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

  • Antimicrob Agents Chemother. 2025 Aug 6;69(8):e0037925. doi: 10.1128/aac.00379-25.
Ecem Buyukyanbolu  1 ,  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
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 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 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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