Selective culture of Escherichia coli to prevent infective complications of transrectal ultrasound-guided prostate biopsy: Clinical efficacy and analysis of characteristics of quinolone-resistant Escherichia coli.

OBJECTIVES: To evaluate a regimen of targeted prophylaxis using rectal swab culture in patients undergoing transrectal ultrasound-guided prostate biopsy, and to investigate the characteristics of isolated fluoroquinolone-resistant Escherichia coli. METHODS: A prospective study was carried out from June 2013 through December 2014. Rectal swabs were cultured on agar plates containing either 2 µg/mL levofloxacin or 1 µg/mL sitafloxacin before transrectal ultrasound-guided prostate biopsy. Patients with susceptible organisms received levofloxacin or sitafloxacin, whereas those with resistant organisms received directed antimicrobial prophylaxis according to the results of the antimicrobial susceptibility test. Patients with infectious complications after prostate biopsy were identified, and characteristics of patients carrying fluoroquinolone-resistant Escherichia coli were analyzed. RESULTS: A total of 397 men underwent transrectal ultrasound-guided prostate biopsy. Of these patients, 74 (18.6%) had fluoroquinolone-resistant Escherichia coli. All fluoroquinolone-resistant Escherichia coli were susceptible to amikacin and meropenem. The risk factor for possible fluoroquinolone-resistant Escherichia coli was age of ≥73 years. Three (0.7%) patients who received appropriate antimicrobial prophylaxis had high-grade fever after the prostate biopsy. However, the pathogens were not fluoroquinolone-resistant Escherichia coli. CONCLUSIONS: Targeted antimicrobial prophylaxis in patients undergoing transrectal ultrasound-guided prostate biopsy can be associated with reducing severe infectious complications caused by fluoroquinolone-resistant Escherichia coli.

α1-blocker tamsulosin as initial treatment for patients with benign prostatic hyperplasia: 5-year outcome analysis of a prospective multicenter study.

OBJECTIVE: To comprehensively analyze the 5-year outcomes of tamsulosin treatment for patients with benign prostatic hyperplasia. METHODS: Tamsulosin (0.2 mg/day) was given to 112 patients who had International Prostate Symptom Scores ≥8. They were prospectively followed for 5 years with periodic evaluation. If tamsulosin had to be discontinued, the reason was determined. Treatment failure was considered in the case of disease progression (postvoid residual urine volume ≥200 mL, acute urinary retention, febrile urinary tract infection or hydronephrosis as a result of bladder outlet obstruction), conversion to other α1-blockers or need for surgery. An intention-to-treat analysis was carried out. RESULTS: A total of 34 patients (30.4%) continued the same medication for the overall study period, whereas 78 patients (69.6%) discontinued the medication. International Prostate Symptom Scores, Benign Prostatic Hyperplasia Problem Index and Quality of Life Index were significantly improved over the 5-year period. Treatment failure was observed in 21 patients (18.8%). Baseline prostate volume and postvoid residual urine volume were independent factors to predicting treatment failure. A total of 21 patients (18.8%) discontinued tamsulosin because of an improvement of symptoms. They were younger and had lower prostate-specific antigen levels than the remaining 91 patients. Their symptoms were stable even 1 year after termination of therapy. CONCLUSIONS: Long-term efficacy of tamsulosin was observed, although only a small portion of patients continued the treatment. α1-blocker monotherapy might be not appropriate for achieving a good long-term outcome in patients with a large prostate volume and a large amount of postvoid residual urine volume. Persistent improvement of symptoms, even after termination of tamsulosin, was observed in young patients with low prostate-specific antigen levels.

The nationwide study of bacterial pathogens associated with urinary tract infections conducted by the Japanese Society of Chemotherapy.

