Study of the Pharmacokinetics of Ceftriaxone

NCT ID: NCT07169097

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2027-05-01

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.

Detailed Description

While PK data in healthy volunteers support a single dose of ceftriaxone 1 gram/day, those from intensive care patients support 2 or even 4 grams/day. Febrile UTIs are a heterogeneous group of patients ranging from simple acute pyelonephritis in young women with no history to complex urinary tract infection in malnourished elderly patients and male urinary tract infection in elderly patients with benign prostatic hyperplasia. The present project therefore aims to evaluate whether a single dose of 1 g of ceftriaxone is sufficient to achieve the therapeutic target in all patients suffering from febrile UTI without septic shock or whether certain situations would justify a dosage adjustment. To this end, patients presenting a clinical and biological picture of UTI and having received ceftriaxone administration will be offered inclusion in this protocol. 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 concentrations. These samples will be added to the assessment performed as part of routine care within 24 hours of the first ceftriaxone injection. This study will calculate the probability of reaching the therapeutic target in patients treated with ceftriaxone for UTI without septic shock. Depending on the results, this study could allow the proposal of a personalized dosage of ceftriaxone for each patient suffering from urinary tract infection based on their clinical and biological parameters.

Conditions

Urinary Infections

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Interventions

free ceftriaxone concentration dosage

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Rouen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Rouen University Hospital

Rouen, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Johnny JM MICHEL, Doctor

Role: CONTACT

johnny.michel@chu-rouen.fr

02 32 88 68 59 ext. +33

Thomas TD DUFLOT, Doctor

Role: CONTACT

thomas.duflot@chu-rouen.fr

02 32 88 56 34 ext. +33

Facility Contacts

Johnny MICHEL, Doctor

Role: primary

johnny.michel@chu-rouen.fr

02 32 88 68 59 ext. +33

Thomas TD DUFLOT, Doctor

Role: backup

thomas.duflot@chu-rouen.fr

02 32 88 56 34 ext. +33

Other Identifiers

2023-A02238-37

Identifier Type: OTHER

Identifier Source: secondary_id

2023/212/OB

Identifier Type: -

Identifier Source: org_study_id