Individualized Precision Therapy With Ceftazidime and Avibactam Guided by PK/PD in Geriatric Populations
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Yaping Yuan Clinical Professor
- Phone Number: 010-876250
- Email: yuanyp301@163.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- Aged ≥60 years Scheduled to receive ceftazidime-avibactam therapy for >5 days No prior ceftazidime-avibactam use within 1 month before enrollment
Exclusion Criteria:
- Patients requiring renal replacement therapy (hemodialysis, peritoneal dialysis, or continuous renal replacement therapy [CRRT]) or with renal impairment history (nephrectomy, renal transplantation, solitary kidney, uremia)
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
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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). |
Quantitative determination of ceftazidime-avibactam concentrations in plasma and urine was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Ceftazidime-avibactam Concentration
Time Frame: after 3 days of antibiotic therapy
|
Plasma Ceftobiprole Concentration and Urinary Ceftazidime-avibactam Concentration
|
after 3 days of antibiotic therapy
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- S2025-448-02
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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