This study was conducted by the Japanese Society of Chemotherapy and is the first nationwide study on bacterial pathogens isolated from patients with urinary tract infections at 28 hospitals throughout Japan between January 2008 and June 2008. A total of 688 bacterial strains were isolated from adult patients with urinary tract infections. The strains investigated in this study are as follows: Enterococcus faecalis (n = 140), Escherichia coli (n = 255), Klebsiella pneumoniae (n = 93), Proteus mirabilis (n = 42), Serratia marcescens (n = 44), and Pseudomonas aeruginosa (n = 114). The minimum inhibitory concentrations of 39 antibacterial agents used for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. All Enterococcus faecalis strains were susceptible to ampicillin and vancomycin. Although a majority of the E. faecalis strains were susceptible to linezolid, 11 strains (7.8%) were found to be intermediately resistant. The proportions of fluoroquinolone-resistant Enterococcus faecalis, Escherichia coli, Proteus mirabilis, and S. marcescens strains were 35.7%, 29.3%, 18.3%, and 15.2%, respectively. The proportions of E. coli, P. mirabilis, K. pneumoniae, and S. marcescens strains producing extended-spectrum ß-lactamase were 5.1%, 11.9%, 0%, and 0%, respectively. The proportions of Pseudomonas aeruginosa strains resistant to carbapenems, aminoglycosides, and fluoroquinolones were 9.2%, 4.4%, and 34.8%, respectively, and among them, 2 strains (1.8%) were found to be multidrug resistant. These data present important information for the proper treatment of urinary tract infections and will serve as a useful reference for periodic surveillance studies in the future.

Decrease in incidence of surgical site infections in contemporary series of patients with radical cystectomy.

We previously reported that the incidence of surgical site infection (SSI) after radical cystectomy was 33% between January 1996 and December 2003 at Sapporo Medical University Hospital. Base on that result, we modified perioperative management for surgical wounds after January 2004. The modifications included the method of suturing and standardization of the period for removal of closed drains and surgical dressings. This study compared the incidence of SSI between the former and latter periods, and assessed risk factors for SSI. The study consisted of 109 patients between January 1996 and December 2003 (Group A), and 104 patients between January 2004 and December 2007 (Group B), who underwent radical cystectomy and urinary diversion or reconstruction. The incidence of SSI was reduced from 32.1% in Group A to 18.2% in Group B (p = 0.027). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from SSI wounds in 40.0% of patients in Group A and 42.1% of those in Group B. Preoperative MRSA bacteriuria was the only risk factor for SSI in both groups. The incidences of SSI in patients who had such bacteriuria were 45.4% in Group A and 50.0% in Group B. Modification of perioperative management for the surgical wound was partly responsible for the reduction of the incidence of SSI. In conclusion, MRSA is still the main isolated pathogen of SSI after radical cystectomy and this clinical problem remains a challenge to urologists. Effective countermeasures are needed for MRSA bacteriuria involved in the development of SSI.

Clinical relevance of single administration of prophylactic antimicrobial agents against febrile events after removal of ureteral stents for patients with urinary diversion or reconstruction.

OBJECTIVE: To assess the efficacy of antimicrobial prophylaxis when removing ureteral stents after urinary diversion or reconstruction and to establish the most appropriate prophylactic protocol to prevent febrile events. METHODS: We retrospectively investigated the incidence of febrile events in the two studies. Study 1 consisted of 39 patients who received antimicrobial prophylaxis and 31 who did not. Study 2 included 48 patients who were given oral fluoroquinolone (FQ) and 27 who had intramuscular injection of an aminoglycoside (AG). RESULTS: In study 1, the incidence of febrile events was significantly lower in patients receiving antimicrobial prophylaxis (26.0%) than in those not receiving it (51.6%) (P = 0.025, chi(2) test). In study 2 there was a 13% incidence of febrile events, which was much lower than the incidence found in study 1. The incidence of these events was similar between the two study groups, being 13% for those receiving FQ and 15% for those receiving AG. CONCLUSIONS: Prophylactic administration of antimicrobials reduces the incidence of febrile events after removal of ureteral stents. Both FQ and the AG are equally effective in this setting.

Efficacy of treatment with carbapenems and third-generation cephalosporins for patients with febrile complicated pyelonephritis.

