or imipenem) were screened for β-lactamase by whole genome sequencing. RESULTS: Enterobacterales were mainly from bloodstream infection (BSI; 53.6%) and urinary tract infection (UTI; 19.9%) and PSA were mainly from BSI (37.9%) and pneumonia (35.0%). ATM-AVI, ceftazidime-avibactam (CAZ-AVI), and meropenem-vaborbactam (MEM-VAB) were highly active against Enterobacterales (99.9-99.4% susceptible [S]), including MDR isolates (99.6-98.1% S; Table 1), ATM-AVI retained potent activity against CRE isolates (95.8% S). Ceftolozane-tazobactam (TOL-TAZ) showed good activity against E. coli (95.7% S), and K. pneumoniae (92.8% S), but limited activity against E. cloacae species complex (75.9% S; Table 2). All (100.0%) carbapenemase (CBase)-producing CRE isolates were ATM-AVI-S while 77.4% were CAZ-AVI-S and 67.7% were MEM-VAB-S. The most common CBases were KPC (61.3%), NDM (16.1%), and OXA-48 types (16.1%). MBL represented 19.4% of CBases. The most active agents against PSA were CAZ-AVI (95.7% S), TOL-TAZ (94.8% S), and tobramycin (91.5% S). PIP-TAZ and meropenem were active against 81.4% and 82.5% of PSA, respectively, and ATM-AVI inhibited 78.6% of PSA at ≤8 mg/L. CONCLUSION: ATM-AVI demonstrated almost complete activity (99.9% S) against Enterobacterales, including 100.0% of CBase producers, and both CAZ-AVI and TOL-TAZ were highly active against PSA from immunosuppressed patients. DISCLOSURES: Helio Sader, United States Food and Drug Administration: FDA Contract Number: 75F40123C00140 Mariana Castanheira, PhD, Melinta Therapeutics: Advisor/Consultant|Melinta Therapeutics: Grant/Research Support Rodrigo E. Mendes, PhD, GSK: Grant/Research Support|Shionogi & Co., Ltd.: Grant/Research Support|United States Food and Drug Administration: FDA Contract Number: 75F40123C00140