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Ceftazidime-avibactam is a β-lactam/β-lactamase inhibitor combination treatment which has been developed to address infections caused by ESBL-, AmpC- and serine carbapenemase-producing Gram-negative bacteria. In elderly patients, significant interindividual variability often leads to inappropriate dosing (subtherapeutic or excessive), compromising efficacy or increasing toxicity risks. This prospective, multicenter study will enroll patients aged ≥60 years receiving ceftobiprole. Using LC-MS/MS for therapeutic drug monitoring (TDM), we will measure plasma concentrations and integrate individual characteristics (age, body weight, creatinine clearance, etc.). Population pharmacokinetic (PPK) modeling with Bayesian forecasting will be employed to estimate individual PK parameters and identify covariates influencing variability, thereby establishing a PPK model for ceftazidime-avibactam in the elderly.
Based on pathogen-specific MIC values, dosing regimens (dose, frequency) will be dynamically optimized to guide precision therapy. Subsequent TDM data will continuously refine the PPK model, creating a self-optimizing system. This framework lays the groundwork for extending individualized treatment strategies to other antimicrobials in geriatric populations.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ceftazidime-avibactam | Clinical Blood Sampling Protocol for Ceftazidime-avibactam in Geriatric Patients: Elderly patients received intravenous ceftobiprole, with infusion durations of 1h, 1.5h, or 2h. After 3days of antibiotic therapy (steady-state achievement), blood sampling was performed as follows: Trough Concentration: A 3mL peripheral blood sample was collected from the antecubital vein pre-dose (before the next scheduled administration) using EDTA-containing Vacutainers®. Peak Concentration: A blood sample was drawn immediately after completion of the intravenous infusion. All blood specimens were centrifuged at 2500×g for 10 minutes. Plasma samples were stored at -20℃ and analyzed within 1 week of collection via liquid chromatography-tandem mass spectrometry (LC-MS/MS). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| liquid chromatography-tandem mass spectrometry | Diagnostic Test | Quantitative determination of ceftazidime-avibactam concentrations in plasma and urine was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). |
| Measure | Description | Time Frame |
|---|---|---|
| Ceftazidime-avibactam Concentration | Plasma Ceftobiprole Concentration and Urinary Ceftazidime-avibactam Concentration | after 3 days of antibiotic therapy |
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Inclusion Criteria:
Exclusion Criteria:
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Professional Translation for Clinical Research Protocols: Enroll patients aged ≥60 years receiving ceftazidime-avibactam therapy at Chinese PLA General Hospital
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yaping Yuan Clinical Professor | Contact | 010-876250 | yuanyp301@163.com |
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