The purpose of this study was to clarify the clinical relevance of carbapenem and third-generation cephalosporin treatment for febrile complicated pyelonephritis, which often leads to urosepsis. Parenteral antimicrobial treatment with a carbapenem or third-generation cephalosporin was administered to febrile patients and the treatment was switched to oral antimicrobial agents after they became afebrile. In principle, the duration of the course of antimicrobial chemotherapy was limited to a total of 14 days. Clinically, the success rates were 97.3% in the carbapenem group and 96.0% in the third-generation cephalosporin group. For microbiological efficacy, the success rates were 89.2% in the carbapenem group and 92.0% in the third-generation cephalosporin group. There were no serious adverse events in the course of the study. The treatment regimen with a carbapenem or a third-generation cephalosporin was highly effective for patients with febrile complicated pyelonephritis and was well tolerated. Either of these regimens could become one of the standard treatments for patients with febrile complicated pyelonephritis.

Disinfection by antiseptics in management of postoperative surgical wounds in urologic operations.

The objective of this study was to confirm that frequent disinfection by antiseptics is unnecessary on surgical wounds of urologic operations. Patients who received urologic operations were divided into 3 groups that had the same surgical dressings but different frequencies of disinfection and different antiseptics used. Surgical wounds were evaluated clinically and bacteriologically for the period until removal of sutures. Of the 97 patients randomly recruited for the study, 3 developed surgical-site infection (SSI). There was no significant difference in the incidence of SSI among the 3 groups. Bacterial counts of surgical wounds increased over time after operation, to similar extents in the 3 groups. The major isolate was Staphylococcus epidermidis, one of the normal florae on the skin. This strain was found at almost equal frequencies in all groups. In conclusion, our study suggested that covering with the surgical dressing without frequent disinfection by antiseptics was effective for prevention of SSI. Thus, traditional frequent disinfection should be abandoned.

[Questionnaire survey on the theory of antimicrobial prophylaxis in urologic surgery].

In order to establish an acceptable guideline for prevention of perioperative infection following urologic surgery, a questionnaire survey on the theory of antimicrobial prophylaxis (AMP) was conducted among urologists in Japan in February 2004. A reply was obtained from 149 urologists working for institutes located all over Japan from Hokkaido to Kyushu areas. Ninety-two percent of the urologists agreed that AMP should be administered 30 min before an incision, and 44% replied that an additional dose of AMP is required in the case of prolonged intervention. Penicillins or the 1st or 2nd generation cephems were used by 89 to 93% of the urologists in operations not including bowel segments, while 78% preferred such AMP agents in the procedures including bowel segments. AMP was terminated within 3 days in 87% for genital operations, in 70 to 76% for laparoscopic operations, in 54 to 65% for other clean or clean-contaminated operations, and in 24% for operations without the bowel segments. Especially, 58% of the urologists continued AMP for more than 5 days after operations with urinary diversion using the intestine. When compared with the previous questionnaire survey by Shinagawa et al, our survey demonstrated that standard consensus of AMP has spread widely among urologists in Japan, although the recommendations published in Europe and United States are still controversial in Japan. Thus, further well-designed clinical trials are required to establish original guidelines in Japan.

Does Baseline Prostate Volume Affect the Short-Term Outcome of Tamsulosin?

OBJECTIVE: To investigate the short-term efficacy of tamsulosin treatment for patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) according to baseline prostate volume (PV). METHODS: Tamsulosin, 0.2 mg/day, was prospectively given to 112 patients aged 50 years or older who had International Prostate Symptom Scores (IPSS) ≥ 8. The short-term efficacy was analyzed using the IPSS, quality of life (QOL) index, BPH problem index (BPI), maximum flow rate (Qmax ) and postvoid residual urine volume (PVR) at 4 weeks and 3 months after treatment considering the estimated PV at baseline. RESULTS: Of the 112 patients, 81 and 31 had PV of < 35 and ≥ 35 mL, respectively. The IPSS was significantly improved in patients with PV of < 35 mL (17.8 ± 5.9 at baseline, 13.5 ± 7.0 at 4 weeks, 11.9 ± 6.1 at 3 months) and in those with PV of ≥ 35 mL (17.4 ± 6.7 at baseline, 13.1 ± 7.0 at 4 weeks, 13.4 ± 6.2 at 3 months). There was no significant difference in the changes of the IPSS between the groups in a combined analysis model (P = 0.559). In addition, the model revealed no significant differences in changes in the QOL index, BPI, Qmax and PVR. CONCLUSION: The short-term efficacy of tamsulosin is observed irrespective of baseline PV. Thus, α1-blocker monotherapy should be considered for all patients with BPH/LUTS to rapidly relieve symptoms, although the long-term outcome is not promising for patients with a large PV at baseline.

