Shinya Uehara

Pharmacokinetic–pharmacodynamic target attainment analysis of doripenem in infected patients

This study was a pharmacokinetic (PK)-pharmacodynamic (PD) target attainment analysis of doripenem. Drug concentration data in plasma (115 samples) and urine (61 samples) from 18 infected patients were concurrently analysed to develop a more accurate population PK model for doripenem. In the final PK model, creatinine clearance (CL(Cr)) was the most significant covariate: CL(r) (L/h)=0.137xCL(Cr); CL(nr) (L/h)=2.49; V(1) (L)=8.29; Q (L/h)=8.10; and V(2) (L)=9.37, where CL(r) and CL(nr) are the renal and non-renal clearances, V(1) and V(2) are the volumes of distribution of the central and peripheral compartments, and Q is the intercompartmental (central-peripheral) clearance. Based on the PK model, a Monte Carlo simulation predicted the probabilities of attaining the bactericidal exposure target (40% of the time above the minimum inhibitory concentration (MIC)) in plasma and defined the PK-PD breakpoints (the highest MIC values at which the target attainment probabilities were >or=90%). The breakpoint for 500 mg every 8h (q8h) (1-h infusion) with a CL(Cr) of 80 mL/min (1 microg/mL) corresponded to those for 250 mg q8h with a CL(Cr) of 40 mL/min and 250 mg every 12h with a CL(Cr) of 20 mL/min. Prolonging the infusion time was a more effective strategy than dose escalation to increase the breakpoint. These results provide guidance for constructing a PK-PD-based strategy for dosing guidance for tailoring doripenem regimens.

Nerve growth factor level in the prostatic fluid of patients with chronic prostatitis/chronic pelvic pain syndrome is correlated with symptom severity and response to treatment

Study Type – Therapy (case series)

Indications for Ureteropyeloscopy Based on Radiographic Findings and Urine Cytology in Detection of Upper Urinary Tract Carcinoma

OBJECTIVE To verify the indication of diagnostic ureteropyeloscopy based on clinical features for upper urinary tract urothelial cancer with over 100 patients and over a 10-year series. METHODS From January 1997 to December 2008, consecutive 129 units in 124 patients underwent ureteropyeloscopy to obtain a definitive diagnosis of upper urinary tract cancer or to rule out a malignancy. Patients were divided into four subgroups based on voided urine cytology and preoperative radiographic findings: group A (n = 8), positive urine cytology and positive radiographic findings; group B (n = 4), positive cytology and negative radiographic findings; group C (n = 55), negative cytology and positive radiographic findings and group D (n = 62), gross hematuria originating from the upper urinary tract with negative cytology and negative radiographic findings. Ureteropyeloscopic findings were compared with radiographic and cytological results. Adverse effects were also investigated. RESULTS In group A, all patients had confirmed cancer. In group B, one revealed small cancer and the remaining three confirmed carcinoma in situ by biopsy with ureteropyeloscopy. In groups C and D, 33 patients (60%) and four (6.5%) revealed cancer. Seventy-eight patients out of 80 (97.5%) in groups C and D were confirmed to have benign disease. No patient was found with malignancy during follow up after negative finding of ureteropyeloscopy. CONCLUSIONS Ureteropyeloscopy can help in detecting upper urinary tract cancer or to rule out malignancy for patients with negative voiding cytology. However, ureteropyeloscopy is redundant for patients with positive radiographic findings and positive voiding cytology.

Ureteroscopic management of chronic unilateral hematuria: a single-center experience over 22 years.

