A descriptive pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam for treating DTR gram-negative infections in a case series of critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF)

Milo Gatti; Matteo Rinaldi; Paolo Gaibani; Antonio Siniscalchi; Tommaso Tonetti; Maddalena Giannella; Pierluigi Viale; Federico Pea

doi:10.1016/j.jcrc.2023.154301

A descriptive pharmacokinetic/pharmacodynamic analysis of continuous infusion ceftazidime-avibactam for treating DTR gram-negative infections in a case series of critically ill patients undergoing continuous veno-venous haemodiafiltration (CVVHDF)

J Crit Care. 2023 Aug:76:154301. doi: 10.1016/j.jcrc.2023.154301. Epub 2023 Apr 12.

Authors

Milo Gatti¹, Matteo Rinaldi², Paolo Gaibani³, Antonio Siniscalchi⁴, Tommaso Tonetti⁵, Maddalena Giannella², Pierluigi Viale², Federico Pea⁶

Affiliations

¹ Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. Electronic address: milo.gatti2@unibo.it.
² Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
³ Operative Unit of Microbiology, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁴ Division of Anesthesiology, Department of Anesthesia and Intensive Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁵ Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Anesthesia and Intensive Care Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁶ Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

PMID: 37059003
DOI: 10.1016/j.jcrc.2023.154301

Abstract

Purpose: To explore pharmacokinetic/pharmacodynamic (PK/PD) profile of continuous infusion (CI) ceftazidime-avibactam for treating difficult-to-treat resistant Gram-negative (DTR-GN) infections in critical patients undergoing continuous venovenous haemodiafiltration (CVVHDF).

Materials and methods: Patients treated with CI ceftazidime-avibactam for DTR-GN infections during CVVHDF were retrospectively assessed. Ceftazidime and avibactam concentrations were measured at steady-state and the free fraction (fC_ss) was calculated. Total clearance (CL_tot) of both agents were calculated and the impact of CVVHDF intensity was assessed by linear regression. The joint PK/PD target of ceftazidime-avibactam was defined as optimal when both fC_ss/MIC≥4 for ceftazidime and fC_ss/C_T > 1 for avibactam were achieved. Relationship between ceftazidime-avibactam PK/PD targets and microbiological outcome was assessed.

Results: Eight patients with DTR-GN infections were retrieved. Median fC_ss were 84.5 (73.7-87.7 mg/L) for ceftazidime and 24.8 mg/L (20.7-25.8 mg/L) for avibactam. Median CL_tot was 2.39 L/h (2.05-2.96 L/h) for ceftazidime and 2.56 L/h (2.12-2.98 L/h) for avibactam. Median CVVHDF dose was 38.6 mL/h/kg (35.9-40.0 mL/kg/h). CL_tot were linearly correlated with CVVHDF dose (r = 0.53;p = 0.03, and r = 0.64;p = 0.006, respectively). The joint PK/PD targets were optimal granting microbiological eradication in all the assessable cases.

Conclusion: CI administration of 1.25-2.5 g q8h ceftazidime-avibactam may allow prompt attainment and maintenance of optimal joint PK/PD targets during high-intensity CVVHDF.

Keywords: Ceftazidime-avibactam; Continuous infusion; Continuous renal replacement therapy; Continuous venovenous haemodiafiltration; DTR gram-negative infections; Joint PK/PD target attainment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents
Ceftazidime* / pharmacology
Ceftazidime* / therapeutic use
Continuous Renal Replacement Therapy*
Critical Illness / therapy
Humans
Microbial Sensitivity Tests
Retrospective Studies

Substances

avibactam, ceftazidime drug combination
Ceftazidime
Anti-Bacterial Agents
avibactam