Intravenous Fosfomycin in hospitalized patients with complicated urinary tract infections due to Third-generation cephalosporinresistant Enterobacterales

INTERVENTION: Pharmaceutical Form: Powder for infusion INN or Proposed INN: FOSFOMICINA CAS Number: 23155‐02‐4 Current Sponsor code: IMP‐1 Other descriptive name: Fosfomycin Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 40‐ CONDITION: Therapeutic area: Diseases [C] ‐ Bacterial Infections and Mycoses [C01] urinary tract infections ; MedDRA version: 20.0 Level: LLT Classification code 10046849 Term: UTI symptoms System Organ Class: 100000004862 PRIMARY OUTCOME: Main Objective: To investigate the non‐inferiority of IV fosfomycin compared to the best available therapy according to current clinical practice/choice Primary end point(s): Clinical Response (CR) defined as clinical and microbiological cure (CMC) at 5 to 7 days after finalization of treatment (test of cure, TOC) Secondary Objective: i) to describe the MIC distribution of isolates against all the study drugs by gold standard methods (i.e. agar dilution for fosfomycin and broth microdilution for alternative drugs) and investigate their correlation with clinical outcome;; ii) to describe the main mechanisms of cephalosporin resistance in the isolates obtained from the blood cultures of patients with bacteremic cUTI by whole genome sequencing (WGS) and analyze their correlation with clinical outcome; iii) to investigate the impact of PK/PD target attainment with clinical outcome;; iv) to evaluate changes in the gut microbiota in patients with cUTIs and to compare the impact of each type of antibiotic therapy on the gut microbiota. Fecal microbial DNA will be extracted and subsequently analyzed by sequencing of the V3‐V4 regions of the 16S ribosomal RNA gene. Timepoint(s) of evaluation of this end point: 5 to 7 days after finalization of treatment INCLUSION CRITERIA: cUTI, in adult patients, defined as the presence of signs or symptoms, pyuria, and growth of cephalosporin‐non‐susceptible, fosfomycin susceptible Enterobacterales in urine (a positive urine culture of 105 colony‐forming units (CFU)/ml). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 185 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 185