ObjectivesTo compare the incidence of infectious complications after single-dose fosfomycin vs. standard fluoroquinolone (FQ)-based prophylaxis in patients undergoing transrectal ultrasound-guided biopsy of the prostate (TRUSBx), as there is an alarming trend worldwide of increasing resistance to FQs limiting their suitability as appropriate prophylaxis for TRUSBx.Patients and methodsA prospective study was conducted in 412 consecutive patients undergoing TRUSBx between February 2012 and June 2015. Patients were randomly divided into two groups; Group 1 (202 patients) who received single-dose fosfomycin (3 g, orally) 1–2 h before TRUSBx and Group 2 (210 patients) who received routine empirical prophylaxis in the form of oral ciprofloxacin 500 mg and metronidazole 500 mg at least 1 h before TRUSBx and continued this twice daily for 3 days before TRUSBx. We recorded all febrile and afebrile urinary tract infections (UTIs) within the 4 weeks after the procedure.ResultsThere was no difference in baseline demographics between the two groups. Total infectious complications occurred in four (1.9%) and 18 (8.5%) patients in Groups 1 and 2, respectively, which was statistically significant (P = 0.001). Escherichia coli was the most common isolated pathogen from urine cultures in all patients with infectious complications (68%). The other isolated bacterium, Klebsiella pneumoniae, was detected in four patients (18%). Urine cultures revealed FQ-resistant strains (73%), all of which were extended-spectrum β-lactamase-producing E. coli and K. pneumoniae.ConclusionsSingle-dose fosfomycin before TRUSBx significantly reduces infectious complications when compared with standard therapy. Fosfomycin is an effective agent for antimicrobial prophylaxis in patients undergoing TRUSBx, particularly in populations where FQ resistance is common.