Study of the Pharmacokinetics of Ceftriaxone (Etude PC-IUU)

Study of the Pharmacokinetics of Ceftriaxone in Urinary Tract Infections in the Emergency Department

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.

Study Overview

• Status: Terminated
• Conditions: Urinary Infections
• Intervention / Treatment: Biological: free ceftriaxone concentration dosage

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.

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• France
  • Rouen, France, 76031
    • Rouen University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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).

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the probability of reaching the efficiency threshold fT > 1x MIC = 100% for MICs varying from 0.25 to 32 mg/L	For beta-lactams (BL) such as ceftriaxone, this is the fraction of time, fT, (expressed as a percentage between doses) where the free concentration of the antibiotic is above the minimum inhibitory concentration or MIC (%ƒT>MIC). - The probability of reaching the efficacy threshold fT > 1x MIC = 100% will be assessed using PTA (probability of target attainment) curves. Simulations will be performed using the pharmacokinetic model with different dosages and according to different MICs (from 0 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	The relationship between the free and total form of plasma ceftriaxone will be studied according to a linear binding model	within 24 hours after enrollment visit
Describe the microbial epidemiology of UTIs in the Emergency Department (ED)	The microbial epidemiology of UTIs in the ED will be assessed by microbiological analysis of the ECBU of included patients collected retrospectively.	within 24 hours after enrollment visit
Determine the impact of clinical-biological variables on the pharmacokinetic profile of ceftriaxone (weight)	The weight will be that measured from the patient. This variable will be analyzed centered on the mean with and without logarithmic conversion.	within 24 hours after enrollment visit
Determine the impact of clinical-biological variables on the pharmacokinetic profile of ceftriaxone (albuminemia)	The dosages of albuminemia will be carried out using samples taken as part of the study. The variable will be analyzed centered on the mean with and without logarithmic conversion.	within 24 hours after enrollment visit
Determine the impact of clinical-biological variables on the pharmacokinetic profile of ceftriaxone (bilirubinemia)	The dosages of bilirubinemia will be carried out using samples taken as part of the study. The variable will be analyzed centered on the mean with and without logarithmic conversion.	within 24 hours after enrollment visit
Determine the impact of clinical-biological variables on the pharmacokinetic profile of ceftriaxone (creatinineemia)	The dosages of creatinineemia will be carried out using samples taken as part of the study. The variable will be analyzed centered on the mean with and without logarithmic conversion.	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	The relationship between the free and total form of plasma ceftriaxone will be studied according to an empirical saturation model	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	The relationship between the free and total form of plasma ceftriaxone will be studied according to different in vivo saturation models	within 24 hours after enrollment visit

Collaborators and Investigators

• Sponsor: University Hospital, Rouen

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2024
• Primary Completion (Actual): November 30, 2025
• Study Completion (Actual): December 30, 2025

Study Registration Dates

• First Submitted: September 1, 2025
• First Submitted That Met QC Criteria: September 9, 2025
• First Posted (Actual): September 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: pharmacokinetics; antibiotic; therapeutic target; cephalosporin
• Other Study ID Numbers: 2023/212/OB; 2023-A02238-37 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data provided will be the property of the sponsor and will be used solely for its own research activities.

Drug and device information, study documents

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