Objective: It has been shown that antibiotic prophylaxis before transrectal ultrasound prostate biopsy (TRUS-Bx) reduces the incidence of post-biopsy infectious complications. Without the superiority of a particular antibiotic regimen, there are differences in the antibiotic regimens used by clinics. However, recently, there have been serious concerns about TRUS-Bx-related infectious complications due to the increase in fluoroquinolone (FQ)-resistant bacterial strains. To overcome this global problem, alternative antibiotic prophylaxis should be investigated and appropriate antibiotic management should be applied in patients who will undergo TRUS-Bx. This study aimed to determine the antibiotic susceptibility of the rectal flora based on rectal cultures before TRUS-Bx, to systematically determine the basic prevalence of FQ resistance, to investigate the relationship between FQ resistance and the risk of infection after TRUS-Bx, and to determine the susceptibility of Fosfomycin and trimethoprim-sulfamethoxazole (TMP-SMX) as an alternative to the FQ group. Materials and Methods: Rectal swab cultures were taken from each patient to undergo TRUS-Bx two days before the procedure. Two daily doses of 500 mg ciprofloxacin were given orally for one week, starting one hour before the procedure. All patients underwent 12 core biopsies. Results: Antibiograms obtained from rectal swabs showed sensitivity to FQ in 78 patients (89.7%), to Fosfomycin in 85 patients (97.7%), to TMP-SMX in 78 patients (89.7%). Conclusion: Although different antibiotic prophylaxis methods are discussed due to FQ resistance in today’s medical practices, FQ sensitivity continues at a high rate of 89.7% in our region and still seems to be a viable prophylaxis method.