Research-Specific Tasks: To assess the efficacy, pharmacokinetics and prostate tissue penetration of tebipenem in a murine model of bacterial prostate infection using E. coli as the infecting organism.

Specific Aim 1: Susceptibility characterization of study isolate (s) Major Task: Bacterial isolates for susceptibility characterization Subtask 1: Identify appropriate bacterial isolates from archived bacterial samples. Subtask 2: Revive identified samples and create samples for dispatch to external vendor performing MIC determination. Subtask 3: Evaluating MIC50/90 determination for tebipenem and comparator antibiotics ertapenem, ciprofloxacin or levofloxacin, trimethoprim-sulfamethoxazole, and a cephalosporin against a panel of E.coli isolates. Subtask 4: Preparation and submission of a progress report Milestone 1 Achieved: •susceptibility characterization of study isolate(s). Specific Aim 2: Pilot study to examine the efficacy of a high dose of high dose of TBP-PI-HBr in a model of bacterial prostatitis Subtask 1: Pilot study to examine the efficacy of a high dose of a representative fluoroquinolone (ciprofloxacin or levofloxacin) in comparison to a high dose of TBP-PI-HBr for a period of 5 days by measuring bacterial burden in ≥ 6 mice at days 1, 3 and 5 post-inoculation in comparison to untreated animals. Total mice = 60 (24 untreated mice sacrificed on days 0, 1, 3 and 5 and 36 treated mice sacrificed on days 1, 3 and 5). Plasma and tissue homogenate will be collected from the TBP-PI-HBr-treated animals at the terminal timepoint. Subtask 2: Analysis of pilot study data, preparation of progress report slides. Milestone 2 Achieved: Pilot study to examine the efficacy of a high dose of a representative fluoroquinolone (ciprofloxacin or levofloxacin) in comparison to a high dose of TBP-PI-HBr for a period of 5 days by measuring bacterial burden in ≥ 6 mice at days 1, 3 and 5 post-inoculation in comparison to untreated animals. Major Task 3: Dose-response efficacy study with TBP-PI-HBr Subtask 1: Dose-response efficacy study with TBP-PI-HBr dosed three times daily every 8 hours by oral gavage at 4 dose levels with ≥ 6 mice per group. Comparator antibiotics of interest are ertapenem and a representative fluoroquinolone (ciprofloxacin or levofloxacin) (treatment regimens to be determined). Duration of the study to be determined based on the outcome of study 1. Total mice = 42 (6 per group: 1 untreated group, 4 TBP-PI-HBr-treated groups, and 2 comparator-treated groups). Subtask 2: Pharmacokinetic analysis of TBP-PI-HBr-treated mice infected with the study isolate via endpoint plasma and homogenized prostate tissue sampling. One group of 20 mice will be treated with a single dose of TBP-PI-HBr and will be sacrificed in the first 8 hours post-dose dose with 4 mice per timepoint. Two additional groups of 8 mice each will be dosed with TBP-PI-HBr with terminal plasma and tissue sampling at 2 timepoints. Total number of mice in study 3 is 36 mice. Samples will be transferred to a contract research organization for quantification of tebipenem concentrations in plasma and tissue. Subtask 3: Analysis of data and preparation of progress report Milestone 3 Achieved: Establishing dose-response efficacy and pharmacokinetics of TBP-PI-HBr in a murine model of bacterial prostatitis. Major Task 4: Final report on TBP-PI-HBr study