The clinical efficacy of garenoxacin for male non-gonococcal urethritis.

Sitafloxacin (STFX) is an alternative treatment against azithromycin-resistant Mycoplasma genitalium (MG), whereas STFX-resistant MG have appeared recently. Therefore, another antimicrobial regimen for non-chlamydial non-gonococcal urethritis (NGU) is required. Garenoxacin (GRNX) is a fluoroquinolone against respiratory infections, not against urethritis in Japan, but its in-vitro antimicrobial activity against MG is known as similar to or higher than that of moxifloxacin. To clarify the efficiency of GRNX against MG, we examined the clinical efficacy of GRNX for NGU. Seventy-nine male patients with NGU were enrolled and treated with GRNX once daily for 7 days. For assessing microbiological and clinical efficacies, the bacteria including Chlamydia trachomatis (CT), MG, Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and Ureaplasma parvum (UP) were detected by means of nucleic acid amplification tests before- and after-treatment. After excluded 3 patients, seventy-six patients were evaluated: the median age; 31 (20-61) years, vaginal infection (66%); the most common infectious route and commercial sex worker (43%); the most common source. There were 50 bacteria-positive NGU cases, including 10 multiple bacterial infections. Clinical cure rate was 85.7% (36/42). Detection frequency of each bacterium was similar to the previous reported. The eradication rates of CT, MG, MH, UU and UP were 96.1%, 71.4%, 100%, 85.7% and 100%, respectively. These results indicate that GRNX has the excellent efficacies for NGU except those of MG. Further study of drug-resistant MG urethritis; for instance, studies on the clinical effectiveness of long-term such as 2-week medication of GRNX or the efficacy of alternative treatment regimens are necessary.

[A Case of Bacteremia Urinary Tract Infection Caused by Stenotrophomonas maltophilia in an 8-month-old Boy].

Bacteremic urinary tract infection (UTI) caused by Stenotrophomonas maltophilia rarely occurs in pediatric patients. We report a case of bacteremic UTI caused by S. maltophilia in an 8-month-old boy with a congenital ureteropelvic junction obstruction on the left side. The patient was brought to our hospital with a chief complaint of fever. He had undergone a nephrostomy tube insertion 4 months previously, and the tube had been removed 2 weeks before presentation at our hospital. He had a white blood cell count of 6,100/µL and a serum C-reactive protein level of 4.51 mg/dL. A microscopic urinalysis and Gram stain showed numerous Gram-negative bacilli and many leukocytes, and an ultrasonography showed grade 4 hydronephrosis of the left kidney. Based on these findings, we diagnosed the infant as having a complex UTI and started the intravenous administration of piperacillin/tazobactam. After 2 days, a urine culture showed Gram-negative bacilli (107 CFU/mL). Gram-negative bacilli were also cultured from two blood samples that were taken from different vessels at the time of admission. The Gram-negative bacilli were identified as S. maltophilia via the automated bacterial identification system. The patient recovered after a 2-week intravenous piperacillin/tazobactam treatment and subsequent oral treatment with trimethoprim-sulfamethoxazole. Since medical devices are susceptible to contamination with S. maltophilia, we suspect that the nephrostomy tube was the most likely source of infection.

A CASE OF A CARCINOSARCOMA OF THE PROSTATE.

Carcinosarcoma of the prostate is a rare but aggressive tumor characterized by combination of malignant epithelial and mesenchymal cells. We encountered a case of carcinosarcoma of the prostate. A 78-year-old man with urinary retention was diagnosed with benign prostatic hyperplasia on the basis of the ultrasonography and rectal examination findings, negative result of prostate biopsy. Transurethral resection of the prostate was performed, and the pathological diagnosis was carcinosarcoma of the prostate with squamous cell carcinoma. The patient died of disease 5 months after the diagnosis of carcinosarcoma. A total of 17 cases of carcinosarcoma of the prostate including the present case, have been reported in the Japanese literature to date. Herein we review the 17 cases and discuss the clinical features.

Japanese nationwide surveillance in 2011 of antibacterial susceptibility patterns of clinical isolates from complicated urinary tract infection cases.

