Sulbactam-Durlobactam in the Treatment of Multidrug-Resistant Acinetobacter baumannii: A Narrative Review

The increasing prevalence of infections caused by multidrug-resistant (MDR) Gram-negative bacteria represents a major global public health challenge. Among hospital-acquired infections (HAIs), ventilator-associated pneumonia (VAP) caused by non-fermenting Gram-negative pathogens, particularly the Acinetobacter baumannii-calcoaceticus complex, it is associated with limited therapeutic options and high mortality. Sulbactam-durlobactam is a novel combination consisting of sulbactam, a β-lactamase inhibitor with intrinsic activity against Acinetobacter spp., and durlobactam, a diazabicyclooctane β-lactamase inhibitor targeting Ambler class A, C, and D enzymes. This review summarizes current evidence on the pharmacological properties, clinical efficacy, and resistance mechanisms associated with this combination. Clinical trials have demonstrated that sulbactam-durlobactam is non-inferior to colistin in the treatment of infections caused by carbapenem-resistant A. baumannii, with a significantly lower risk of nephrotoxicity. The combination is generally well tolerated and represents a promising therapeutic option for difficult-to-treat infections. However, emerging resistance mechanisms, including PBP3 mutations, metallo-β-lactamase production, and efflux pump overexpression, may limit its long-term effectiveness. Further research is required to better understand resistance development and optimize clinical use.