Koichi Monden

Japanese guidelines for prevention of perioperative infections in urological field

Abstract:  For urologists, it is very important to master surgical indications and surgical techniques. On the other hand, the knowledge of the prevention of perioperative infections and the improvement of surgical techniques should always be considered. Although the prevention of perioperative infections in each surgical field is a very important issue, the evidence and the number of guidelines are limited. Among them, the preparation of guidelines has progressed, especially in gastrointestinal surgery. The Center for Disease Control and Prevention (CDC) proposed guidelines for the prevention of surgical site infections, which have been used worldwide. In urology, the original guidelines were different from those of general surgery, due to many endourological procedures and urine exposure in the surgical field. The Japanese Society of UTI Cooperative Study Group has thus framed these guidelines supported by The Japanese Urological Association. The guidelines consist of the following nine techniques: open surgeries, laparoscopic surgeries, transurethral resection of bladder tumor, ureterorenoscope and transurethral lithotripsy, transurethral resection of the prostate, prostate biopsy, cystourethroscope, pediatric surgeries in the urological field, and extracorporeal shock wave lithotripsy and febrile neutropenia. These are the first guidelines for the prevention of perioperative infections in the urological field in Japan. Although most of these guidelines were made using reliable evidence, there are parts without enough evidence. Therefore, if new reliable data is reported, it will be necessary for these guidelines to be revised in the future.

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)

Genetic Profiles of Fluoroquinolone-Resistant Escherichia coli Isolates Obtained from Patients with Cystitis: Phylogeny, Virulence Factors, PAIusp Subtypes, and Mutation Patterns

The low virulence of quinolone- and fluoroquinolone-resistant Escherichia coli strains is known, although the reasons for this remain unclear. We surveyed the mutation patterns of quinolone resistance determining regions (QRDRs), phylogenetic distribution, prevalence of 18 urovirulence genes, and PAIusp subtypes in 89 fluoroquinolone-resistant E. coli (FQREC) isolates obtained from patients with cystitis and compared them with those of their fluoroquinolone-susceptible counterparts (FQSEC). Phylogenetic group B2 was significantly less prevalent in FQREC than in FQSEC (49% versus 78%; P = 0.0138), but it still dominated, followed by phylogroup D (35%), in FQREC. When the prevalences of virulence factor (VF) genes were compared between FQREC and FQSEC, sfa/foc, cnf1, hly, kpsMT, ompT, ibeA, usp, and iroN showed significantly lower prevalences in FQREC than in FQSEC (1.1% versus 24% [P < 0.0001], 0% versus 29% [P < 0.0001], 7.9% versus 33% [P < 0.0001], 74% versus 90% [P = 0.01], 71% versus 87% [P = 0.017], 5.6% versus 37% [P < 0.0001], 54% versus 82% [P < 0.0001], and 7.9% versus 32% [P = 0.0001], respectively), whereas aer, iha, and ETTT showed significantly higher prevalences in FQREC (85% versus 36% [P < 0.0001], 66% versus 29% [P < 0.0001], and 53% versus 16% [P < 0.0001], respectively). Furthermore, a similar difference in prevalences of uropathogenic VF genes was seen between FQREC and FQSEC in phylogroup B2. This indicated that the low virulence in FQREC was intimately correlated with a lesser distribution of VFs in phylogroup B2, which dominated in FQREC and FQSEC. It was interesting that the mutation pattern of Ser83Leu and Asp87Asn encoded in gyrA and Ser80Ile and Glu84Val encoded in parC was frequently found in FQREC isolates that belonged to phylogroup B2 and that most of these isolates showed PAIusp subtype 2a. PAIusp subtypes 1a, 1b, and 2b, which were frequently seen in FQSEC, were rarely found in FQREC. These results suggested that the acquisition of fluoroquinolone resistance, e.g., mutations in QRDRs, might be a specific event in limited strains, such as those that possess PAIusp subtype 2a in phylogroup B2.

Nationwide survey of antibacterial activity against clinical isolates from urinary tract infections in Japan (2008)

In this study, the causative bacteria and their sensitivity to various antimicrobial agents as well as risk factors for quinolone-resistant Escherichia coli were investigated in patients with acute uncomplicated cystitis or complicated cystitis by isolation and culture of bacteria from urine samples. In total, 1312 strains were isolated from 1009 patients with acute uncomplicated cystitis, including E. coli (63.3%), Enterococcus faecalis (12.8%) and Streptococcus agalactiae (4.6%). In addition, 994 strains were isolated from 725 patients with complicated cystitis, including E. coli (36.4%), E. faecalis (19.2%), Klebsiella pneumoniae (5.0%), S. agalactiae (4.7%) and Pseudomonas aeruginosa (4.5%). At least 90% of E. coli isolates from acute uncomplicated cystitis showed sensitivity to fluoroquinolones and cephems, whilst 70.4-88.4% of E. coli isolates from complicated cystitis were sensitive to fluoroquinolones and 85.4-89.5% were sensitive to cephems. Factors associated with quinolone-resistant E. coli included two or more episodes of cystitis within 1 year, failure of quinolone therapy, underlying urinary tract disease, prior quinolone treatment within 1 month and age ≥ 75 years. It is important to confirm the sensitivity of causative bacteria for optimal antimicrobial therapy, and empirical antimicrobial agents should be selected by considering patient characteristics and other factors.

