Activity of ampicillin-sulbactam, sulbactam-durlobactam, and comparators against Acinetobacter baumannii-calcoaceticus complex strains isolated from respiratory and bloodstream sources: results from ACNBio study - PubMed (original) (raw)

. 2025 Aug 6;69(8):e0037925.

doi: 10.1128/aac.00379-25. Epub 2025 Jul 17.

Jill Argotsinger 2, Eric T Beck 3, Robin R Chamberland 4, Andrew E Clark 5, Anne R Daniels 6, Rachael Liesman 6 7 8, Mark Fisher 9 10, Philip Gialanella 11, Jonathan Hand 12, Amanda T Harrington 13, Romney M Humphries 14, Holly Huse 15, Robert Hamilton-Seth 15, Julia D Hankins 16, Wesley D Kufel 17 18 19, Scott W Riddell 17 19, Jamie Marino 20, Lars F Westblade 20 21, A Brian Mochon 22 23 24, Navaneeth Narayanan 25, Thomas J Kirn 26, Virginia M Pierce 27, Raghava Potula 28, Tsigereda Tekle 29, Patricia J Simner 29, Robert J Tibbetts 30, Christine Vu 31, Lilian M Abbo 31 32, Octavio Martinez 31 32, Rebekah E Dumm 33, David P Nicolau 1 34, Tomefa E Asempa 1; Acinetobacter baumannii Complex National Biorepository (ACNBio) Study Group

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Activity of ampicillin-sulbactam, sulbactam-durlobactam, and comparators against Acinetobacter baumannii-calcoaceticus complex strains isolated from respiratory and bloodstream sources: results from ACNBio study

Ecem Buyukyanbolu et al. Antimicrob Agents Chemother. 2025.

Abstract

Infections caused by carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex (ABC) are associated with high mortality rates and limited treatment options. This study aims to evaluate the in vitro activity of clinically utilized antimicrobials against a contemporary collection of ABC isolates with a predominant carbapenem-resistant phenotype. Geographically dispersed US medical centers (n = 22) provided non-duplicate respiratory and bloodstream ABC isolates for surveillance testing. Antimicrobial susceptibility testing was conducted by broth microdilution and interpreted according to Clinical & Laboratory Standards Institute (CLSI) and Food and Drug Administration (FDA) breakpoints. ABC isolates (n = 523) from respiratory tract (74.4%) and blood (25.6%) sources were recovered from patients (2023-2024). Forty percent were obtained from intensive care unit patients. Carbapenem non-susceptibility was observed in 76.9% of isolates and was more common among respiratory tract cultures. The addition of durlobactam to sulbactam decreased the MIC90 by three-doubling dilutions from 32 to 4 µg/mL, increasing the susceptibility rate to 96.9% from 33.8%. Genome sequencing of sulbactam-durlobactam non-susceptible isolates (16/523; n = 3.1%) revealed MBL and non-enzymatic resistance mechanisms. Cefiderocol inhibited 93.5% and 76.1% of isolates at CLSI and FDA susceptible breakpoints, respectively. Minocycline susceptibility was <50%, while tigecycline and eravacycline MIC50/90 were 1/2 and 0.5/1 µg/mL, respectively. Sulbactam-durlobactam displayed high activity against sulbactam (95.4%), carbapenem (96.3%), and cefiderocol (95.2%) non-susceptible isolates. Susceptibility rates of clinically utilized antimicrobials against a US collection of ABC isolates ranged from 23% to 97%, with meropenem displaying the lowest rate and sulbactam-durlobactam demonstrating the highest overall rate. Sulbactam-durlobactam activity was preserved against sulbactam, carbapenem, and cefiderocol non-susceptible isolates among respiratory tract and bloodstream isolates.

Keywords: Acinetobacter; CRAB; sulbactam; sulbactam-durlobactam.

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Conflict of interest statement

A.B.M. has received research funding from Shionogi. A.T.H. has received research funding from Beckman Coulter, bioMeriuexbioMérieux, Bio-Rad, and Selux. R.L. has served as a consultant for Gradientech. W.D.K. received research grants from Merck & Co., and Melinta Therapeutics and received consultation fees from Shionogi. D.P.N. served as a consultant, speaker's bureau member, or has received research funding from Abbvie, Cepheid, Innoviva, Pfizer, Wockhardt, Shionogi, Venatorx. T.E.A. has received research funding from Venatorx, Paratek, Shionogi, Innoviva, and Spero Therapeutics. All other authors report no relevant disclosures.

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