Potentiated Aminoglycosides in Postoperative Urinary Tract Infection Prophylaxis

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).

Inclusion Criteria:Written informed consentAdults (≥18 years)Ureteral stent in situPatients 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 mannitolPregnant and lactating womenGlomerular filtration rate (CKD-EPI eGFR) < 50ml/min / 1,73m2Hearing impairmentMyasthenia gravis or other forms of myoneural disordersCongestive heart failure, Pulmonary edemaIntracranial hemorrhage, blood-brain barrier compromisePrevious (within 3 months prior to randomization) or concomitant participation in another interventional clinical trialAntibiotic treatment within 14 days prior to randomizationMixed cultures of E. coli and/or K. pneumonia with other bacteriaInability to understand and follow the protocolInability to give informed consentBMI<20 or >30