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

Background<b>:</b> 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<b>:</b> In this prospective observational study, 265 men undergoing transrectal ultrasound-guided prostate biopsy received empirical antibiotic prophylaxis with either ciprofloxacin (<i>n</i> = 146) or fosfomycin trometamol (<i>n</i> = 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<b>:</b> 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%, <i>p</i> = 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 (<i>p</i> < 0.001), while IIEF-5 scores remained unchanged. Patients with microbiological concordance reported significantly better post-biopsy quality of life (<i>p</i> = 0.006). Conclusions<b>:</b> 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.