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

Study Overview
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Brief Summary
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A observational study is conducting at the First Affiliated Hospital of the Medical College of Zhejiang University from January 1, 2022 to January 1, 2024. Patients with severe sepsis and treatment with Ceftazidime-Avibactam will be enrolled. Blood samples at different timepoints: 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 ceftazidime avibactam.

Detailed Description
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The investigators will collect the blood samples at different timepoints: 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 Ceftazidime-Avibactam to detect plasma drug concentrations of ceftazidime avibactam. 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 ceftazidime avibactam. According to the outcomes ,the investigators will analyze the following items,(1)T>MIC,(2)Cmax/MIC,(3)AUC/MIC,(4)population pharmacokinetics.

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

Conditions
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Severe Sepsis

Intervention / Treatment
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* Drug: Ceftazidime-avibactam


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ceftazidime-avibactam|Patients with severe sepsis and treatment with Ceftazidime-Avibactam 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 ceftazidime avibactam.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma drug concentrations of ceftazidime avibactam | Plasma drug concentrations of ceftazidime avibactam after the first time of drug administration | 0 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the first time of drug administration | 
| Plasma drug concentrations of ceftazidime avibactam | Plasma drug concentrations of ceftazidime avibactam after the steady state concentration (more than 4 times drug administration) of drug administration | 0 hour, 2 hours, 4 hours, 6 hours, and 8 hours after the steady state concentration (more than 4 times drug administration) of drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum albumin | The level of serum albumin on the day of the first time of drug administration | The day of the first time of drug administration | 
| Serum albumin | The level of serum albumin on the day of the steady state concentration(more than 4 times drug administration) of drug administration | The day of the steady state concentration (more than 4 times drug administration) of drug administration | 
| The level of creatinine | The level of creatinine on the day of the first time of drug administration | The day of the first time of drug administration | 
| The level of creatinine | The level of creatinine on the day of the steady state concentration(more than 4 times drug administration) of drug administration | The day of the first time of the steady state concentration (more than 4 times drug administration) of drug administration | 
| The level of glomerular filtration rate | The level of glomerular filtration rate on the day of the first time of drug administration | The day of the first time of drug administration | 
| The level of glomerular filtration rate | The level of glomerular filtration rate on the day of the steady state concentration (more than 4 times drug administration) of drug administration | The day of the steady state concentration (more than 4 times drug administration) of drug administration | 
| Whether received renal replacement therapy | 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). | The day of the first time of drug administration | 
| Whether received renal replacement therapy | Whether the patient received renal replacement therapy on the day of the steady state concentration (more than 4 times drug administration) of drug administration, and the results are recorded in the form of categorical variables,(e.g.,yes or no). | The day of the steady state concentration (more than 4 times drug administration) of drug administration | 
| Respiratory function | 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). | The day of the first time of administration | 
| Respiratory function | Whether the patient received mechanical ventilation on the day of the steady state concentration (more than 4 times drug administration) of drug administration, and the results are recorded in the form of categorical variables,(e.g.,yes or no). | The day of the steady state concentration (more than 4 times drug administration) of drug administration | 
| Cardiovascular function | 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). | The day of the first time of drug administration | 
| Cardiovascular function | 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). | The day of the steady state concentration (more than 4 times drug administration) of drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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severe sepsis, ceftazidime avibactam, plasma drug concentration