Study of the Pharmacokinetics of Ceftriaxone

NCT07169097 | Recruiting

• 2 other identifiers: 2023/212/OB2023-A02238-37
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Urinary tract infections (UTIs) are the leading cause of community-acquired bacterial infections in adults. They are a common reason for admission to the Emergency Department (ED), particularly when pyelonephritis is suspected. The main bacteria responsible for UTIs are Enterobacteriaceae, with Escherichia coli being the main cause, found in more than 90% of cases. The French guidelines of the SPLIF (French-Speaking Infectious Pathology Society) recommend the probabilistic use of a 3rd generation cephalosporin or a fluoroquinolone. Ceftriaxone is often chosen over cefotaxime because it can be injected only once a day, which simplifies its administration in overcrowded emergency departments. There are currently no SPLIF recommendations regarding the dosage of ceftriaxone to be administered. The IDSA (Infectious Diseases Society of America) suggests a single dosage of 1 gram/day. Ceftriaxone is a 3rd generation cephalosporin antibiotic in the β-lactam class. Its mechanism of action is based on the inhibition of bacterial cell wall synthesis. Due to its broad spectrum against Gram-positive and Gram-negative aerobic bacteria and also some anaerobic germs, ceftriaxone is a commonly prescribed antibiotic in emergency departments (Therapeutic Guidelines Limited, Melbourne, 2014; Kumar et al., 2009) because of its broad indications: neuromeningeal infections, intra-abdominal infections and urinary tract infections (UTIs). Since most UTIs requiring hospitalization do not require intensive care, the optimal dosage of ceftriaxone in this context remains to be determined. Indeed, patients in emergency departments are on average less serious, without sepsis or septic shock, and therefore with probably different pharmacokinetic parameters.

Conditions

Urinary Infections

Keywords

antibiotic; cephalosporin; therapeutic target; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with urinary tract infection (UTI) for whom the time spent with a free ceftriaxone concentration

  To determine the proportion of patients with UTI for whom the time spent with a free ceftriaxone concentration above 1x MIC is 100% (fT \> 1x MIC = 100%). The primary objective will be evaluated by simulation using a two-compartment population pharmacokinetic model whose initial parameters will be set in accordance with the scientific literature. The residual concentration of free ceftriaxone will be used and compared to the critical concentration threshold of ceftriaxone for each pathogen defined by EUCAST (European Committee on Antimicrobial Susceptibility Testing).

  within 24 hours after enrollment visit

Secondary Outcomes (9)

• Determine the probability of reaching the efficiency threshold fT > 1x MIC = 100% for MICs varying from 0.25 to 32 mg/L

  within 24 hours after enrollment visit

• Determine a mathematical function allowing the free plasma fraction of ceftriaxone to be extrapolated from the total ceftriaxone concentration

  within 24 hours after enrollment visit

• Describe the microbial epidemiology of UTIs in the Emergency Department (ED)

  within 24 hours after enrollment visit

• Determine the impact of clinical-biological variables on the pharmacokinetic profile of ceftriaxone (weight)

  within 24 hours after enrollment visit

• Determine the impact of clinical-biological variables on the pharmacokinetic profile of ceftriaxone (albuminemia)

  within 24 hours after enrollment visit

Interventions

free ceftriaxone concentration dosage BIOLOGICAL

The proportion of patients with UTI for whom the time spent with a free ceftriaxone concentration above 1x MIC is 100% will be determined by calculating the ratio of the total number of patients meeting this criterion to the total number of patients included. Plasma ceftriaxone dosages will be integrated into a structural model from the scientific literature using the MonolixSuite 2023R1® package (Lixoft - Saclay) including a modeling module (Monolix) and a simulation module (Simulx). T. Individual pharmacokinetic parameters will be determined by Bayesian estimation by integrating the dosage performed in the protocol.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patient (\>18 years) with clinical diagnosis of urinary tract infection requiring antibiotic therapy with ceftriaxone at a dose of 1g/24h intravenously (IV).

You may qualify if:

• Adult patient over 18 years of age
• Requiring hospitalization at Rouen University Hospital
• Clinical diagnosis of urinary tract infection requiring ceftriaxone antibiotic therapy
• Prescription of 1g IV ceftriaxone
• Venipuncture for laboratory testing as part of the prescribed treatment within 24 hours of the first ceftriaxone injection
• Patient has read and understood the information letter and given oral consent to participate in the study

You may not qualify if:

• Minor patient
• Patient hospitalized in an intensive care unit
• Patient with septic shock
• Chronic dialysis or indication for emergency renal replacement therapy (ERP)
• Prescription of a dosage other than 1g intravenously per 24 hours
• Patient having received more than one injection of 1g ceftriaxone
• Pregnant, parturient, or breastfeeding woman
• Person deprived of liberty by an administrative or judicial decision
• Person placed under judicial protection, guardianship, or curatorship

Sponsors & Collaborators

• University Hospital, Rouen: lead

Study Sites (1)

Rouen University Hospital

Rouen, 76031, France

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

A 4 mL dry tube and a 4 mL heparinized tube will be collected for the determination of total and free ceftriaxone, albumin and bilirubin concentration in the blood.

Central Study Contacts

Johnny JM MICHEL, Doctor

CONTACT

02 32 88 68 59; johnny.michel@chu-rouen.fr

Thomas TD DUFLOT, Doctor

CONTACT

02 32 88 56 34; thomas.duflot@chu-rouen.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2025
• First Posted: September 11, 2025
• Study Start: September 30, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)