Feasibility of Performing Transperineal Prostate Biopsy Without Antibiotic Prophylaxis in Low-Risk Patients: A Double-Blind Randomized Controlled Trial

Background Infectious complications remain a major concern following prostate biopsy and traditionally necessitate routine antibiotic prophylaxis. With the increasing adoption of the transperineal approach, infection rates have substantially decreased, raising questions regarding the necessity of routine antibiotic use. This study evaluated the safety of performing transperineal prostate biopsy (TPB) without antibiotic prophylaxis among low-risk patients. Methods A randomized, double-blind, parallel-group controlled trial was conducted at two tertiary centers in the Philippines. Low-risk patients scheduled for TPB were randomized to either no antibiotic prophylaxis (Group A) or a single intravenous dose of cefoxitin (Group B). TPBs were performed using MRI/ultrasound fusion-guided techniques. Primary outcomes were symptomatic urinary tract infection (UTI) and sepsis within 30 days after biopsy. Secondary outcomes included hospital admissions and non-infectious complications. Results A total of 140 participants were enrolled, with 70 patients assigned to each group. Baseline characteristics were comparable between groups. No symptomatic UTI or sepsis occurred in either group (0/70 vs. 0/70). The observed absolute difference was 0% (90% CI, −4.19 to 4.19). Although the observed confidence interval lay within the prespecified non-inferiority margin, the absence of events precluded definitive demonstration of non-inferiority. Positive urine cultures findings in asymptomatic participants were observed in 4.5% and 6.3% of participants in Groups A and B, respectively, none of which required treatment or progressed to clinically significant infection. No hospital readmissions occurred in either group. Urinary retention occurred in 2.9% and 4.3% of participants in Groups A and B, respectively. Conclusion Among carefully selected low-risk patients undergoing TPB, no symptomatic infections were observed regardless of antibiotic use. These findings suggest the feasibility of performing TPB without routine antibiotic prophylaxis while reducing unnecessary antibiotic exposure and supporting antimicrobial stewardship. However, larger adequately powered multicenter studies are needed before definitive conclusions regarding non-inferiority can be made. Trial Registration ISRCTN17045111. Retrospectively registered on June 8, 2025.