UROPOT Trial: Investigating Metabolism-Based Antibiotic Prophylaxis in Endourological Procedures

Key Insights

• The UROPOT trial is a phase I/II randomized, double-blind study evaluating metabolism-based antibiotic prophylaxis in patients undergoing endourological procedures.
• The trial compares low-dose amikacin potentiated with mannitol against standard amikacin and ceftriaxone regimens to reduce postoperative infections.
• Primary outcome is the rate of postoperative infections 48 hours postoperatively, with secondary endpoints including microbiological eradication and pharmacokinetic parameters.

The University Hospital of Lausanne, Switzerland, is conducting the UROPOT trial, a phase I/II randomized, double-blind study to assess the efficacy and safety of metabolism-based antibiotic prophylaxis in patients undergoing endourological procedures. The trial, registered with ClinicalTrials.gov (NCT number not available), focuses on individuals with asymptomatic E. coli and/or K. pneumoniae bacteriuria requiring endourological interventions.

Trial Design and Objectives

The UROPOT trial aims to determine if a lower dose of amikacin, when combined with mannitol, can effectively prevent postoperative infections compared to standard antibiotic prophylaxis regimens. The study addresses the growing concern of antibiotic resistance and seeks to optimize antibiotic usage in a population frequently exposed to prophylactic antibiotics.

Study Arms and Interventions

Participants are randomized into one of three treatment arms:

1. Amikacin (500 mg, approximately 7.5 mg/kg) + Mannitol (5 g): Aims to reduce toxicity by decreasing the aminoglycoside dosing.
2. Amikacin (1000 mg, approximately 15 mg/kg): Standard antibiotic prophylaxis for endourological treatments.
3. Ceftriaxone (2 g intravenously): Standard of care antibiotic prophylaxis in Switzerland.

The interventions are administered as a single infusion over 30 minutes. The primary outcome is the rate of postoperative infections within 48 hours postoperatively, defined by systemic symptoms and positive urine/blood cultures matching preoperative cultures.

Endpoints and Assessments

Secondary outcomes include:

• Microbiological eradication via anti-biofilm activity.
• Sustained microbiological eradication at postoperative days 2 and 14.
• Pharmacokinetic parameters of mannitol and antibiotics in blood and urine samples.

Safety is monitored through the incidence of adverse events, including ototoxicity and nephrotoxicity, and postoperative complications assessed using the Clavien-Dindo classification.

Patient Population and Recruitment

The trial includes patients with asymptomatic E. coli and/or K. pneumoniae bacteriuria undergoing endourological procedures. Key inclusion criteria are bacteriuria defined as ≥102 CFU/ml for both E. coli and K. pneumoniae. Exclusion criteria include the use of antibiotics immediately prior to or during the trial.

Statistical Analysis

Fisher’s exact test will be used to compare the proportions of postoperative infections between the low-dose amikacin + mannitol arm versus the full-dose amikacin arm and the ceftriaxone arm. Microbiological eradication will be compared using t-tests. Mixed-effects models will analyze sustained microbiological eradication. Primary pharmacokinetic parameters will also be calculated.

Addressing Antibiotic Resistance

The UROPOT trial is designed to evaluate whether a metabolism-based approach to antibiotic prophylaxis can maintain efficacy while reducing the overall antibiotic load, thereby mitigating the risk of antibiotic resistance. The study's findings could influence clinical practice by providing evidence for optimized prophylaxis strategies in endourological procedures.