To investigate antimicrobial susceptibility patterns of various bacterial pathogens isolated from complicated urinary tract infection (UTI) cases, the Japanese Society of Chemotherapy, the Japanese Association of Infectious Disease, and the Japanese Society of Clinical Microbiology conducted the second nationwide surveillance from January to September 2011. With the cooperation of 42 medical institutions throughout Japan, 1036 strains belonging to 8 clinically relevant bacterial species were collected. Among methicillin-resistant Staphylococcus aureus (MRSA) strain, the vancomycin (VCM) MIC for 5.5% (3/55) of the strains was 2 µg/mL. Ampicillin, VCM, and linezolid were relatively active against 209 Enterococcus faecalis strains. The proportion of fluoroquinolone (FQ)-resistant strains was >20%. The MIC90 of FQs against the 382 Escherichia coli strains was 2-64 mg/L and the proportion resistant to FQs was approximately 30%. However, susceptibility of E. coli to sitafloxacin was still high (MIC90 = 2 mg/L). Fifty-eight (15.2%) of 382 E. coli, 6 (4.5%) of 132 Klebsiella pneumoniae, 1 (2.4%) of 41 Klebsiella oxytoca and 4 (6.8%) of 59 Proteus mirabilis strains were suspected of producing extended-spectrum beta-lactamase. Of 93 Pseudomonas aeruginosa strains, the proportions resistant to imipenem, amikacin, and ciprofloxacin were 21.5%, 4.3%, and 20.4%, respectively. Four strains (4.3%) were found to be multidrug-resistant. In complicated UTI cases, all of MRSA and E. faecalis were susceptible to all anti-MRSA agents. Sitafloxacin was active against other FQ-resistant E. coli strains. The isolation of extended-spectrum beta-lactamase-producing and multidrug-resistant strains increased.

Comparison of free and anonymous testing for HIV and sexually transmitted infections between the University Hospital and Health Center.

We gathered data regarding age, sex, and positivity rates for human immunodeficiency virus (HIV), syphilis, gonococcus, and chlamydia from individuals who underwent free and anonymous sexually transmitted infection (STI) testing conducted at the Jikei University School of Medicine Hospital (our hospital). These data were compared to results of subjects who underwent similar testing at the Minato Health Center and several private facilities of urologists and gynecologists belonging to the Minato Ward Medical Association. The positivity rate of chlamydia was found to be high in female subjects, particularly at the Minato Health Center, with 15 of 194 subjects (7.73 %) testing positive. In our hospital, we only detected 3 of 133 subjects (2.26 %) who were gonococcus positive. On the other hand, at the doctor's facilities, 10 of 188 male subjects (5.32 %) were syphilis positive, and 8 of 185 male subjects (4.32 %) were chlamydia positive, thus showing high positivity rates for both infections. At our hospital, 1 of 231 subjects was positive for gonococcus and 4 of 230 subjects (1.74 %) were positive for chlamydia, thus showing lower positivity rates for both infections. HIV-positive subjects were, however, only confirmed at our hospital, with 2 of 243 subjects (0.82 %) being positive. We were able to diagnose infected patients using free and anonymous STI testing at hospitals, and the same as at doctors' facilities. This result suggests that the hospitals that have many opportunities to diagnose HIV patients may become potential candidates for the development of new consultation facilities, establishment of testing facilities, and enhancement of consultation processes that include STI prevention.

[Efficacy and safety of levofloxacin to non-gonorrheal urethritis].

We investigated the efficacy and safety of levofloxacin (LVFX) 500mg once a day in patients with non-gonorrheal urethritis. Men, aged 20 years or older, with urethritis symptoms, and detection of Chlamydia trachomatis (C. trachomatis) or Mycoplasma genitalium (M. genitalium) by a microbiological examination were eligible for this study. Patients were administered LVFX 500mg, orally, once a day and the dosage period was seven days. We assumed 22 patients for a safety and efficacy analysis. In 22 patients, 17 patients had urethritis with C. trachomatis, 4 patients urethritis with M. genitalium, and one patient mixed infection of C. trachomatis and M. genitalium. In the clinial study, the primary endpoint was set as the bacteriological eradication rate at two to four weeks after completion of treatment. The bacterial eradication rate in the urethritis was 86.4% (19/22). The bacterial eradication rate in the urethritis with C. trachomatis, M. genitalium, and mixed infection of C. trachomatis and M. genitalium were 94.1% (16/17), 50.0% (2/4), 100% (1/1), respectively. A significant difference was not recognized among the three groups. The clinical efficacy at two to four weeks after completion of treatment was 90.9% (20/22). The clinical efficacy rates in the urethritis with C. trachomatis, M. genitalium, and mixed infection of C. trachomatis and M. genitalium were 100% (17/17), 50.0% (2/4), 100% (1/1), respectively. The efficacy rate of urethritis with M. genitalium was significantly low. No adverse drug reactions were observed. These results suggest that once-a-day levofloxacin (500mg) is effective and safe treatment for non-gonorrheal urethritis.

