Curative Efficacy of Fosfomycin Tromethamine Versus Ciprofloxacin in the Initial Therapy of Uncomplicated UTI—a Prospective Open-Label Randomised Controlled Clinical Study

Abstract

The precise current role of fosfomycin in the management of uncomplicated UTI (uUTI) is not well defined in the published English literature (PubMed(™)). We aim to compare the overall curative efficacy, safety, and outcome of fosfomycin tromethamine vis-a-vis Ciprofloxacin therapy in the initial management of uncomplicated UTI in a select group of patients. After obtaining prior institutional ethical clearance and written informed consent, 120 consenting patients with uUTI were selected as per protocol (based on symptoms of uUTI, positive urine culture sensitivity (c/s), urine routine/microscopy (r/m) or positive urine leukocyte esterase dipstick (LED) test) and enrolled in this study. They were randomized by computer draw of lots, into two groups of 60 each, randomised to receive initial empirical therapy with either fosfomycin (F-intervention arm) or Ciprofloxacin (C-comparator arm), pending the urine culture report. Patients were followed up with urine culture analysis and other parameters. The primary outcome measures were clinical/bacteriological response/resolution of UTI documented by negative urine culture (sent on day 3), absence of pyuria, and negative urine LED on 3rd day. Urine c/s was sent at day 0, but treatment was started (based on randomization) for those with urine r/m positive and positive LED test, pending the result of c/s. If the urine c/s turned out to be negative, the patient was excluded from the study. For the patients who satisfied the inclusion criteria, urine c/s was again sent on day 3, based on which report, bacteriological cure was defined. Secondary outcomes included bacteriological spectrum, antimicrobial sensitivity pattern, incidence of UTI caused by extended spectrum beta-lactamase (ESBL) producing strains of Escherichia coli, possible risk factors for UTI, side effects, ADRs, and ADEs of the drugs. E. coli and Klebsiella were the commonest cause of UTI while ESBL uropathogens were detected in 14/120 (11.67% 11 and 3 in F/C groups, respectively) patients. The sensitivity of uropathogens to F and C was 86 and 50% respectively while the overall clinical curative efficacy (CCE) of same was 83 and 43% respectively. In the subset of 14 patients with UTI due to ESBL, the CCE of F and C was 91 and 67% respectively. Side effects (minor and self-limiting) were significantly more common with the F group (p < 0.001), with diarrhoea being the commonest. Hospitalization was the commonest risk factor for UTI (27%) though the association of risk factors with UTI was not significantly different (p = 0.609). Fosfomycin was safe and significantly more efficacious in treating uncomplicated UTI (p < 0.001) versus ciprofloxacin. The overall incidence of UTI due to ESBL strains was 12% in which the CCE of fosfomycin was significantly higher (p = 0.023).