Background: Antibiotic prophylaxis choice for transrectal prostate biopsy (TRPB) has been affected by the emergence of fluoroquinolone-resistant Escherichia coli (FQRE). Prebiopsy FQRE screening and targeted antibiotic prophylaxis may reduce post-TRPB bloodstream infection (BSI). We assessed the impact of a FQRE screening program on post-TRPB BSIs at an academic medical center. Methods: We implemented a FQRE screening program and targeted TRPB antimicrobial prophylaxis guidelines on May 1, 2017 (Fig. 1). We performed a retrospective cohort study of all TRPB and compared the incidence of post-TRPB BSI (within 7 calendar days) per 100 procedures before the intervention (January, 1, 2016, to April 30, 2017) and to the incidence after the intervention (May 1, 2017, to August 31, 2019). We used a subanalysis to compare BSI incidence between patients with positive (+) and negative () FQRE screens and appropriate prophylaxis use, defined as administration of guideline-recommended antibiotics. The Fisher exact test of independence was used to analyze nominal data. Results: The analysis included 2,157 TRPB procedures: 647 in the preintervention period and 1,510 in the postintervention period. FQRE screening compliance was 61% (n = 914) in the postintervention group (Fig. 2); 168 FQRE screens (18%) were positive. The median time from FQRE screen to procedure was 40 days (IQR, 13–69). Postprocedure BSI rates were higher in than those in the preimplementation group; however, this difference was not statistically significant (0.86 vs 0.46; OR, 2.01; P = .42). Among FQRE-screened patients, BSI rates differed significantly between FQRE+ and FQRE patients (2.98 vs 0.54; OR, 5.67; 95% CI, 1.21–28.94; P = .01). Screened patients receiving appropriate prophylaxis had lower BSI rates than those receiving inappropriate prophylaxis; however, this was not statistically significant (1.10 vs 2.02; OR, 0.54; P = .35). The most common BSI pathogen was E. coli (2 (67%) before implementation and 10 (77%) after implementation). Also, 5 E. coli BSIs (50%) were fluoroquinolone resistant in the postimplementation group compared to 1 (33%) in the preimplementation group. Of 13 postimplementation BSIs, 6 occurred in patients who received aminoglycosides perioperatively; however, all 6 BSI pathogens were aminoglycoside sensitive. Conclusions: Compliance with our FQRE screening program and antimicrobial prophylaxis protocol was moderate. Although pre- and postimplementation differences in BSI rates were not statistically significant, the high failure rate among patients receiving aminoglycosides was concerning and led to a change in TRPB prophylaxis guidelines. Reasons for increased BSI risk among FQRE+ patients may include prophylaxis agent, dose, timing, or other confounding factors associated with drug-resistant pathogens. Facilities implementing FQRE screening protocols should evaluate the efficacy of their program and periodically review screening compliance, prophylaxis dosing and timing adherence, and impact on patient-level outcomes.Funding: NoneDisclosures: None