P-1362. Cefiderocol Activity against Carbapenem-resistant <i>Acinetobacter baumannii-calcoaceticus</i> complex, Including Molecularly Characterized Clinical Isolates, Causing Infections in United States Hospitals (2020–2023)

Abstract Background Multidrug-resistant (MDR) Acinetobacter baumannii-calcoaceticus complex (ACB) have gained attention as an important clinical challenge in the last decades, due to its ability to develop resistance to front-line antibiotics. Cefiderocol (FDC) is a siderophore cephalosporin that uses the iron transport systems of Gram-negative bacteria to optimize cell entry. The activity of FDC and comparators were evaluated against ACB causing infections in US hospitals, including resistant subsets, collected as part of the SENTRY Antimicrobial Surveillance Program. Methods 1,786 Acinetobacter spp. were collected from 36 sites in the US during 2020–2023. Susceptibility (S) testing was performed by broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparators and iron-depleted CAMHB for FDC. CLSI/EUCAST/FDA criteria were applied. Isolates with imipenem or meropenem MIC ≥4 mg/L (nonS by CLSI) were screened for β-lactamase genes. Results ACB comprised 80.5% (1,438/1,786) of isolates collected, and all 405 carbapenem-nonS isolates were identified as ACB. Carbapenemase genes were detected in 86.9% (352/405) of carbapenem-nonS ACB, and blaOXA-23 (59.9%; 211/352) prevailed, followed by blaOXA-24 (25.6%; 90/352), and blaOXA-72 (9.4%; 33/352). FDC (93.6–98.8%S) had MIC50 of 0.12 mg/L and MIC90 of 1 mg/L against all Acinetobacter spp. and the ACB subset (Table). Comparators had limited activity against these isolates (66.5–77.1%S), except for colistin (COL) (95.7–96.2%S). FDC (97.0–97.7%S by CLSI) had MIC50 of 0.25 mg/L and MIC90 of 2 mg/L against carbapenem-nonS ACB and those carrying carbapenemases. Only COL was also active against these 2 resistant subsets. FDC (97.2–100%S by CLSI) MIC90 of 2 mg/L, 1 mg/L and 0.5 mg/L were obtained against ACB carrying blaOXA-23, blaOXA-24, and blaOXA-72, respectively. Isolates carrying other carbapenemases were inhibited by FDC MIC of ≤2 mg/L, except for 1 strain with blaOXA-23 and blaNDM-1 (MIC, 8 mg/L). Conclusion This study demonstrates the MDR nature of ACB causing infections in US hospitals, and FDC as an active agent against these isolates, regardless of resistance genotype. These in vitro data suggest FDC as an important option for the treatment of infections caused by MDR ACB. Disclosures Rodrigo E. Mendes, PhD, GSK: Grant/Research Support