Objective To analyze the short and long term safety and efficacy of ureteroscopic evaluation and management of chronic unilateral hematuria. Methods We retrospectively reviewed patients with chronic unilateral hematuria from 1987 to 2008. The distal to middle ureter was evaluated with a semi-rigid ureteroscope without a guidewire. Subsequently, the flexible ureteroscope was advanced into the upper ureter to the renal pelvis using a low-pressure automated irrigant system (Uromat™). Lesions identified ureteroscopically were treated with diathermy fulguration. Results One hundred and four (56 male, 48 female) patients were identified, with a median age of 37 (14–80) years and median follow-up of 139 (34–277) months. The median preoperative duration of gross hematuria was 5 (1–144) months. Endoscopic findings included 61 (56%) minute venous rupture (MVR; a venous bleeding without clear abnormalities), 21 (20%) hemangioma (vascular tumor-like structure), 3 (3%) varix (tortuous vein), 1 (1%) calculus and 18 (17%) no lesions. The incidence of “no lesions” was less in the recent 12 years (9%) than the first 10 years (27%), while the incidence of MVR increased from 40 to 66% (p<0.05). All patients were treated endoscopically. Immediate success rate was 96% (100% in the recent 12 years). Long-term recurrent gross hematuria rate was 7%. Six resolved spontaneously and only 1 required ureteroscopy, revealing a different bleeding site. Conclusion Ureteroscopy and diathermy fulguration is highly useful for evaluation and treatment of chronic unilateral hematuria. Sophisticated technique and improved instrumentation contributes to a better outcome.

Should urologists care for the pharyngeal infection of Neisseria gonorrhoeae or Chlamydia trachomatis when we treat male urethritis

Detection of Neisseria gonorrhoeae (NG) or Chlamydia trachomatis (CT) from the pharynx of women or men is not uncommon. However, there is no recommendation how urologists should care for the pharyngeal infection of men with urethritis in Japan. The aim of this study is to clarify the prevalence of NG or CT infection in the pharynx of men and to show a recommendation for urologists. The Japanese reports about the detection of NG or CT from the pharynx or the oral cavity of men in Japan are reviewed in the literature from 1990 to 2011. The prevalence of NG or CT in the pharynx was 4% or 6% in men who attended clinics, and 20% or 6% in men who were positive for NG or CT from genital specimens, respectively. Single 1-g dose ceftriaxone was recommended to treat pharyngeal NG, but no evidence was found for pharyngeal CT. There was not enough evidence for recommendation. However, when men with urethritis only caused by NG or CT are treated through the guideline of the Japanese Society of Sexually Transmitted Infection, we do not think additional tests or treatment for the pharynx are needed when a single 1-g dose ceftriaxone for gonococcal urethritis or a single 1- or 2–g dose azithromycin is prescribed for chlamydial urethritis in Japan.

Detection and isolation of nanobacteria-like particles from urinary stones: long-withheld data.

Objectives:  To report our experimental results on detection and isolation of nanobacteria‐like particles (NLP) from urinary stone samples.

Treatment of acute uncomplicated cystitis with faropenem for 3 days versus 7 days: multicentre, randomized, open-label, controlled trial

OBJECTIVES The increasing prevalence of resistant bacteria such as fluoroquinolone-resistant or extended-spectrum β-lactamase-producing strains in pathogens causing acute uncomplicated cystitis has been of concern in Japan. Faropenem sodium is a penem antimicrobial that demonstrates a wide antimicrobial spectrum against both aerobic and anaerobic bacteria. It is stable against a number of β-lactamases. METHODS We compared 3 and 7 day administration regimens of faropenem in a multicentre, randomized, open-label, controlled study. RESULTS In total, 200 female patients with cystitis were enrolled and randomized into 3 day (N = 97) or 7 day (N = 103) treatment groups. At the first visit, 161 bacterial strains were isolated from 154 participants, and Escherichia coli accounted for 73.9% (119/161) of bacterial strains. At 5-9 days after the completion of treatment, 73 and 81 patients from the 3 day and 7 day groups, respectively, were evaluated by intention-to-treat analysis; the microbiological efficacies were 58.9% eradication (43/73), 20.5% persistence (15/73) and 8.2% replaced (6/73), and 66.7% eradication (54/81), 6.2% persistence (5/81) and 7.4% replaced (6/81), respectively (P = 0.048). The clinical efficacies were 76.7% (56/73) and 80.2% (65/81), respectively (P = 0.695). Adverse events due to faropenem were reported in 9.5% of participants (19/200), and the most common adverse event was diarrhoea. CONCLUSIONS The 7 day regimen showed a superior rate of microbiological response. E. coli strains were in general susceptible to faropenem, including fluoroquinolone- and cephalosporin-resistant strains.

