Decision algorithm for prostate biopsy and antibiotic prophylaxis. The flowchart outlines the recommended pathways following the confirmation of an indication for prostate biopsy. The preferred approach is transperineal biopsy (TPB), beginning with exclusion of urinary tract infection via urinalysis, culture, and assessment of risk factors, followed by perineal antisepsis using chlorhexidine or octenidine/phenoxyethanol. Based on patient risk stratification, either omission of antibiotics (low risk) or a single dose of cefuroxime, cefazolin, or ampicillin/sulbactam (30–60 min prior to biopsy) is advised. Alternatively, if TPB is not feasible, the transrectal route (TRB) may be considered, with rectal antisepsis using povidone-iodine and targeted, non-fluoroquinolone, resistance-adapted antibiotic prophylaxis. This algorithm emphasizes clinical decision-making aimed at minimizing infectious complications. Low-risk patients are defined as those with sterile urine, no diabetes mellitus, no immunosuppression, no indwelling catheter for longer than 14 days, and no recent urinary tract infection. High-risk patients are those with one or more of the above factors.