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 monitoring from April 2021 to March 2022, were retrospectively assessed. Ceftazidime and avibactam concentrations 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 (equivalent 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 microbiological 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.

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

Gatti, Milo;Pascale, Renato;Cojutti, Pier Giorgio;Rinaldi, Matteo;Ambretti, Simone;Tedeschi, Sara;Giannella, Maddalena;Viale, Pierluigi;Pea, Federico
2023

Abstract

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 monitoring from April 2021 to March 2022, were retrospectively assessed. Ceftazidime and avibactam concentrations 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 (equivalent 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 microbiological 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.
2023
Gatti, Milo; Pascale, Renato; Cojutti, Pier Giorgio; Rinaldi, Matteo; Ambretti, Simone; Conti, Matteo; Tedeschi, Sara; Giannella, Maddalena; Viale, Pierluigi; Pea, Federico
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/914534
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