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 Buyukyanbolu¹, Jill Argotsinger², Eric T Beck³, Robin R Chamberland⁴, Andrew E Clark⁵, Anne R Daniels⁶, Rachael Liesman^{6

7

8}, Mark Fisher^{9

10}, Philip Gialanella¹¹, Jonathan Hand¹², Amanda T Harrington¹³, Romney M Humphries¹⁴, Holly Huse¹⁵, Robert Hamilton-Seth¹⁵, Julia D Hankins¹⁶, Wesley D Kufel^{17

18

19}, Scott W Riddell^{17

19}, Jamie Marino²⁰, Lars F Westblade^{20

21}, A Brian Mochon^{22

23

24}, Navaneeth Narayanan²⁵, Thomas J Kirn²⁶, Virginia M Pierce²⁷, Raghava Potula²⁸, Tsigereda Tekle²⁹, Patricia J Simner²⁹, Robert J Tibbetts³⁰, Christine Vu³¹, Lilian M Abbo^{31

32}, Octavio Martinez^{31

32}, Rebekah E Dumm³³, David P Nicolau^{1

34}, Tomefa E Asempa¹; Acinetobacter baumannii Complex National Biorepository (ACNBio) Study Group

Affiliations

¹ Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
² Advocate Lutheran General Hospital, Park Ridge, Illinois, USA.
³ Department of Microbiology, ACL Laboratories, Milwaukee, Wisconsin, USA.
⁴ Department of Pathology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
⁵ Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
⁶ Froedtert & Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁷ Department of Pathology, Froedtert & Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁸ Wisconsin Diagnostic Labs, Milwaukee, Wisconsin, USA.
⁹ Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
¹⁰ Associated Regional and University Pathologists (ARUP) Laboratories, Salt Lake City, Utah, USA.
¹¹ Department of Pathology, Albert Einstein College of Medicine, Montefiore Medical Center, New York, New York, USA.
¹² Department of Infectious Diseases, Ochsner Health, New Orleans, Louisiana, USA.
¹³ Loyola University Medical Center, Maywood, Illinois, USA.
¹⁴ Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹⁵ Department of Pathology, Harbor-UCLA Medical Center, Torrance, California, USA.
¹⁶ Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
¹⁷ State University of New York Upstate University Hospital, Syracuse, New York, USA.
¹⁸ Binghamton University School of Pharmacy and Pharmaceutical Sciences, Binghamton, New York, USA.
¹⁹ State University of New York Upstate Medical University, Syracuse, New York, USA.
²⁰ Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA.
²¹ Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
²² Banner Health, Phoenix, Arizona, USA.
²³ Sonora Quest Laboratories, Phoenix, Arizona, USA.
²⁴ Department of Pathology, University of Arizona College of Medicine, Phoenix, Arizona, USA.
²⁵ Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.
²⁶ Department of Pathology & Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
²⁷ Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
²⁸ Pathology and Laboratory Medicine, Temple University Health System, Philadelphia, Pennsylvania, USA.
²⁹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³⁰ Pathology and Laboratory Medicine, Henry Ford Health, Detroit, Michigan, USA.
³¹ Department of Pharmacy, Jackson Health System, Miami, Florida, USA.
³² Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
³³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
³⁴ Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA.

PMID: 40673757
PMCID: PMC12326961
DOI: 10.1128/aac.00379-25

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.

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

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

Authors

Affiliations

¹ Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
² Advocate Lutheran General Hospital, Park Ridge, Illinois, USA.
³ Department of Microbiology, ACL Laboratories, Milwaukee, Wisconsin, USA.
⁴ Department of Pathology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
⁵ Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
⁶ Froedtert & Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁷ Department of Pathology, Froedtert & Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
⁸ Wisconsin Diagnostic Labs, Milwaukee, Wisconsin, USA.
⁹ Department of Pathology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
¹⁰ Associated Regional and University Pathologists (ARUP) Laboratories, Salt Lake City, Utah, USA.
¹¹ Department of Pathology, Albert Einstein College of Medicine, Montefiore Medical Center, New York, New York, USA.
¹² Department of Infectious Diseases, Ochsner Health, New Orleans, Louisiana, USA.
¹³ Loyola University Medical Center, Maywood, Illinois, USA.
¹⁴ Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹⁵ Department of Pathology, Harbor-UCLA Medical Center, Torrance, California, USA.
¹⁶ Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
¹⁷ State University of New York Upstate University Hospital, Syracuse, New York, USA.
¹⁸ Binghamton University School of Pharmacy and Pharmaceutical Sciences, Binghamton, New York, USA.
¹⁹ State University of New York Upstate Medical University, Syracuse, New York, USA.
²⁰ Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA.
²¹ Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, New York, USA.
²² Banner Health, Phoenix, Arizona, USA.
²³ Sonora Quest Laboratories, Phoenix, Arizona, USA.
²⁴ Department of Pathology, University of Arizona College of Medicine, Phoenix, Arizona, USA.
²⁵ Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, USA.
²⁶ Department of Pathology & Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
²⁷ Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
²⁸ Pathology and Laboratory Medicine, Temple University Health System, Philadelphia, Pennsylvania, USA.
²⁹ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
³⁰ Pathology and Laboratory Medicine, Henry Ford Health, Detroit, Michigan, USA.
³¹ Department of Pharmacy, Jackson Health System, Miami, Florida, USA.
³² Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
³³ Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
³⁴ Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA.

PMID: 40673757
PMCID: PMC12326961
DOI: 10.1128/aac.00379-25

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 MIC_50/90 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.

References

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

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MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous