Efficacy of ceftazidime/avibactam against 10 clinical isolates of Pseudomonas aeruginosa in icodextrin-based peritoneal dialysis solution and patient-derived dialysate

BACKGROUND: Peritoneal dialysis (PD) enables intraperitoneal antibiotic delivery, but the efficacy of ceftazidime/avibactam (CAZ/AVI) in PD fluid (PDF) is not well-characterized. OBJECTIVES: To assess the in vitro activity of ceftazidime/avibactam against Pseudomonas aeruginosa in fresh PDF and patient-derived dialysate at isolate-specific MIC levels and at a clinically measured intraperitoneal peak concentration (Cmax). METHODS: MICs were determined for P. aeruginosa ATCC 27583 and nine clinical isolates using broth microdilution in CAMHB. Two isolates (123/19, 174/19) underwent time-kill experiments at MIC (8-16 µg/mL) and maximum peritoneal concentration (Cmax 64 µg/mL), with avibactam fixed at 4 µg/mL. Bacterial counts were evaluated over 24 h in CAMHB, icodextrin-containing PDF, and patient-derived dialysate (n = 4). RESULTS: Isolates showed variable growth. Ceftazidime/avibactam was bactericidal in CAMHB but only bacteriostatic in PDF and patient-derived dialysate (±1 log10 cfu/mL reduction at 8 h). No further reduction occurred at 24 h, even at Cmax. CONCLUSIONS: Reduced bacterial growth in PDF is associated with diminished ceftazidime/avibactam activity, yielding primarily bacteriostatic effects. Single-dose intraperitoneal administration may be insufficient to eradicate P. aeruginosa, as Cmax concentrations failed to achieve ≥3 log10 cfu/mL reduction in vitro. These findings highlight potential limitations of ceftazidime/avibactam in PD-related infections and might guide future dosing strategies research.