Potentiated Aminoglycosides in Postoperative Urinary Tract Infection Prophylaxis

• Status: Not yet recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Urinary tract hardware such as pig-tail catheters are are frequently used for management of urolithiasis or other obstructive pathologies. They are readily colonized by urogenital flora leading to asymptomatic bacteriuria. While asymptomatic bacteriuria is not per se a problem for patients, it may lead to severe infections in the context of hardware manipulation leading to mucosal damage (e.g. catheter exchanges or stone extraction). Such interventions therefore warrant an antibiotic prophylaxis. However, bacteria rapidly form biofilms on hardware; aside of fluoroquinolones, antibiotics have limited anti-biofilm activity. Furthermore, the widespread use of antibiotics has lead to resistant strains. Hence, novel antimicrobial strategies are needed. Recently, metabolism-based potentiation of aminoglycoside has shown high antimicrobial activity against persistent forms of bacteria such as biofilms in the context of murine catheter-associated urinary tract infections. Because of the highly favorable pharmacodynamic profile of aminoglycoside in the urinary tract and the metabolic potentiation, aminoglycosides can be reduced to levels with minimal toxicity.

UROPOT aims to compare the efficacy of potentiated aminoglycoside to standard of care for (i) prophylaxis of asymptomatic bacteriuria during urinary hardware manipulations with mucosal trauma (Pig-tail catheter exchange, stone surgery with prior in-dwelling catheter, etc.) and (ii) sustained microbiological eradication through antibiofilm activity. UROPOT will compare the rate of post-interventional urinary tract infections (primary outcome). It will also assess safety and eradication potency (microbiological outcome).

• Phase: Early Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Hospitalier Universitaire Vaudois
• Collaborators: Ecole Polytechnique Fédérale de Lausanne; University Hospital Inselspital, Berne
• Treatments: Amikacin; Ceftriaxone; Mannitol

Criteria

Inclusion Criteria:

• Written informed consent

• Adults (≥18 years)

• Ureteral stent in situ

• Patients scheduled for endourological ureteral manipulations (e.g. endourological stone surgery, ureteral stent exchange)

• Asymptomatic bacteriuria with strains of E. coli and/or K. pneumoniae sensitive to Ceftriaxone and Amikacin/Aminoglycosides.

Exclusion Criteria:

• Allergy to one of the study drugs Beta-lactams, aminoglycosides or mannitol

• Pregnant and lactating women

• Glomerular filtration rate (CKD-EPI eGFR) < 50ml/min / 1,73m2

• Hearing impairment

• Myasthenia gravis or other forms of myoneural disorders

• Congestive heart failure, Pulmonary edema

• Intracranial hemorrhage, blood-brain barrier compromise

• Previous (within 3 months prior to randomization) or concomitant participation in another interventional clinical trial

• Antibiotic treatment within 14 days prior to randomization

• Mixed cultures of E. coli and/or K. pneumonia with other bacteria

• Inability to understand and follow the protocol

• Inability to give informed consent

• BMI<20 or >30