Pharyngeal Neisseria gonorrhoeae detection in oral-throat wash specimens of male patients with urethritis.

Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in the pharynx has been highlighted in the prevention of the unexpected spread of sexually transmitted diseases. We tried to clarify the detection rate of Neisseria gonorrhoeae in the pharynx and the clinical relevance of oral-throat wash specimens to detect the organism in heterosexual men with gonococcal and nongonococcal urethritis. In our cohort of 79 male patients with urethritis, oral throat wash specimens were collected after they had gargled with normal saline for approximately 30 to 60 s. Positive pharyngeal N. gonorrhoeae was defined as a positive result on the strand displacement amplification test for the specimen from the oral-throat wash. N. gonorrhoeae was detected in the oral-throat wash specimens of 13 (31.7%) of the 41 male patients with gonococcal urethritis. Oral-throat wash with a nucleic acid amplification test can detect pharyngeal N. gonorrhoeae easily and efficiently.

Clinical efficacy of azithromycin for male nongonococcal urethritis.

The aim of this study was to confirm the clinical efficacy of a single-dose azithromycin (AZM) regimen (1000 mg) for patients with nongonococcal urethritis in real-life practice. The study finally evaluated 55 patients, 42 who were symptomatic and 13 who were asymptomatic, after excluding 40 who visited clinics only once. Sixteen of the symptomatic patients were diagnosed as having nongonococcal chlamydial urethritis, 7 as having nongonococcal nonchlamydial urethritis, and 19 as having urethritis without any microbial detection. Chlamydia trachomatis was detected in 11 asymptomatic patients, Mycoplasma genitalium in 1, and Ureaplasma urealyticum in 1. Of the patients who were microbiologically evaluated before and after single-dose AZM, microbiological cure was achieved in 87% (20/23) of those with symptomatic nongonococcal urethritis and in 100% (13/13) of those with asymptomatic nongonococcal urethritis. The clinical cure rate was 86% for the 42 symptomatic patients with detectable and undetectable pathogens. There were adverse events in 5 (9%) patients but they were commonly mild and self-limited. In conclusion, the single-dose AZM regimen was well tolerated and eradicated the estimated and potential pathogens of nongonococcal urethritis.

Gatifloxacin treatment for chronic prostatitis: a prospective multicenter clinical trial.

Antimicrobial treatment is usually used for chronic prostatitis. However, the efficacy of such treatment has not been fully evaluated. We conducted a study to evaluate the efficacy of gatifloxacin for patients with chronic prostatitis using the Japanese version of the National Institutes of Health Chronic Prostatitis Symptom Index (JPN-NIH CPSI). The study included 46 patients for final analysis. Patients who were younger than 65 years of age were treated with 200 mg gatifloxacin twice daily, and those who were 65 years and older were treated with 100 mg gatifloxacin twice daily, for 4-8 weeks. The study consisted of 10 patients in category II, 13 in category IIIA, 11 in category IIIB, and 12 who were unclassified. The gatifloxacin treatment resulted in significant reductions in the scores on the JPN-NIH CPSI. Of the total number of patients, 58.1% and 27.9% were 25% and 50% responders, respectively, 4 weeks after treatment, and these figures improved to 66.7% and 33.3%, respectively, 8 weeks after treatment. No significant difference was found in the changes in symptom scores between Category II and Category IIIA/IIIB groups. In conclusion, gatifloxacin treatment improved the symptoms in patients with chronic bacterial and nonbacterial prostatitis. This study is the first in this country to evaluate the efficacy of antimicrobial treatment for chronic prostatitis by using the NIH CPSI.

Comparison of 1-day, 2-day, and 3-day administration of antimicrobial prophylaxis in radical prostatectomy.

