To determine the optimal antibiotic prophylaxis strategy for transrectal prostate biopsy (TRPB) as a function of the local antibiotic resistance profile.

Directed or combination prophylaxis strategies were optimal for a wide range of resistance levels. Facilities using single-agent antibiotic prophylaxis strategies before TRPB should re-evaluate their strategies unless extremely low levels of antimicrobial resistance are documented.

In the base case, single-agent prophylaxis strategies were dominated. Directed prophylaxis strategy was the optimal strategy at a willingness-to-pay threshold of $50,000/QALY gained. Relative to the directed prophylaxis strategy, the incremental cost-effectiveness ratio of the combination strategy was $123,333/QALY gained over the lifetime time horizon. In sensitivity analysis, single-agent prophylaxis strategies were preferred only at extreme levels of resistance.

We developed a decision-analytic model to assess the cost-effectiveness of four antibiotic prophylaxis strategies: ciprofloxacin alone, ceftriaxone alone, ciprofloxacin and ceftriaxone in combination, and directed prophylaxis selection based on susceptibility testing. We used a payer's perspective and estimated the health care costs and quality-adjusted life-years (QALYs) associated with each strategy for a cohort of 66-year-old men undergoing TRPB. Costs and benefits were discounted at 3% annually. Base-case resistance prevalence was 29% to ciprofloxacin and 7% to ceftriaxone, reflecting susceptibility patterns observed at the Minneapolis Veterans Affairs Health Care System. Resistance levels were varied in sensitivity analysis.