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

• Published in: Pharmacotherapy 2023-06, Vol.43 (6), p.502-513
• Main Authors: El‐Ghali, Amer, Kunz Coyne, Ashlan J., Caniff, Kaylee, Bleick, Callan, Rybak, Michael J.
• Format: Article
• Language: English
• Subjects: Acinetobacter baumannii; Acinetobacter Infections - drug therapy; Anti-Bacterial Agents - adverse effects; Antibiotics; Bacteremia; beta-Lactamase Inhibitors - pharmacology; beta-Lactamase Inhibitors - therapeutic use; Carbapenems - pharmacology; Carbapenems - therapeutic use; carbapenem‐resistant Acinetobacter baumannii (CRAB); Colistin; Colistin - pharmacology; Humans; Imipenem; Infections; Lactams - pharmacology; Lactams - therapeutic use; Morbidity; Pharmacodynamics; Pharmacokinetics; phase III ATTACK trial; Phlebitis; Pneumonia; Sulbactam; sulbactam‐durlobactam (SUL‐DUR); United States; β‐lactam‐β‐lactamase inhibitor
• ISSN: 0277-0008; 1875-9114
• DOI: 10.1002/phar.2802

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.