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: Not yet recruiting
• Conditions: Ceftazidime-avibactam
• Intervention / Treatment: Diagnostic test: liquid chromatography-tandem mass spectrometry

• Study Type: Observational
• Enrollment (Estimated): 150

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: Yes

• Sampling Method: Non-Probability Sample

Study Population

Professional Translation for Clinical Research Protocols: Enroll patients aged ≥60 years receiving ceftazidime-avibactam therapy at Chinese PLA General Hospital

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?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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).

Diagnostic test: liquid chromatography-tandem mass spectrometry; 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	Plasma Ceftobiprole Concentration and Urinary Ceftazidime-avibactam Concentration	after 3 days of antibiotic therapy

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 25, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: March 21, 2026
• First Submitted That Met QC Criteria: March 21, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 21, 2026
• Last Verified: March 1, 2026

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)?: NO

Drug and device information, study documents

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