Sulbactam-durlobactam: A novel β-lactam-β-lactamase inhibitor combination targeting carbapenem-resistant Acinetobacter baumannii infections

Pharmacotherapy. 2023 Jun;43(6):502-513. doi: 10.1002/phar.2802. Epub 2023 May 23.

Abstract

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a difficult-to-treat nosocomial pathogen responsible for significant morbidity and mortality. Sulbactam-durlobactam (SUL-DUR), formerly ETX2514SUL, is a novel β-lactam-β-lactamase inhibitor designed specifically for the treatment of CRAB infections. The United States Food and Drug Administration (FDA) fast-track approval of SUL-DUR for the treatment of CRAB infections is currently pending after completion of the phase III ATTACK trial, which compared SUL-DUR to colistin, both in combination with imipenem-cilastatin (IMI) for patients with CRAB-associated hospital-acquired bacterial pneumonia, ventilator-associated pneumonia, and bacteremia. The results of this trial demonstrated that SUL-DUR was non-inferior to colistin for CRAB while also possessing a much more favorable safety profile. SUL-DUR was well-tolerated with the most common side effects being headache, nausea, and injection-site phlebitis. With the current landscape of limited effective treatment options for CRAB infections, SUL-DUR represents a promising therapeutic option for the treatment of these severe infections. This review will discuss the pharmacology, spectrum of activity, pharmacokinetics/pharmacodynamics, in vitro and clinical studies, safety, dosing, administration, as well as the potential role in therapy for SUL-DUR.

Keywords: Acinetobacter baumannii; carbapenem-resistant Acinetobacter baumannii (CRAB); phase III ATTACK trial; sulbactam-durlobactam (SUL-DUR); β-lactam-β-lactamase inhibitor.

Publication types

  • Review

MeSH terms

  • Acinetobacter Infections* / drug therapy
  • Acinetobacter baumannii*
  • Anti-Bacterial Agents / adverse effects
  • Carbapenems / pharmacology
  • Carbapenems / therapeutic use
  • Colistin / pharmacology
  • Humans
  • Lactams / pharmacology
  • Lactams / therapeutic use
  • United States
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamase Inhibitors / therapeutic use

Substances

  • sulbactam-durlobactam
  • beta-Lactamase Inhibitors
  • Anti-Bacterial Agents
  • Colistin
  • Lactams
  • Carbapenems