P-1315. Activity of Aztreonam-avibactam and Ceftazidime-Avibactam against Enterobacterales and Pseudomonas aeruginosa Causing Infections in Immunosuppressed Patients from United States Medical Centers (2019-2024)

TL;DR

This study evaluates how well new antibiotics work against drug-resistant bacteria in immunosuppressed patients in U.S. hospitals.

Contribution

The study provides new data on the effectiveness of aztreonam-avibactam and other antibiotics against multidrug-resistant bacteria in immunocompromised patients.

Findings

Aztreonam-avibactam showed 99.9% susceptibility against Enterobacterales, including all carbapenemase-producing isolates.

Ceftazidime-avibactam and ceftolozane-tazobactam were highly effective against Pseudomonas aeruginosa.

Meropenem-vaborbactam had lower efficacy against carbapenemase-producing Enterobacterales compared to aztreonam-avibactam.

Abstract

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.Antimicrobial susceptibility of Enterobacterales and resistant subsets of isolates from immunosuppressed patientsa Carbapenemase-producing CRE isolates.Abbreviations: CLSI, Clinical and Laboratory Standards Institute; US FDA, United States Food and Drug Administration; MDR, multidrug-resistant; CRE, carbapenem-resistant Enterobacterales; CBase, carbapenemase.Antimicrobial susceptibility of selected species collected from immunosuppressed patientsa % inhibited at ≤8 mg/L, the CLSI breakpoint for aztreonam. b Not tested or no breakpoint published by US FDA.Abbreviations: CLSI, Clinical and Laboratory Standards Institute; US FDA, United States Food and Drug Administration

Antimicrobial susceptibility of Enterobacterales and resistant subsets of isolates from immunosuppressed patients

a Carbapenemase-producing CRE isolates.

Abbreviations: CLSI, Clinical and Laboratory Standards Institute; US FDA, United States Food and Drug Administration; MDR, multidrug-resistant; CRE, carbapenem-resistant Enterobacterales; CBase, carbapenemase.

Antimicrobial susceptibility of selected species collected from immunosuppressed patients

a % inhibited at ≤8 mg/L, the CLSI breakpoint for aztreonam. b Not tested or no breakpoint published by US FDA.

Abbreviations: CLSI, Clinical and Laboratory Standards Institute; US FDA, United States Food and Drug Administration

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.

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.

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.

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

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