Antimicrobial activity of sulbactam-durlobactam against <i>Acinetobacter baumannii-calcoaceticus</i> complex strains causing non-respiratory and non-bloodstream infections from the United States (2023–2025)

<i>Acinetobacter baumannii</i> most often causes pneumonia in critically ill patients. However, <i>A. baumannii</i> is also an important cause of a broader range of infections, including skin/wound and urinary tract infections. This study aims to evaluate the <i>in vitro</i> activity of sulbactam-durlobactam and comparator antibiotics, including meropenem and cefiderocol against <i>A. baumannii-calcoaceticus</i> complex isolates from non-respiratory and non-bloodstream sources. Samples included 285 <i>A. baumannii-calcoaceticus</i> complex isolates enriched for carbapenem resistance collected across 17 states in the United States (January 2023-May 2025). Antimicrobial susceptibility tests were conducted by manual broth microdilution and interpreted according to Clinical and Laboratory Standards Institute (CLSI) and Food and Drug Administration (FDA) (cefiderocol) standards. <i>A. baumannii</i> complex isolates were primarily cultured from skin/wound (58.6%), urinary tract (31.6%), and other sources (9.8%), including cerebrospinal and peritoneal fluid. Carbapenem resistance was observed in approximately 70% of isolates and more common among skin/wound cultures. Sulbactam-durlobactam was observed to be highly active (96.9% susceptible [S]; MIC₉₀ 4 mg/L) and demonstrated greater activity than sulbactam (37.9% S; MIC₉₀ 32 mg/L). Sulbactam-durlobactam also displayed high susceptibility rates across isolate sources, ranging from 96.4 (skin/wound) to 97.8% (urine). Cefiderocol demonstrated similar <i>in vitro</i> activity across culture sources and patient location, inhibiting >90 and >80% of isolates at CLSI and FDA susceptible breakpoints, respectively. Minocycline susceptibility was 69.1%, while tigecycline and eravacycline MICs_50/90 were 1/4 and 0.5/1 mg/L, respectively. The observed data are consistent with results from surveillance studies among respiratory and bloodstream isolates and show that sulbactam-durlobactam demonstrates potent <i>in vitro</i> activity against clinical <i>A. baumannii</i> complex isolates from a variety of culture sources.IMPORTANCE<i>Acinetobacter baumannii</i> is a difficult-to-treat pathogen that often affects hospitalized patients and is known for a high level of multi-drug resistance. While commonly associated with pneumonia, it also causes infections in wounds, the urinary tract, and other parts of the body. This study shows that sulbactam-durlobactam is highly effective against <i>A. baumannii</i> from various infection sites. The results are important because they can inform clinicians on the susceptibility profiles of <i>A. baumannii</i> from a variety of infection sources, not just lung and bloodstream. As new antibiotics come onto the market, it is important to continuously assess resistance patterns to inform patient and system-wide health decisions.