Penetration of piperacillin-tazobactam into human prostate tissue and dosing considerations for prostatitis based on site-specific pharmacokinetics and pharmacodynamics

This study aimed to investigate the penetration of PIPC-TAZ into human prostate, and to assess effectiveness of PIPC-TAZ against prostatitis by evaluating site-specific PK-PD. Patients with prostatic hypertrophy (n=47) prophylactically received a 0.5h infusion of PIPC-TAZ (8:1.2-0.25g or 4-0.5g) before transurethral resection of the prostate. PIPC-TAZ concentrations in plasma (0.5-5h) and prostate tissue (0.5-1.5h) were analyzed with a three-compartment PK model. The estimated model parameters were, then used to estimate the drug exposure time above the minimum inhibitory concentration for bacteria (T>MIC, the PD indicator for antibacterial effects) in prostate tissue for six PIPC-TAZ regimens (2.25 or 4.5g; once, twice, three times or four times daily; 0.5h infusions). Prostate tissue/plasma ratio of PIPC was about 36% both for the maximum drug concentration (C_max) and the area under the drug concentration-time curve (AUC). Against MIC distributions for isolates of Escherichia coli, Klebsiella species and Proteus species, regimens of 4.5g twice daily and 2.25g three times daily achieved a >90% probability of attaining the bacteriostatic target for PIPC (30% T>MIC) in prostate tissue; regimens of 4.5g three times daily and 2.25g four times daily achieved a >90% probability of attaining the bactericidal target for PIPC (50% T>MIC) in prostate tissue. However, against Pseudomonas aeruginosa isolates, none of the tested regimens achieved a >90% probability. PIPC-TAZ is appropriate for the treatment of prostatitis from the site-specific PK-PD perspective.