[Status and future of sexually transmitted diseases in Japan].

According to the results of the fixed-point survey, the incidence of both genital chlamydial infection and gonococcal infection has tended to decrease since 2003 in Japan. This trend has been more marked in young persons of both sexes. However, it has been suggested that the fixed-point survey has a problem with respect to the method of selecting designated medical institutions for notification. Moreover, it should be remembered that there are many patients without symptoms in addition to patients with symptomatic sexually transmitted diseases. We performed a group study of patients with asymptomatic sexually transmitted diseases over 3 years. As a result, it was confirmed that the prevalence of asymptomatic genital chlamydial infection was highest among female high school students aged 16-18 years, and was approximately 5% even among healthy men in their twenties. Based on these results, to prevent the spread of sexually transmitted diseases in the young, it seems necessary to perform large-scale screening for these diseases(especially in young persons) and establish a system that allows the results of screening to ensure early detection and treatment of sexually transmitted diseases.

Broad impact of extracellular DNA on biofilm formation by clinically isolated Methicillin-resistant and -sensitive strains of Staphylococcus aureus.

Staphylococcus aureus is a major causative agent for biofilm-associated infections. Inside biofilms, S. aureus cells are embedded in an extracellular matrix (ECM) composed of polysaccharide-intercellular adhesins (PIA), proteins, and/or extracellular DNA (eDNA). However, the importance of each component and the relationship among them in biofilms of diverse strains are largely unclear. Here, we characterised biofilms formed by 47 S. aureus clinical isolates. In most (42/47) of the strains, biofilm formation was augmented by glucose supplementation. Sodium chloride (NaCl)-triggered biofilm formation was more prevalent in methicillin-sensitive S. aureus (15/24) than in methicillin-resistant strain (1/23). DNase I most effectively inhibited and disrupted massive biofilms, and Proteinase K was also effective. Anti-biofilm effects of Dispersin B, which cleaves PIA, were restricted to PIA-dependent biofilms formed by specific strains and showed significant negative correlations with those of Proteinase K, suggesting independent roles of PIA and proteins in each biofilm. ECM profiling demonstrated that eDNA was present in all strains, although its level differed among strains and culture conditions. These results indicate that eDNA is the most common component in S. aureus biofilms, whereas PIA is important for a small number of isolates. Therefore, eDNA can be a primary target for developing eradication strategies against S. aureus biofilms.

[A case of acute bronchitis caused by Neisseria meningitidis associated with HIV infection].

We report the case of a patient with acute bronchitis caused by Neisseria meningitidis associated with HIV infection. A 36-year-old homosexual Japanese man being treated for HIV infection and reporting fever and a productive cough was found in laboratory findings to have elevated C-reactive protein but no leukocytosis. Chest radiography showed no infiltrates in either lung, but a sputum smear yielded large numbers of Gram-negative cocci, including some phagocytized by white blood cells. One day later N. meningitidis was reported to be the predominant isolate from sputum culture. The patient was diagnosed with acute bronchitis caused by N. meningitidis. The strain isolated from this patient was in serogroup B. The sequence type based on multilocus sequence typing was ST-5583, a subtype of ST-32. This strain is resistant to penicillin G in vitro, so we administered tosufloxacin at 600mg b.i.d., which showed excellent efficacy. Because of frequent sex with many men, homosexual contact was suspected as a possible route of infection. Meningococcal infections apart from meningitis rarely are surveyed epidemiologically in Japan, and the frequency of meningococcal infections in general is not clear. Vigilance is needed to identify trends in meningococcal infection, because N. meningitidis can cause acute bronchitis.

[A case of leptospirosis caused by Leptospira borgpetersenii serovar sejroe infected in Bali Island, Indonesia].