An adequate protocol for antimicrobial prophylaxis (AMP) in radical prostatectomy has not been established. We retrospectively compared the incidence and severity of infectious complications after radical prostatectomy with three different protocols for AMP. The study cohort consisted of 67 patients with prostate cancer who underwent radical prostatectomy at Hakodate Goryoukaku Hospital between January 2003 and December 2005. As a prophylactic antimicrobial agent, one of the cephalosporins or penicillins was administered intravenously to all patients. The analyzed protocols were for: (1) a 3-day group: administration of AMP until the second postoperative day (POD 2), (2) a 2-day group: administration of AMP until POD 1, and (3) a 1-day group: administration of AMP only on the operative day. The incidence and severity of infectious complications were retrospectively investigated. Three patients in the 3-day group (9.4%), 2 patients in the 2-day group (12.5%), and 2 patients in the 1-day group (10.5%) developed some infectious complications. The incidence of infectious complications was not significantly different among the three groups. No patients developed severe infectious complications such as sepsis. We conclude that single-day AMP is sufficient in patients with radical prostatectomy.

The 6-fluoro-8-methoxy quinolone gatifloxacin down-regulates interleukin-8 production in prostate cell line PC-3.

Fluoroquinolones exhibit immunomodulatory effects on monocytes and macrophages, in addition to their bactericidal activities. It remains unknown even whether the quinolones act directly on the prostate. This study was based on the understanding of the molecular mechanisms of the actions of the fluoroquinolones that can be used for the treatment of chronic prostatitis/chronic pelvic pain syndrome. We investigated whether the 6-fluroro-8-methoxy quinolone gatifloxacin (GFLX) affected the production and secretion of interleukin-8 (IL-8) in the prostate cell line PC-3. GFLX decreased the level of IL-8 release from unstimulated PC-3 cells. GFLX also attenuated IL-8 secretion from PC-3 cells stimulated with peptidoglycan, Mycoplasma hominis, phorbol ester, and tumor necrosis factor alpha (TNF-alpha), indicating that GFLX exhibits an anti-inflammatory effect on the prostate cell line. However, GFLX failed to alter activation of the NF-kappaB and AP-1 elicited by these stimulants. GFLX significantly attenuated the expression of IL-8 mRNA in TNF-alpha-stimulated PC-3 cells and down-regulated the transcriptional activity of the 5'-flanking region of the IL-8 gene from -1481 to +44 bp. The deletion construct without the 5'-flanking region from -1481 to -170 bp but not the construct without the region from -1481 to -188 bp reversed the suppressive effect of GFLX on IL-8 promoter activity. These results demonstrate that GFLX suppresses IL-8 expression in the prostate cell line by decreasing the promoter activity of the IL-8 gene.

Current survey of urinary tuberculosis in Hokkaido, Japan.

Urinary tuberculosis has been rare in recent years and its diagnosis is difficult because there are no disease-specific symptoms. We tried to clarify the occurrence of urinary tuberculosis in recent years in our area. During the past 5 years, there were 12 patients with urinary tuberculosis in the clinics that participated in this study. Their chief complaints were frequent voiding in 7 patients and gross hematuria in 3 patients. They were diagnosed by nucleic acid amplification tests and imaging modalities such as excretory urography, computed tomography, and/or cystoscopy. Most of the patients received multidrug treatment and had relatively favorable treatment outcomes. There has been a small but neglected number of patients with urinary tuberculosis in recent years. We should keep this rare and difficult-to-diagnose disease in mind and suspect it when patients complain of longstanding urinary symptoms with no obvious cause.

Detection of Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum DNAs in urine from asymptomatic healthy young Japanese men.

The aim of this study was to estimate the detection rates of Mycoplasma and Ureaplasma, which are presumptive causes of sexually transmitted diseases (STDs), in young men in Sapporo, Japan. In addition, we examined the associations among Chlamydia trachomatis, Mycoplasma, and Ureaplasma. A survey of 100 asymptomatic healthy male volunteers was carried out. C. trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum in first-voided urine specimens were detected by polymerase chain reaction assay. Detection rates were 1% for M. genitalium, 4% for M. hominis, 12% for U. urealyticum, and 23% for U. parvum. C. trachomatis was detected in 6% of samples. No M. hominis, U. urealyticum, or U. parvum was detected simultaneously in any sample positive for C. trachomatis. The detection rate of urinary M. genitalium was extremely low, which is similar to previous reports from Japan. The detection rates of urethral U. urealyticum and U. parvum were significantly related to sexual activity. We need to determine whether these pathogens have a role in the sexual transmission of disease or just in colonization.

