Clinical Study on Monitoring the Plasma Concentration of Ceftazidime-Avibactam in Critically Ill Patients

This prospective observational study is conducted at the First Affiliated Hospital of Zhejiang University School of Medicine from June 1, 2021 to January 1, 2024. The study aims to characterize the population pharmacokinetics of ceftazidime (CAZ) and avibactam (AVI) in critically ill patients receiving ceftazidime-avibactam (CAZ-AVI), including patients with and without renal replacement therapy (RRT). Plasma concentrations of CAZ and AVI will be measured after the first-dose and steady-state administrations. Population pharmacokinetic and pharmacokinetic/pharmacodynamic target-attainment analyses will be performed to explore dosing strategies according to renal function and RRT status.

Study Overview

• Status: Completed
• Conditions: Severe Sepsis; Carbapenem Resistant Bacterial Infection
• Intervention / Treatment: Drug: Ceftazidime-avibactam

Detailed Description

This is a prospective, single-center observational cohort study of critically ill adult patients receiving CAZ-AVI for carbapenem-resistant organism (CRO) infections. Arterial blood samples (3 mL) will be collected at 0, 1, 2, 4, 6, and 8 hours after the first-dose and steady-state CAZ-AVI infusions. Blood samples will be centrifuged at 4°C and 4000 rpm for 10 min, and the separated plasma will be stored at -80°C until measurement of ceftazidime (CAZ) and avibactam (AVI) concentrations. Plasma concentrations of CAZ and AVI will be quantified using ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF). Clinical and laboratory characteristics will be recorded, together with RRT-related treatment parameters in patients receiving RRT. Population pharmacokinetic(PPK) models of CAZ and AVI will be developed using the collected concentration and clinical data.The resulting PPK models will subsequently be used in Monte Carlo simulations (MCSs) to identify candidate model-informed dosing regimens across renal-function and RRT strata.

• Study Type: Observational
• Enrollment (Actual): 33

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The First Affiliated Hospital,College of Medicine,Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will comprise critically ill adult patients receiving ceftazidime-avibactam (CAZ-AVI) for carbapenem-resistant organism (CRO) infections at the intensive care unit of the First Affiliated Hospital, Zhejiang University School of Medicine.

Description

Inclusion Criteria:

• Critically ill patients with severe sepsis(CRO infections) and treated with CAZ-AVI(culture-confirmed CRO susceptible to CAZ-AVI);
• Age ≥ 18 years;
• Expected ICU stay ≥48 hours.
• Hemoglobin >70 g/L during the pharmacokinetic blood-sampling period；
• The patient or authorized persons agree and sign the informed consent.

Exclusion Criteria:

• Expected ICU stay <48 hours.
• Pregnant woman.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma drug concentrations of CAZ and AVI after first-dose administration	Plasma concentrations of CAZ and AVI will be measured after the first-dose infusion.	0, 1, 2, 4, 6, and 8 hours after the first-dose infusion.
Plasma drug concentrations of CAZ and AVI at steady state	Plasma drug concentrations of CAZ and AVI will be measured after the steady-state infusion	0, 1, 2, 4, 6, and 8 hours after the steady-state infusion.
Population pharmacokinetic characterization and PK/PD-based dosing evaluation of CAZ-AVI	Population pharmacokinetic models of ceftazidime and avibactam will be developed using plasma concentration and clinical data from critically ill patients. Pharmacokinetic/pharmacodynamic analyses will be performed to evaluate dosing regimens across different levels of renal function, including patients receiving renal replacement therapy (RRT).	After completion of pharmacokinetic data collection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
length of stay	Post-infection ICU length of stay	Day 1 is defined as the day of confirmed diagnosis, the duration from confirmed diagnosis to ICU discharge will be measured.
length of stay	Total ICU length of stay.	From ICU admission to ICU discharge will be measured(assessed up to 120 days).
Microbiological clearance	Microbiological clearance assessed based on follow-up microbiological culture results.	14 day after the onset of infection
Infection-related mortality	Infection-related mortality within 14 days after the onset of infection.	14 day after the onset of infection
Treatment outcome	Treatment outcome within 14 days after the onset of infection.	14 day after the onset of infection
all-cause mortality	30 day all-cause mortality	30 day after the onset of infection

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Investigators: Study Chair: YongHong Xiao, PhD, First affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): September 8, 2023
• Study Completion (Actual): December 20, 2023

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 7, 2022
• First Posted (Actual): June 10, 2022

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Renal replacement therapy; Severe sepsis; Ceftazidime-avibactam; Pharmacokinetic (PK); Critically ill Patients; Pharmacodynamic (PD); Population pharmacokinetics (PPK)
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis; Third Generation Cephalosporins; Beta Lactam Antibiotics; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; beta-Lactamase Inhibitors; avibactam, ceftazidime drug combination
• Other Study ID Numbers: 2022-468

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Respect ethics and protect patient privacy

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No