We report a patient with leptospirosis caused by Leptospira borgpetersenii serovar Sejroe infection on Bali Island, Indonesia. This 33-year-old Japanese man had stayed at a resort hotel on the island from July 8 to July 13 2004. At the hotel, he swam in the pool, walked barefoot, and lied down in the grass. He developed a high fever and headache 7 days after completing his trip, and was admitted to our hospital on July 23. On admission he showed conjunctival suffusion and complained of myalgias. Laboratory findings included granulocytosis and elevated CRP. Plasmodium spp. were not found in blood smears, and no pathogenic bacteria were isolated from blood or fecal cultures. We diagnosed the patient as leptospirosis upon detection of slender coiled organisms with characteristic morphology by darkfield examination of blood sample. Minocycline 100 mg i.v.b.i.d. showed excellent efficacy. A microscopic agglutination test (MAT) during the convalescent stage demonstrated a significant increase in antibodies against L. borgpetersenii serovar Sejroe, confirming the diagnosis of leptospirosis. Despite occurrence of a pandemic of leptospirosis in certain Southeast Asian countries including Indonesia, information concerning pandemic disease is limited. In addition serovars of "imported" cases representing infection in pandemic areas differ widely from those in domestic cases. Adequate laboratory support therefore is crucial for accurate diagnosis of leptospirosis.

[Primary, nonviral, hepatocellular carcinoma in patients with prostate cancer treated by hormone therapy: 2 case reports].

We studied two cases of primary, hepatocellular carcinoma (HCC) that occurred following hormone therapy (estrogen therapy in one case and total androgen blockade therapy in another) for stage D2 prostate cancer. Prostate cancer is considered to be hormone-dependent, and androgens appear to be important hormonal factors. However, hepatocellular carcinoma has been shown to have both estrogen and androgen receptors, suggesting that this may be dependent on estrogen or androgen. Reported here are two unique cases of hepatocellular carcinoma in patients with prostate cancer; the pathogenesis of HCC in these patients was suspected to be related to diethylstilbestrol (DES) therapy and antiandrogen therapy for their prostate cancer.

[Gnathostomiasis caused by Gnathostoma spinigerum etiologically diagnosed upon extraction of the worm from the skin].

We report a patient with gnathostomiasis in whom a specific diagnosis of Gnathostoma spinigerum infestation was made morphologically upon removal of the worm. A 47-Year-old Japanese male on a business trip to Vietnam ate fried frog with a Vietnamese friend in January 2002, the friend was diagnosed with gnathostomiasis in June 2002. The patient noted swelling of the right leg with migration to the right arm, prompting him to our hospital in February 2003. Hematologic examination showed eosinophilia, and specific anti-gnathostome antibody was detected by a dot enzyme-linked immunosorbent assay (Dot ELISA) in the serum. He was diagnosed as gnathostomiasis, and was given albendazole 400 mg b.i.d. On day 11 of therapy the patient removed a larval worm from the right palmar lesion by pinching with his nails. The worm was identified as G. spinigerum based on morphologic characteristics including number of hooklets on its head-bulb. When gnathostomiasis is suspected, albendazole should be administered before incision of the skin lesion.

[Evaluation of the simultaneous detection system for Chlamydia trachomatis/Neisseria gonorrhoeae DNA by the isothermal and chimeric primer-initiated amplification of nucleic acids (ICAN)].

The isothermal and chimeric primer-initiated amplification of nucleic acids (ICAN) is a new isothermal DNA amplification method composed of exo Bca DNA polymerase, RNaseH and DNA-RNA chimeric primers. We developed the simultaneous detection system for Chlamydia trachomatis/Neisseria gonorrhoeae DNA, combined with luminescence detection by a probe hybridization. In the performance tests, this system was able to detect 10 to 100 copies of C. trachomatis/N. gonorrhoeae DNA for only 3.5 hours, and was highly specific to C. trachomatis/N. gonorrhoeae without any cross-reaction to C. pneumoniae, N. lactamica, N. sicca or N. meningitidis. When we tested 60 clinical samples of urine and cervical swabs, the interpretive results were completely consistent with those obtained by Roche PCR system. Of 13 positive samples by the ICAN and PCR systems for C. trachomatis, four were negative by EIA method(IDEIA Chlamydia). These results indicate that the ICAN system is an efficient and sensitive system to simultaneously detect C. trachomatis/N. gonorrhoeae DNA.

[Retrospective analysis of chief complaints of patients with urogenital malignancies over the past decade at the Jikei University Hospital].

We analyzed the chief complaints of patients with four major urogenital malignancies (renal cancer, renal pelvis and ureter cancer, bladder cancer and prostatic cancer) over the past decade (1990-1999) at the Jikei University Hospital. Over the last 10 years, a high percentage of renal cancers were detected incidentally. By contrast, prostatic cancers were more likely (10.5%) than other cancers to be detected on the basis of symptoms of metastasis. However, since 1995 more prostatic cancers are being detected with prostatic-specific antigen screening at the health checkups. Gross hematuria is the chief complaint of most patients with uroepithelial cancers (cancers of the renal pelvis, ureter and bladder cancer). Additionally, renal pelvis and ureter cancers were diagnosed with screening in a few patients in the past five years.

