Ciprofloxacin Versus Fosfomycin for Empirical Prophylaxis Before Transrectal Prostate Biopsy: Clinical, Microbiological, and Patient-Reported Outcomes from a Prospective Study.

Background Transrectal ultrasound-guided prostate biopsy remains the gold standard in diagnosing prostate cancer, but is associated with infectious and non-infectious complications. Increasing fluoroquinolone resistance and regulatory restrictions have prompted evaluation of alternative prophylactic strategies, including fluoroquinolone-sparing agents and targeted prophylaxis. This study compared ciprofloxacin and fosfomycin as empirical prophylactic agents, focusing on microbiological concordance, clinical outcomes, and patient-reported outcomes. Methods In this prospective observational study, 265 men undergoing transrectal ultrasound-guided prostate biopsy received empirical antibiotic prophylaxis with either ciprofloxacin ( = 146) or fosfomycin trometamol ( = 119). Rectal swabs were obtained prior to biopsy, and antimicrobial susceptibility was analyzed post hoc. Infectious and non-infectious complications were recorded. Lower urinary tract symptoms (IPSS), erectile function (IIEF-5), and patient-reported quality of life were assessed before and after biopsy. Results Microbiological concordance between administered prophylaxis and rectal flora susceptibility was higher in the ciprofloxacin group than in the fosfomycin group (80.1% vs. 65.0%, = 0.007), while resistance rates were similar (10.9% vs. 10.2%). Post-biopsy fever occurred in 5.3% of patients, and hospitalization was required in 3.1%, with no significant differences between prophylaxis groups. IPSS increased significantly after biopsy ( < 0.001), while IIEF-5 scores remained unchanged. Patients with microbiological concordance reported significantly better post-biopsy quality of life ( = 0.006). Conclusions Ciprofloxacin and fosfomycin showed similar safety profiles as empirical prophylaxis before transrectal prostate biopsy. Although ciprofloxacin achieved higher microbiological concordance, fosfomycin remains a viable alternative. The link between microbial concordance and improved patient-reported quality of life underscores the importance of targeted prophylaxis and supports antimicrobial stewardship in prostate cancer diagnostics.