Clinical pharmacokinetics and pharmacodynamic target attainment of pazufloxacin in prostate tissue: Dosing considerations for prostatitis.

The present study examined the clinical pharmacokinetics of pazufloxacin in prostate tissue and estimated the probability of target attainment for tissue-specific pharmacodynamic goals related to treating prostatitis using various intravenous dosing regimens. Patients with prostatic hypertrophy received prophylactic infusions of pazufloxacin (500 mg, n = 23; 1000 mg, n = 25) for 0.5 h prior to transurethral prostate resection. Drug concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) were measured by high-performance liquid chromatography and used for subsequent noncompartmental and three-compartmental analysis. Monte Carlo simulation was performed to evaluate the probability of target attainment of a specific minimum inhibitory concentration (MIC) in prostate tissue: the proportion that achieved both area under the drug concentration over time curve (AUC)/MIC = 100 and maximum concentration (Cmax)/MIC = 8. Prostatic penetration of pazufloxacin was good with mean Cmax ratios (prostate tissue/plasma) of 0.82-0.99 and for AUC, 0.80-0.98. The probability of reaching target MIC concentrations in prostate tissue was more than 90% for dosing schedules of 0.25 mg/L for 500 mg every 24 h (500 mg daily), 0.5 mg/L for 500 mg every 12 h (1000 mg daily), 1 mg/L for 1000 mg every 24 h (1000 mg daily), and 2 mg/L for 1000 mg every 12 h (2000 mg daily). Importantly, the 2000 mg daily regimen of pazufloxacin produced a profile sufficient to have an antibacterial effect in prostate tissue against clinical isolates of Escherichia coli and Klebsiella pneumonia with MIC values less than 2 mg/L.

Risk assessment and usefulness of musculocutaneous flap transposition for recurrent septic arthritis of the hip in adults.

PURPOSE: Septic arthritis of the hip joint in adults often progresses to recurrent infections that require repeated surgeries for treatment. The purpose of the present study was to assess the risk of a recalcitrant hip infection and the usefulness of musculocutaneous flap transposition. METHODS: 15 adult patients who underwent surgeries for the treatment of hip infections were retrospectively analysed. Patients who recovered from infection by undergoing arthroscopy, open irrigation, debridement, continuous irrigation, resection arthroplasty, and/or the placement of antibiotic-loaded acrylic cement were classified into Group A (n = 10). Patients who showed residual infection after multiple surgeries and ultimately recovered after undergoing musculocutaneous flap transposition were classified into Group B (n = 5). The age at onset, sex, incidence of multi-drug-resistant organisms, incidence of infection at other sites, compromising factors, peak preoperative C-reactive protein level, and period from onset to initial surgery were compared between groups. RESULTS: There was a statistically significant difference in the period from onset to initial surgery (p = 0.024). The infections remained chronic after multiple surgeries in most patients who had complications and/or a poor general or local condition. All of the patients recovered after musculocutaneous flap transposition without the need for additional surgery and did not experience recurrence during the follow-up period in Group B. CONCLUSIONS: Delayed diagnosis and/or treatment and compromised host caused recurrent septic arthritis of the hip in adults. Musculocutaneous flap transposition may be a useful method for the treatment of recalcitrant hip infection.

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 0.5 h infusion of PIPC-TAZ (8:1.2-0.25 g or 4-0.5 g) before transurethral resection of the prostate. PIPC-TAZ concentrations in plasma (0.5-5 h) and prostate tissue (0.5-1.5 h) 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 4.5 g; once, twice, three times or four times daily; 0.5 h infusions). Prostate tissue/plasma ratio of PIPC was about 36% both for the maximum drug concentration (Cmax) 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 4.5 g twice daily and 2.25 g three times daily achieved a >90% probability of attaining the bacteriostatic target for PIPC (30% T > MIC) in prostate tissue; regimens of 4.5 g three times daily and 2.25 g 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.