Analysis of clinical manifestations of male patients with urethritis.

Almost all physicians involved in treating sexually transmitted infections recognize the specific clinical manifestations of patients with urethritis. However, in previous studies, the diagnosis of gonococcal urethritis was based on cultures or staining methods. In this study, we examined in detail the clinical manifestations of patients with urethritis diagnosed by the nucleic acid amplification test (NAAT). A total of 154 patients with male urethritis were included in the study. The NAAT could distinguish 64 patients with gonococcal urethritis, 45 patients with chlamydial urethritis, and 45 patients with nongonococcal and nonchlamydial urethritis. Forty-three (67.2%) patients with gonococcal urethritis had more severe symptoms, i.e., moderate or profuse urethral discharge, and cloudy or purulent discharge, than patients with chlamydial urethritis, nongonococcal and nonchlamydial urethritis. There were 39 (86.7%) patients in the chlamydial urethritis group with mild symptoms, clear discharge or none, and moderate or profuse discharge. Although the diagnosis of male urethritis can be performed by microbiological examination, the typical symptoms help us to distinguish each type of urethritis and understand this kind of disease.

Chlamydial seminal vesiculitis without symptomatic urethritis and epididymitis.

We previously reported that seminal vesiculitis was associated with acute epididymitis, and that Chlamydia trachomatis was the major causative pathogen for infection of the seminal vesicle, suggesting that seminal vesiculitis was a discrete disease entity. In this paper, we report two patients with bacteriologically and cytologically proven seminal vesiculitis who had asymptomatic urethritis but not epididymitis. The clinical courses of these patients suggest that chlamydial seminal vesiculitis may be a cause of asymptomatic infection of the urethra or subsequent development of acute epididymitis.

Prostate cell lines secrete IL-8 in response to Mycoplasma hominis through Toll-like receptor 2-mediated mechanism.

BACKGROUND: The roles of Toll-like receptor 2 (TLR2) and Mycoplasma in prostate inflammation remain unclear. We investigated whether Mycoplasma induced inflammatory cytokine secretion through TLR2-mediated mechanism in prostate cancer cell line. METHODS: Cell surface expression of TLR2 on PC-3 cells were examined by flowcytometry. PC-3 cells were stimulated with Mycoplasma hominis (M. hominis), and IL-8 secretion and NF-kappaB activation were examined. RESULTS: PC-3 cells expressed TLR2 mRNA and cell surface TLR2 protein. The membrane fraction of M. hominis induced IL-8 secretion from PC-3 cells and NF-kappaB activation in a concentration-dependent manner. Transient transfection of the dominant negative mutant TLR2(P681H) into PC-3 cells attenuated M. hominis-induced IL-8 secretion and NF-kappaB activation. Antibody against the extracellular TLR2 domain significantly suppressed M. homnis-induced IL-8 secretion from the prostate cell lines including PC-3, PrEC, and transformed myofibroblasts. CONCLUSIONS: These results clearly demonstrate that the prostate cell line can secrete inflammatory cytokine in response to M. hominis through a TLR2-mediated mechanism.

Clinical relevance of nucleic acid amplification test for patients with urinary tuberculosis during antituberculosis treatment.

The nucleic acid amplification test (NAAT) has been valuable in the diagnosis of urinary tuberculosis; however, no studies have attempted to determine the significance of NAAT post treatment. We encountered three patients with urinary tuberculosis who underwent sequential NAAT during antituberculosis chemotherapy and post treatment. All patients were diagnosed as having urinary tuberculosis by positive NAAT and specific renal deformity revealed by imaging. In two of the three patients, positive culture results were obtained and one was negative in standard culture. During antituberculosis chemotherapy, a negative NAAT was obtained from 3 to 5 months after the start of treatment and no positive culture results were obtained during the same period. At the end of chemotherapy, 6 months or more after the start of medication, all patients had negative NAAT results. These results suggest that NAAT for Mycobacterium tuberculosis provides an effective and rapid detection method for urinary tuberculosis both pre- and post-treatment.