A Comprehensive Monograph on Sulbactam: From β-Lactamase Inhibition to a Renewed Strategy Against Multidrug-Resistant Pathogens

Executive Summary

Sulbactam is a semi-synthetic, small-molecule drug belonging to the penicillanic acid sulfone class, identified by DrugBank ID DB09324 and CAS Number 68373-14-8. Initially developed as a β-lactamase inhibitor, its primary function is to irreversibly bind to and inactivate a wide range of bacterial β-lactamase enzymes, thereby protecting co-administered β-lactam antibiotics from degradation. This mechanism restores and expands the antibacterial spectrum of partners such as ampicillin and cefoperazone, making these combinations effective against numerous common pathogens.

Beyond this protective role, Sulbactam possesses a unique and clinically significant intrinsic antibacterial activity, particularly against Acinetobacter baumannii, a pathogen of critical global concern. This direct bactericidal effect is mediated through the inhibition of essential penicillin-binding proteins (PBPs), a characteristic that distinguishes it from many other β-lactamase inhibitors. This dual mechanism of action—acting as both a shield and a direct-acting agent—has facilitated Sulbactam's enduring relevance and recent resurgence in clinical practice.

Pharmacokinetically, Sulbactam is administered parenterally and exhibits a profile that is well-matched to its common partner, ampicillin, with a short half-life of approximately one hour and primary elimination via the kidneys. This synergy simplifies dosing, including necessary adjustments in patients with renal impairment.