511. Activity of Sulbactam-durlobactam and Standard-of-Care Antibiotics against Acinetobacter baumannii-calcoaceticus complex isolates acquired from Hospitalized Patients in the United States (2023 – 2024)
Authors: Buyukyanbolu Ecem , Argotsinger Jill , Beck Eric T , Chamberland Robin R , Clark Andrew E , Gialanella Philip , Loeb Matthew , Sears Amy , Harrington Amanda , Humphries Romney , Kufel Wesley D , Riddell Scott W , Mochon A Brian , Vu Christine A , Abbo Lilian M , Martinez Octavio , Marino Jamie , Westblade Lars , Nicolau David P , Asempa Tomefa E 
Published: January 2025

Abstract

Background
Acinetobacter baumannii-calcoaceticus complex (ABC) isolates are responsible for severe infections, such as bacteremia, healthcare-associated pneumonia, and skin and soft tissue infections. Sulbactam-durlobactam is a FDA-approved targeted β-lactam-β-lactamase inhibitor combination antibiotic developed to treat infections caused by ABC. This study aims to evaluate the in vitro activity of sulbactam-durlobactam and clinically utilized antibiotics against ABC strains with a predominance of carbapenem resistance.Table 1.Susceptibility test results of sulbactam-durlobactam and comparator agents against Acinetobacter baumannii-calcoaceticus complex isolates

Methods
164 ABC isolates in addition to de-identified data including patient location at the time of culture and culture source were submitted by 11 geographically dispersed U.S medical centers in 2023 and 2024. Susceptibility tests for sulbactam-durlobactam (durlobactam fixed concentration of 4 mg/L), and comparator agents were conducted by manual broth microdilution and interpreted according to CLSI M100Ed34 standards. Carbapenem-resistant ABC (CRAB) was defined by phenotypic resistance to meropenem (MIC ≥8 mg/L).

Results
ABC isolates were primarily cultured from respiratory sources (57%), followed by blood (19%) and urine (11%). Of the 164 isolates, majority were isolated from non-ICU patients (n=102; 62%) versus ICU (n=62; 38%). The MIC50 and MIC90 values of the sulbactam component of ampicillin-sulbactam for all isolates was 8 and 32 mg/L, respectively resulting in a susceptibility rate of 40.8%. The addition of durlobactam to sulbactam decreased the MIC50 and MIC90 by 2-doubling dilutions to 1 and 4 mg/L and increased the susceptibility rate to 94.5%. The MIC50/90 and susceptibility rates for all other antimicrobial agents are shown in Table 1. Notably, a majority of isolates were CRAB (n=122; 74.4%) and among these isolates, sulbactam-durlobactam MIC50, MIC90, and %S was 2, 4 mg/L, and 92.6%, respectively.

Conclusion
Sulbactam-durlobactam demonstrated potent in vitro activity against a contemporary challenge set of clinical ABC isolates, including carbapenem-resistant isolates among hospitalized patients in the United States. This study highlights the important role of sulbactam-durlobactam, relative to other clinically utilized agents for the treatment of infections caused by ABC isolates.

Disclosures
Amanda Harrington, PhD, Beckman Coulter: Advisor/Consultant|bioMeriuex: Advisor/Consultant|bioMeriuex: Grant/Research Support|Bio-Rad: Advisor/Consultant|Day Zero: Advisor/Consultant|Selux Diagnostics: Grant/Research Support Wesley D. Kufel, Pharm.D., BCPS, BCIDP, Merck & Co.: Grant/Research Support|Shionogi, Inc: Grant/Research Support Lars Westblade, PhD, Accelerate Diagnostics, Inc: Grant/Research Support|bioMerieux, Inc: Grant/Research Support|Element Materials Technology: Grant/Research Support|Hardy Diagnostics: Grant/Research Support|Roche Molecular Systems, Inc.: Advisor/Consultant|Roche Molecular Systems, Inc.: Grant/Research Support|Selux Diagnostics, Inc.: Grant/Research Support|Shionogi, Inc: Advisor/Consultant|Talis Biomedical: Advisor/Consultant David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Grant/Research Support|Innoviva: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Venatorx: Grant/Research Support Tomefa E. Asempa, PharmD, FDA/CDER: Grant/Research Support|Paratek: Grant/Research Support|Shionogi: Grant/Research Support|Spero: Grant/Research Support|VenatoRx: Grant/Research Support