Metabolic Potentiation of Aminoglycosides: a Novel Antimicrobial Strategy to Prevent Urinary Tract Infections (UROPOT TRIAL).

UROPOT is a randomized, single-centre, double-blind, pilot trial comparing a combination of aminoglycosides and mannitol to standard of care or aminoglycosides alone for the peri-operative antimicrobial prophylaxis of endourological procedures with mucosal trauma in the presence of hardware. Adults (≥18 years) scheduled for such procedures with mucosal trauma (stone surgery with hardware, pig-tail catheter exchanges) and having an asymptomatic bacteriuria E. coli or K. pneumoniae as identified 10 days prior to surgery, will be randomly assigned (1:1:1) to receive standard prophylaxis (gen. Ceftriaxone 2 g) for 24 hours, a single dose of amikacin (6mg/kg i.v.) or a single dose of mannitol (pres. 2.5g i.v. bolus)/amikacin (3mg/kg i.v.). Sample size for the three groups will be constructed to demonstrate a non-inferiority for the clinical outcome (absence of infectious complication within 48 hours from operation) with a power of 80%. Complications in the absence of antimicrobial prophylaxis range from 2-10%. Patients will be excluded if baseline urine culture has another bacterial pathogen or E. coli or K. pneumoniae are documented to be aminoglycoside resistant. The primary endpoint will be the prevention of complications(clinical) that will be evaluated for non-inferiority compared to the accepted standard of care. i.e., within a 6% margin Assuming a rate of complication as low as 2%, the new treatments will be considered non-inferior if the corresponding rate of complication is not above 8% (i.e., 6% margin). This non-inferiority margin can be evaluated with a total for 128 patients per treatment arm, at 1-sided alpha of 5%, with power 80%, through an exact two-sample test for proportions. Two comparisons will be performed of arm A and of arm B versus standard of care (SoC). In addition, a microbiological outcome will be included to document higher biofilm eradication rate. This will be documented by sonication of extracted hardware as well as repeat urine culture at post-operative days 7 and 14 days (secondary outcomes). Safety will be monitored with a specific focus on nephrotoxicity and ototoxicity. If highly efficient, this novel antimicrobial strategy would be expanded to treatment of complicated urinary tract infections.