P-1215. In vitro activity of Sulbactam-durlobactam and Standard-of-Care Antibiotics against Acinetobacter baumannii-calcoaceticus complex isolates from wound and urinary tract sources: ACNBio Study 2023-2025

TL;DR

This study shows that sulbactam-durlobactam is highly effective against Acinetobacter baumannii isolates from wounds and urinary tract infections, even those resistant to other antibiotics.

Contribution

The study provides new in vitro evidence of sulbactam-durlobactam's efficacy against A. baumannii from non-respiratory and non-bloodstream sources.

Findings

Sulbactam-durlobactam showed 98.5% susceptibility against A. baumannii isolates, outperforming ampicillin-sulbactam and meropenem.

It retained high activity (97.7% susceptible) against carbapenem-resistant isolates.

The drug demonstrated consistent effectiveness across different infection sources like skin and urine.

Abstract

Acinetobacter baumannii most often causes nosocomial bacteremia and pneumonia. However, A. baumannii is becoming an important cause of a broader range of infections including skin and soft tissue infection (SSTI) and urinary tract infections (UTI). This study aims to evaluate the in vitro activity of sulbactam-durlobactam and other clinically utilized antibiotics against A. baumannii-calcoaceticus complex isolates isolated from non-respiratory and non-bloodstream sources.

Samples included 193 A. baumannii-calcoaceticus complex isolates collected from 2023-2025 across 19 states. 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 and FDA (cefiderocol) standards.

A. baumannii complex isolates were primarily cultured from skin and soft tissue (56.5%), followed by urinary tract (31.6%) and other sources (11.9%) including bone biopsy, fluid aspirate etc. ICU patients contributed 20% of the isolates. Sulbactam-durlobactam was observed to be highly active (98.5% susceptible [S]; MIC50/90 1/4 mg/L), demonstrating greater activity than ampicillin-sulbactam (41.5% S; MIC50/90 8/32 mg/L) and meropenem (32.1% S; MIC50/90 32/128 mg/L). Sulbactam-durlobactam also displayed high susceptibility rates across sample sources, ranging from 97.3% (skin and soft tissue) to 100% (urine). The MIC50/90 and susceptibility rates for all other agents including tetracycline derivatives are shown in Table 1. Notably, among the carbapenem-resistant A. baumannii (CRAB) isolates (n=130) in the collection, sulbactam-durlobactam retained high activity (97.7% S) relative to ampicillin-sulbactam (16.2% S). Cefiderocol inhibited 97.7% and 75.4% of isolates at CLSI and FDA susceptible breakpoints, respectively.

The data reported here are consistent with results from surveillance studies among non-respiratory and bloodstream isolates and show that sulbactam-durlobactam demonstrates in vitro activity against clinical A. baumannii complex isolates from urinary tract and SSTI sources, including isolates that are resistant to ampicillin-sulbactam, carbapenems, and cefiderocol.

Tomefa E. Asempa, PharmD, Innoviva: Grant/Research Support Robin R. Chamberland, PhD D(ABMM), bioMerieux: Advisor/Consultant|Pattern Bioscience, Inc.: Advisor/Consultant|Pattern Bioscience, Inc.: Grant/Research Support Jonathan Hand, MD, AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Ferring: Grant/Research Support|Innoviva: Advisor/Consultant|Janssen: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Scynexis: Grant/Research Support|The Antibiotic Resistance Leadership Group (ARLG): Grant/Research Support|The Antibiotic Resistance Leadership Group (ARLG): Honoraria Amanda Harrington, PhD, Beckman Coulter: Grant/Research Support|bioMerieux/BioFire: Advisor/Consultant|bioMerieux/BioFire: Grant/Research Support|bioMerieux/BioFire: Honoraria|BioRad: Advisor/Consultant|Selux: Grant/Research Support Wesley D. Kufel, Pharm.D., BCPS, BCIDP, Merck & Co.: Grant/Research Support|Shionogi, Inc: Grant/Research Support|Shionogi, Inc: Honoraria Lars Westblade, PhD, Elements Materials Technology: Grant/Research Support|Hardy Diagnostics: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Selux Diagnostics: Grant/Research Support|Shionogi: Advisor/Consultant|SNIPRBIOME: Grant/Research Support Thomas Kirn, MD PhD, BD: Advisor/Consultant|BD: Honoraria Brian Mochon, PhD, D(ABMM), Shionogi: Advisor/Consultant Mark Fisher, PhD, Shionogi Inc.: Advisor/Consultant Rebekah Dumm, PhD D(ABMM), BD: Advisor/Consultant|BD: Grant/Research Support|Biomerieux: Advisor/Consultant|Biomerieux: Grant/Research Support|Diasorin: Grant/Research Support|Pattern Biosciences: Grant/Research Support|Qiagen: Grant/Research Support|Roche Diagnostics: Advisor/Consultant|Shionogi: Advisor/Consultant David P. Nicolau, PharmD, CARB-X: Grant/Research Support|Innoviva: Advisor/Consultant|Innoviva: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support

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