Characterization of Acinetobacter baumannii-calcoaceticus complex isolates and microbiological outcome for patients treated with sulbactam-durlobactam in a phase 3 trial (ATTACK)

Antimicrob Agents Chemother. 2024 May 2;68(5):e0169823. doi: 10.1128/aac.01698-23. Epub 2024 Apr 3.

Abstract

Acinetobacter baumannii-calcoaceticus complex (ABC) causes severe, difficult-to-treat infections that are frequently antibiotic resistant. Sulbactam-durlobactam (SUL-DUR) is a targeted β-lactam/β-lactamase inhibitor combination antibiotic designed to treat ABC infections, including those caused by multidrug-resistant strains. In a global, pathogen-specific, randomized, controlled phase 3 trial (ATTACK), the efficacy and safety of SUL-DUR were compared to colistin, both dosed with imipenem-cilastatin as background therapy, in patients with serious infections caused by carbapenem-resistant ABC. Results from ATTACK showed that SUL-DUR met the criteria for non-inferiority to colistin for the primary efficacy endpoint of 28-day all-cause mortality with improved clinical and microbiological outcomes compared to colistin. This report describes the characterization of the baseline ABC isolates from patients enrolled in ATTACK, including an analysis of the correlation of microbiological outcomes with SUL-DUR MIC values and the molecular drivers of SUL-DUR resistance.

Keywords: Acinetobacter baumannii; sulbactam-durlobactam; β-lactamase inhibitor.

Publication types

  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't
  • Randomized Controlled Trial

MeSH terms

  • Acinetobacter Infections* / drug therapy
  • Acinetobacter Infections* / microbiology
  • Acinetobacter baumannii* / drug effects
  • Acinetobacter calcoaceticus / drug effects
  • Acinetobacter calcoaceticus / genetics
  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Azabicyclo Compounds / pharmacology
  • Azabicyclo Compounds / therapeutic use
  • Cilastatin, Imipenem Drug Combination / therapeutic use
  • Colistin* / pharmacology
  • Colistin* / therapeutic use
  • Drug Resistance, Multiple, Bacterial
  • Humans
  • Male
  • Microbial Sensitivity Tests*
  • Sulbactam* / pharmacology
  • Sulbactam* / therapeutic use

Substances

  • Sulbactam
  • Anti-Bacterial Agents
  • Colistin
  • Azabicyclo Compounds
  • durlobactam
  • Cilastatin, Imipenem Drug Combination