Angela De Haan (RIVM)

Summary of presentation:
Introduction: Acinetobacter baumannii complex (ABC) are opportunistic nosocomial pathogens with high propensity for multidrug-resistance. Novel β-lactam/β-lactamase inhibitor combinations such as sulbactam–durlobactam (SUD) or ampicillin-sulbactam (SAM) offer therapeutic promise against carbapenem-resistant A. baumannii (CRAb). The objectives of this study were: 1) to asses susceptibility to SUD and SAM for CRAb, and 2) identify determinants implicated in SUD and SAM resistance in CRAb in the Netherlands in 2024-2025.

Methods: A total of 94 isolates belonging to ABC from national surveillance in 2024-2025 were whole-genome sequenced (WGS, Illumina). The carbapenem inactivation method (CIM) was used to assess carbapenemase activity, and MIC for meropenem was determined using Etest. Susceptibility for SUD (10-µg/10-µg sulbactam/durlobactam, Hardy Diagnostics, USA) and SAM (10-µg/10-µg ampicillin/sulbactam, Oxoid, UK) were determined by disk diffusion. WGS was used to determine carbapenemase genes, mutations in penicillin-binding protein-3 (PBP3), multilocus sequence typing (MLST).

Results: Ninety-four CRAb isolates produced carbapenemase in the CIM and 90/94 were resistant for meropenem (EUCAST, R >8mg/L). Eleven of 94 (12%) isolates were resistant for SUD (CLSI M100 ED35:2025, S ≥17 mm, R ≤13 mm), 3/94 isolates were intermediate, and 83/94 isolates were susceptible. Eighty-eight of 94 (94%) isolates were resistant for SAM (CLSI S ≥22 mm, R ≤16 mm) correlating 27% with an Ala515Val mutation, 4% His370Tyr or 11% miscellaneous/multiple mutations in PBP3. The 11 SUD-resistant CRAb isolates were also resistant for SAM, were of >8 distinct MLST STs carried mostly (9/11) New Delhi metallo-β-lactamases type (NDM-type).

Conclusion: CRAb showed extensive resistance of 12% and 94% for SUD and SAM in the Netherlands in 2024–2025, respectively. SUD-SAM resistance correlated with NDM-type carbapenemases, and SAM resistance correlated in 42% of CRAb with alterations in PBP3. Continued national surveillance combined with antimicrobial stewardship and cautious clinical deployment of SUD and SAM are recommended to monitor resistance to these last-resort antibiotics.