Severe Sepsis
Conditions
Keywords
Severe sepsis, Ceftazidime-avibactam, Plasma drug concentration, Population pharmacokinetics (PPK), Pharmacokinetic (PK), Critically ill Patients, Pharmacodynamic (PD)
Brief summary
A observational study is conducting at the First Affiliated Hospital of the Medical College of Zhejiang University from June 1, 2021 to January 1, 2024. Patients with severe sepsis and treatment with Ceftazidime-avibactam (CAZ-AVI) will be enrolled. Blood samples at different time points: 0 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the first time and the steady state concentration(more than 4 times drug administration) of drug administration will be collected to detect plasma drug concentrations of CAZ-AVI.
Detailed description
The investigators will collect the blood samples at different time points: 0 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the first time and the steady state concentration(more than 4 times drug administration) of drug administration from the patients receive treatment with CAZ-AVI to detect plasma drug concentrations of CAZ-AVI. The collected specimens will be stored in a refrigerator at 0-8 °C, centrifuges within 24 hours (4 °C, 4000 r/min, 10 min), and the supernatant will be collected in an EP tube and stored at -80°C until subsequent analysis. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) will be used to detect plasma drug concentrations of CAZ-AVI. According to the outcomes ,the investigators will characterize the population pharmacokinetics (PPK) of CAZ-AVI in critically ill patients and performed pharmacodynamic target attainment analyses to determine optimal dosing regimens for patients with and without continuous renal replacement therapy (CRRT).
Interventions
Patients with severe sepsis and treatment with CAZ-AVI will be enrolled. Blood samples at 0 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the first time and the steady state concentration(more than 4 times drug administration) of drug administration will be collected to detect plasma drug concentrations of CAZ-AVI
Sponsors
First Affiliated Hospital of Zhejiang University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with severe sepsis and treated with ceftazidime avibactam * Age ≥ 18 years * The patient or authorized persons agree and sign the informed consent * The patient's hemoglobin is greater than 70g/l during blood collection
Exclusion criteria
* The expected length of ICU stay less than 48 hours, * Pregnant woman, * The blood sample is hemolysis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma drug concentrations of CAZ-AVI | 0 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the first time of drug administration | Plasma drug concentrations of CAZ-AVI after the first time of drug administration |
| A population pharmacokinetic (PopPK) model for CAZ-AVI and to propose an appropriate dosing regimen in Chinese critically ill patients. | After obtaining the patient's plasma drug concentration | By conducting pharmacokinetic and pharmacodynamic analysis on the plasma drug concentration data of patients receiving CAZ-AVI treatment in the intensive care unit, we aim to develop a population pharmacokinetic (PopPK) model for critically ill patients in China and to formulate an appropriate dosing regimen for critically ill patients with varying degrees of renal function, including those undergoing renal replacement therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The level of glomerular filtration rate | The day of the first time of drug administration | The level of glomerular filtration rate on the day of the first time of drug administration |
| Whether received renal replacement therapy | The day of the first time of drug administration | Whether the patient received renal replacement therapy on the day of the first time of drug administration, and the results are recorded in the form of categorical variables,(e.g.,yes or no). |
| Respiratory function | The day of the first time of administration | Whether the patient received mechanical ventilation on the day of the first time of drug administration, and the results are recorded in the form of categorical variables,(e.g.,yes or no). |
| Cardiovascular function | The day of the first time of drug administration | Whether the patient received vasoactive agents(including norepinephrine, epinephrine, dobutamine, and metarylamine), and the results are recorded in the form of categorical variables,(e.g.,yes or no). |
| Serum albumin | The day of the first time of drug administration | The level of serum albumin on the day of the first time of drug administration |
| microbiological clearance, infection-related mortality | 14 day after the onset of infection | microbiological clearance, 14 day infection-related mortality, |
| all-cause mortality | 30 day and 90 day after the onset of infection | 30 day all-cause mortality,90 day all-cause mortality |
| length of stay | Day 1 is defined as the day of confirmed diagnosis, the duration from confirmed diagnosis to ICU discharge will be measured. | Post-infection ICU length of stay |
| CRRT treatment dosage | The day of the first time of drug administration | The specific parameters for patients undergoing CRRT include the type of CRRT machine, treatment modality, treatment method, filter type, treatment duration, pre-dilution volume, post-dilution volume, blood pump flow rate, dialysis pump flow rate, average hourly fluid removal, treatment dose, ultrafiltration rate, and waste fluid volume |
| The level of creatinine | The day of the first time of drug administration | The level of creatinine on the day of the first time of drug administration |
Countries
China
Outcome results
None listed