Japanese guideline for clinical research of antimicrobial agents on urogenital infections: the first edition

In the 1970s, clinicians and researchers specializing in urinary tract infections (UTIs) established and published the first-ever Criteria for Clinical Evaluation of Drug Efficacy on UTI. There had so far been no uniform criteria for the evaluation of drug efficacy, and different criteria for determining drug efficacy had been used in the development of drugs, which had caused problems in determining drug efficacy and had made it impossible to compare efficacy between drugs. To resolve these challenges, the Criteria for Clinical Evaluation of Drug Efficacy on UTI were established on the basis of the results of a large number of studies. The late Dr. Masaaki Ohkoshi, the late Dr. Joji Ishigami, the late Dr. Tsuneo Nishiura, Dr. Toyohei Machida, Dr. Yoshiaki Kumamoto, Dr. Joichi Kumazawa, Dr. Yukimichi Kawada, Dr. Sadao Kamidono, and other senior physicians made efforts to create the world’s first Criteria for Clinical Evaluation of Drug Efficacy on UTI, which had contributed enormously to the development of antimicrobial agents for UTIs. In 1989, an International Symposium entitled ‘‘Clinical Evaluation of Drug Efficacy on UTI’’ was held in Tokyo and offered opportunities to get international recognition of the Criteria for Clinical Evaluation of Drug Efficacy on UTI. Thereafter, the International UTI Symposium was established and came to be held biennially in conjunction with the International Congress on Chemotherapy. The joint symposium has been held ten times to date. In Japan, the Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on UTI were created by the UTI study group. The Criteria, which were those of the revised 3rd edition, involved various urological infections, including prostatitis, epididymitis, and urethritis, in addition to UTIs. Meanwhile, Infectious Diseases Society of America (IDSA)/ Food and Drug Administration (FDA) guidelines and the Criteria for Clinical Evaluation of Drug Efficacy were established in theUnitedStates andEurope, respectively,which led to an increased need for international harmonization aswell as globalization of the development of antimicrobial agents. To move with the times and to allow compatibility between data accumulated in Japan and data fromother countries, the Study Group on Urology, the Committee of Clinical Evaluation Methods, and the Japanese Society of Chemotherapy discussed and created the 4th edition of Criteria for Evaluation of Clinical Efficacy of Antimicrobial Agents on UTI (tentative) and its supplement in 1996. However, further international harmonization was needed, as international drug development, extrapolation of clinical data from other countries, and bridging studies had been increasing. In bringing about international M. Yasuda S. Takahashi H. Kiyota K. Ishikawa A. Takahashi S. Yamamoto S. Arakawa K. Monden T. Muratani R. Hamasuna H. Hayami T. Matsumoto UTI Subcommittee of the Clinical Evaluation Guidelines Committee, Japan Society of Chemotherapy, Tokyo, Japan

Microbiological outcome of complicated urinary tract infections treated with levofloxacin: a pharmacokinetic/pharmacodynamic analysis.

The pharmacodynamic targets representing 90% probability thresholds for bacterial eradication were determined in patients with complicated urinary tract infections (UTIs) treated with 500mg of levofloxacin every 24h for 7-14 days. Of 241 pre-treatment strains from 156 patients, 21 strains persisted after treatment. In each patient, plasma concentrations of levofloxacin were simulated based on population pharmacokinetic parameters and patient-specific data. Minimum inhibitory concentrations (MICs) of levofloxacin for the pre-treatment strains determined in our previous study were used. The pharmacodynamic targets representing 90% probability thresholds for bacterial eradication were determined by logistic regression analyses. For all the isolates, Gram-negative bacilli, Gram-positive cocci, Escherichia coli and Enterococcus faecalis, the target values of the area under the concentration-time curve (AUC)/MIC were 14.65, 31.46, 4.85, 43.00 and 3.06, respectively, and the targets of the maximum plasma concentration (C(max))/MIC were 1.22, 2.74, 0.39, 3.61 and 0.25, respectively. Such thresholds of AUC/MIC and C(max)/MIC in complicated UTIs would be lower than those in infections of other sites. In particular, the C(max)/MIC thresholds for Gram-positive cocci and E. faecalis were <1. These findings suggested that, in addition to its plasma concentration, the high concentration of levofloxacin in the urine might play a role in eradicating bacteria.

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.

Endoscopic correction of vesicoureteral reflux by subureteric Teflon (polytetrafluoroethylene) injection: review of 6-year experience.

Background:

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.