Post-operative Infection by Pathogenic Micro-organisms in the Oral Cavity of Patients with Prostatic Carcinoma

The aim of this study was to analyse the change in the oral cavity microflora of 14 patients who had undergone a radical prostatectomy for prostatic carcinoma. The detection of microorganisms in the oral cavity was compared before and after the surgical procedure. Post-operative infection, defined as those patients who had increased Candida species counts and/or pathogenic bacteria only at the postoperative examination, was observed in 10 patients. Six patients showed increased Candida species counts at the post-operative examination compared with the pre-operative examination. In five patients, pathogenic bacterial species were detected at the post-operative examination but not at the pre-operative examination. One patient had detectable pathogenic bacterial species only at the post-operative examination along with increased Candida species counts. Our findings suggest that pre-operative oral hygiene to remove bacterial and Candida species from patients who are scheduled for surgical procedures is important for satisfactory clinical outcomes.

Biofilm and Urogenital Infections

Bacterial adherence and the growth of bacteria on solid surfaces as biofilm are both naturally occurring phenomena. Biofilms can be defined as an accumulation of microorganisms and their extracellular products forming structured communities attached to a surface. Biofilms are able to build up under natural circumstances, for instance on the urothelium or prostate stones and they can also colonize the surfaces of implanted medical devices. Biofilm infections have a major role on temporary and permanent implants or devices placed in the human body. In the process of endourological development a great variety of foreign bodies have been invented besides urethral catheters like ureter, prostatic stents, percutan nephrostomy, penile, testicular implants and artificial urinary sphincters. Many biofilms are quite harmful but others can have a positive impact, namely lining healthy intestine and female genito-urinary tract. Biofilms have significant implications for clinical pharmacology, particularly related to antibiotic resistance, drug adsorption onto and off of devices, and minimum inhibitory concentrations of drugs required for effective therapy.

Rhabdomyosarcoma discovered in the adrenal region of an elderly hypertensive patient

Rhabdomyosarcoma is rare soft-tissue tumor that is more prevalent among children. In contrast, rhabdomyosarcomas are extremely rare in adults, with soft-tissue sarcomas making up o1% of malignancies in adults and rhabdomyosarcomas accounting for o2% of all soft-tissue sarcomas.1 Rhabdomyosarcoma in the adrenal region has not been documented to date. We here report a very rare case of rhabdomyosarcoma occurred in the left adrenal region of an elderly hypertensive patient. A 76-year-old Japanese woman with a 5-year history of hypertension (occasionally systolic blood pressure 4200 mm Hg) was referred to our hospital. The patient had complained about left flank pain for 2 months. Abdominal computed tomography detected a left adrenal mass of 7 cm in diameter (10–40 Hounsfield units) heterogeneously contrasted at the early enhancement (Figure 1). The tumor exhibited a heterogeneous echo with regular surface by ultrasound. Magnetic resonance imaging exhibited a diffusely low-intensified adrenal mass by T1-weighted images. T2-hyperintensity was spottily detected in the central area (Figure 1). Fat-suppression magnetic resonance imaging showed the least inclusion of adipose tissue in the tumor. Scintigram with 131I-adosterol showed almost normal pattern of bilateral uptake in the adrenal regions. Peripheral blood cell count, liver and renal functions, blood glucose and electrolytes were normal. The basal endocrine data of adrenal functions were within normal ranges as follows: plasma adrenocorticotropin, 29.2 pg ml 1 (normal: 7–55); cortisol, 10.6mg dl 1 (8–25) with normal circadian fluctuation and significant suppression (o0.5mg dl 1) after 1 mg