Understanding Acinetobacter baumannii Resistance to Sulbactam-Durlobactam: A Clinical Perspective

Current in vitro data show a generally favorable susceptibility of Acinetobacter baumannii complex to sulbactam-durlobactam, shifting therapeutic options for difficult-to-treat Gram-negative infections.

Resistance proportions to sulbactam-durlobactam are low (1.2%–4.6% across 10,412 isolates) and non-susceptibility remains uncommon in non-baumannii complex species. This pooled in vitro dataset demonstrates activity against most clinical isolates and reports carbapenem-resistant subsets with resistance ranging 0%–5.2%, which has direct implications for empiric coverage in high-risk patients. Non-consecutive, highly selected cohorts show higher resistance (up to 27.3% in selected cefiderocol-reduced-susceptibility isolates), so clinicians should interpret aggregate rates alongside local strain selection pressures, as summarized in the sulbactam‑durlobactam review.

OXA-type beta-lactamases, particularly OXA-23 variants, are frequently detected and commonly coexist with other resistance determinants in A. baumannii isolates. Mechanistically, OXA enzymes hydrolyze beta-lactams and reduce sulbactam susceptibility, while durlobactam inhibits many serine Class D β-lactamases to restore sulbactam activity but does not inhibit metallo-β-lactamases (e.g., NDM) or overcome resistance driven by certain PBP insertions or other non-β-lactamase mechanisms. These molecular patterns and their clinical implications are detailed in the systematic review, which supports targeted molecular and phenotypic testing when resistance is suspected.