[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.

[Carcinoma of urachus: report of 15 cases and review of literature--is total cystectomy the treatment of choice for urachal carcinoma?].

PURPOSE: This study was undertaken to determine the most appropriate type of operation for the improvement of the radical cure rate and QOL of patients with urachal cancer. We assessed the association between the stage, type of operation, and prognosis of cases we experienced and those reported in Japan. PATIENTS AND METHOD: The subjects included 15 cases of urachal cancer we have experienced in the past 14 years. While clarifying the clinical patterns of these cases, the association between stage, type of operation, and prognosis was studied. Of the cases of urachal cancer reported in Japan in the recent 20 years, 75 cases in which the stage, type of operation, and prognosis were documented were selected, and the association between the stage and outcome in each type of operation was studied. RESULTS: In regard to stage, all the cases were rated as more than IIIA. As for prognosis, 9 cases (60%) are alive without cancer at the present time with a mean survival time of 7 years. Of the above patients, 3 underwent cystectomy and 6 underwent en bloc segmental resection (herein after referred to en bloc). Recurrence or cancer death was experienced in 5 patients, 2 of which were classified as stage IIIA and 3 as IIID. Of these patients, one underwent en bloc, 3 partial resection of the bladder, and one underwent exploratory laparotomy. As far as our study of the cases reported in Japan is concerned, the prognosis of the cases having undergone only partial resection of the bladder was poor, while of the cases having undergone en bloc or total cystectomy 88-100% were alive without cancer for more than 2 years if their stage was classified as IIIA or below. On the other hand, prognosis was very poor whatever the type of operation in the cases whose cancer was stage IIIC or above. CONCLUSIONS: It appears that the en bloc is most appropriate as the type of operation for the cases of urachal cancer and that the application of total cystectomy is limited to some cases. In performing the en bloc, an extensive resection of the peritoneum, resection of the posterior sheath of the rectus muscle of the abdomen, and dissection of the intrapelvic lymph nodes in addition to the conventional types of operation should be carried out positively.

Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis.

To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011-2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33). The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43) and 37.2% (16/43), respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50). The microbiological eradication rates for the pathogens were 90.9% (30/33) for Neisseria gonorrhoeae, 91.5% (43/47) for Chlamydia trachomatis, 71.4% (5/7) for Mycoplasma genitalium, and 100% (13/13) for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120). The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

An HIV patient with hepatic flare after the initiation of HBV-active antiretroviral therapy.

A 39-year-old man presented a CD4 T cell count of 78/µL and HIV-RNA at 6.6 × 10(5) copies/mL at his first medical examination. After the 58th day, we initiated HBV-active antiretroviral therapy. Three months after the start of antiretroviral therapy, he was diagnosed with hepatic flare on the basis of elevated AST and ALT levels without detecting HBV-DNA. Although after continuing the medication his AST and ALT levels increased to 700 IU/L and 1,400 IU/L, respectively, he showed improvement following a natural course and was discharged from hospital after the 169th day. This is a case of hepatic flare likely caused by immune reconstitution associated with resolved HBV infection.

Examination of the correlation between the manual and automated serological testing methods for syphilis.

We evaluated the correlation between the conventional manual serological testing method for syphilis and a novel automated serological testing method and between six different reagents used in the automated method. Twenty-six serum samples, which were positive on non-treponemal manual serological testing, were obtained from 19 patients with early syphilis. The samples were manually analyzed using the non-treponemal serological test for syphilis kit and automatically analyzed using six different reagents approved by the Ministry of Health, Labor and Welfare in Japan. Statistically significant correlations were observed between most of the reagents used in the automated testing (r = 0.652-0.996, P < 0.001), except for one combination of the reagents. In the simple regression analysis, the slope of the simple regression line (range, 0.014-3.040) and some of the regression coefficients were not equal to 1.0. Therefore, it is recommended that when the automated serological testing method is used to test for syphilis, the same reagent should be consistently selected to evaluate the changes in antibody titers. Statistically significant correlations were also observed between the manual method and all the reagents used in the automated method (r = 0.682-0.811, P < 0.001). In this case, the regression coefficients ranged 0.375-6.270, and the simple regression line intercept ranged -71.926 to 4.184. The regression coefficient and the intercept between the manual method and some of the reagents used in the automated method were not similar to the values described in the documentation attached to the reagents used in this study.