Therapeutic drug monitoring of aztreonam-avibactam in critically ill patients with CRKP infections and variable renal function: A case series.

OBJECTIVES

Aztreonam-avibactam (ATM-AVI) is a novel β-lactam/β-lactamase inhibitor combination for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP), but pharmacokinetic data on ATM-AVI in patients undergoing continuous renal replacement therapy (CRRT) or recovering from acute kidney injury (AKI) remain scarce.

METHODS

We report on three critically ill CRKP-infected patients with distinct renal trajectories in this case series: (1) progressive AKI requiring continuous venovenous hemodiafiltration (CVVHDF), comparing Oxiris vs. HF12 filters; (2) AKI with slow renal recovery; (3) AKI with rapid renal recovery. Steady-state trough concentrations were measured. Pharmacokinetic/pharmacodynamic targets were 100% fT > 4-8×MIC for ATM and 100% fT > 4 mg/L for AVI. In case 1, CVVHDF clearance (ClCVVHDF) was additionally quantified.

RESULTS

All patients achieved clinical and microbiological cure with 100% target attainment. CVVHDF significantly cleared both drugs (mean ClCVVHDF: ATM 1.28 L/h, AVI 2.08 L/h). Notably, the Oxiris filter produced substantially lower trough concentrations than HF12, suggesting filter type affects exposure. In slow renal recovery, the standard severe impairment dosing sufficed; in rapid recovery, timely TDM-guided dose escalation prevented underdosing.

CONCLUSIONS

ATM-AVI is efficiently cleared by CVVHDF, with filter type influencing drug levels. During AKI recovery, dosing should be adjusted according to the pace of renal function improvement, and therapeutic drug monitoring is essential to guide individualisation.