A descriptive pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam in a case series of critically ill renal patients treated for documented carbapenem-resistant Gram-negative bloodstream infections and/or ventilator-associated pneumonia

Objectives: To describe the pharmacokinetic/pharmacodynamic (PK/PD) behaviour of continuous infusion (CI) ceftazidime-avibactam and the microbiological outcome in a case series of critically ill renal patients treated for documented carbapenem-resistant Gram-negative (CR-GN) bloodstream infections (BSI) and/or ventilator-associated pneumonia (VAP).Methods: Critically ill patients with different degrees of renal function who were treated with CI ceftazidime-avibactam for documented CR-GN infections, and who underwent therapeutic drug monitor -ing from April 2021 to March 2022, were retrospectively assessed. Ceftazidime and avibactam concentra-tions were determined at steady-state, and the free fraction (fCss) was calculated. The joint PK/PD target of ceftazidime-avibactam was considered as optimal when both Css/MIC ratio for ceftazidime >= 4 (equiv-alent to 100%fT >4xMIC) and Css/CT ratio for avibactam > 1 (equivalent to 100% fT> CT of 4.0 mg/L) were simultaneously achieved (quasi-optimal if only one of the two was achieved, and suboptimal if neither of the two was achieved). The relationship between ceftazidime-avibactam PK/PD targets and microbiologi-cal outcome was assessed.Results: Ten patients with documented CR-GN infections (5 BSIs, 4 VAP, 1 BSI + VAP) were retrieved. The joint PK/PD targets of ceftazidime-avibactam were optimal and quasi-optimal in eight and two cases, respectively. Microbiological failure occurred in two patients (one with VAP, one with BSI + VAP), one of whom developed ceftazidime-avibactam resistance. Both underwent renal replacement therapy, and failed despite attaining optimal joint PK/PD target and receiving fosfomycin co-treatment.Conclusion: CI administration may enable optimal joint PK/PD targets of ceftazidime-avibactam to be achieved in most critical renal patients with CR-GN infections, and may help to minimize the risk of microbiological failure.(c) 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.