Pharmacokinetic drug evaluation of co-packaged sulbactam for injection and durlobactam for injection for the treatment of Acinetobacter baumannii-calcoaceticus complex in HABP/VABP.

INTRODUCTION: Carbapenem-resistant Acinetobacter baumannii (CRAB) is an urgent-priority pathogen that is associated with high mortality and leaves clinicians reliant on nephrotoxic salvage regimens. Sulbactam/durlobactam (S/D) pairs sulbactam's intrinsic anti-Acinetobacter activity with the broad Ambler class A/C/D β-lactamase inhibitor durlobactam, creating the first agent targeting CRAB.

AREAS COVERED: Literature and abstracts from 2013 to 2025 were retrieved through PubMed, Embase, and major infectious diseases conferences. This review synthesizes S/D's chemistry, mechanism of action, resistance pathways, in vitro activity, pharmacokinetics, and pharmacodynamics. Clinical data introduces its early efficacy and highlights a phase 3 pivotal clinical trial (ATTACK) in hospital-acquired bacterial and ventilator-associated bacterial pneumonia (HABP/VABP), and briefly summarizes case reports of compassionate use in meningitis. Safety findings in these studies are summarized as well.

EXPERT OPINION: S/D has the potential to replace polymyxin-based therapy for directed CRAB therapy due to its targeted spectrum of activity and renal safety. Notably, S/D is inappropriate for isolates harboring class B metallo-β-lactamases and/or certain penicillin-binding proteins-3 (PBP3) mutations, those with S/D minimum inhibitory concentration (MIC) ≥4 mcg/mL and in populations with data gaps. Pharmacovigilance, studies of use in broader populations, and cost-effectiveness will be critical to maximize its clinical and stewardship value.