In Vitro Activity of Cefiderocol, Ceftazidime-Avibactam, Imipenem-Relebactam and Ceftolozane-Tazobactam Against Carbapenem-Resistant Pseudomonas aeruginosa: A Multicenter Surveillance Study Across 8 Chinese Provinces

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global health threat. New β-lactam/β-lactamase inhibitor (BL/BLI) combinations and cefiderocol offer treatment options, but head-to-head comparisons against Chinese clinical isolates are lacking. Methods: We collected 442 non-duplicate clinical P. aeruginosa isolates from respiratory specimens at 10 hospitals across 8 Chinese provinces (2017–2025); the collection was CRPA-enriched. Minimum inhibitory concentrations (MICs) were determined by reference broth microdilution, with cefiderocol (FDC) tested in iron-depleted cation-adjusted Mueller–Hinton broth. Susceptibility was interpreted using CLSI 2025 breakpoints for FDC, ceftazidime-avibactam (CZA), imipenem-relebactam (IMR), and ceftolozane-tazobactam (CT). Results: FDC showed the highest susceptibility at 97.3% (MIC50/90, 0.25/2 mg/L). Eleven isolates (2.5%) were FDC-intermediate and only one (0.2%) was FDC-resistant. CZA susceptibility was 71.3% (MIC50/90, 4/32 mg/L); CT, 65.8% (4/64 mg/L); IMR, 49.5% (4/16 mg/L). IMR had the highest intermediate rate (26.7%). No isolate was resistant to all four agents; pan-susceptibility was 38.9%. MICs were strongly correlated among CZA, IMR, and CT (Pearson r = 0.545–0.773) and weakly correlated between FDC and the BL/BLIs (r = 0.259–0.521), consistent with shared resistance mechanisms among the former. FDC susceptibility remained above 95% throughout the study period. In descriptive analyses, CZA and CT susceptibility each declined by approximately 15 percentage points from 2017–2018 to 2024–2025. Conclusions: In this CRPA-enriched Chinese collection, FDC was the most active and stable agent. CZA, IMR, and CT showed lower susceptibility, substantial cross-resistance, and declining trends. These findings indicate that FDC retained the highest and most stable in vitro activity against CRPA among the agents studied, supporting its evaluation as a treatment option for CRPA where available; the choice of therapy should nevertheless also take the site and severity of infection, prior antibiotic exposure, and local epidemiology into account. CZA, IMR, and CT should be used only after susceptibility confirmation.