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Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were β-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan., Competing Interests: Declaration of competing interest Satoshi Takahashi received speaker honoraria from MSD K.K., Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K.K., Fujirebio Inc., and Abbott Japan Co., Ltd. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Hiroyuki Nishiyama received research funding from Chugai Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Junichi Inokuchi received research funding from Chugai Pharmaceutical Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Neisseria meningitidis causes invasive meningococcal diseases and has also been identified as a causative agent of sexually transmitted infections, including urethritis. Unencapsulated sequence type 11 meningococci containing the gonococcal aniA-norB locus and belonging to the United States N. meningitidis urethritis clade (US_NmUC) are causative agents of urethral infections in the United States, predominantly among men who have sex with men. We identified 2 subtypes of unencapsulated sequence type 11 meningococci in Japan that were phylogenetically close to US_NmUC, designated as the Japan N. meningitidis urethritis clade (J_NmUC). The subtypes were characterized by PCR, serologic testing, and whole-genome sequencing. Our study suggests that an ancestor of US_NmUC and J_NmUS urethritis-associated meningococci is disseminated worldwide. Global monitoring of urethritis-associated N. meningitidis isolates should be performed to further characterize microbiologic and epidemiologic characteristics of urethritis clade meningococci.

The objective of this study was to analyze the relationship between the pharmacokinetic (PK)/pharmacodynamic (PD) parameters of a single 2-g dose of extended-release formulation of azithromycin (AZM-SR) and its microbiological efficacy against gonococcal urethritis. Fifty male patients with gonococcal urethritis were enrolled in this study. In 36 patients, the plasma AZM concentrations were measured using liquid chromatography-tandem mass spectrometry, the AZM MIC values for the Neisseria gonorrhoeae isolates were determined, and the microbiological outcomes were assessed. AZM-SR monotherapy eradicated N. gonorrhoeae in 30 (83%) of the 36 patients. AZM MICs ranged from 0.03 to 2 mg/liter. The mean value of the area under the concentration-time curve (AUC), estimated by population PK analysis using a two-compartment model, was 20.8 mg · h/liter. Logistic regression analysis showed that the PK/PD target value required to predict an N. gonorrhoeae eradication rate of ≥95% was a calculated AUC/MIC of ≥59.5. The AUC/MIC value was significantly higher in patients who achieved microbiological cure than in patients who achieved microbiological failure. Monte Carlo simulation using this MIC distribution revealed that the probability that AZM-SR monotherapy would produce an AUC/MIC exceeding the AUC/MIC target of 59.5 was 47%. Furthermore, the MIC distribution for strains isolated in this study was mostly consistent with that for strains currently circulating in Japan. In conclusion, in Japan, AZM-SR monotherapy may not be effective against gonococcal urethritis. Therefore, use of a single 2-g dose of AZM-SR either with or without other antibiotics could be an option to treat gonococcal urethritis if patients are allergic to ceftriaxone and spectinomycin or are diagnosed to be infected with an AZM-sensitive strain., (Copyright © 2017 American Society for Microbiology.)

We determined minimum inhibitory concentrations (MICs) of 41 antimicrobial agents for 73 clinical strains of Haemophilus influenzae isolated from the urethra of men with acute urethritis and/or epididymitis and examined the strains for the production of β-lactamase. We also compared their antimicrobial susceptibilities with those of H. influenzae strains from respiratory tract or otorhinolaryngological infections that were reported in Japan. The proportion of β-lactamase-nonproducing ampicillin-resistant strains from acute urethritis and/or epididymitis appeared to be lower, but that of β-lactamase-producing ampicillin-resistant strains appeared to be higher, compared with those from respiratory tract or otorhinolaryngological infections. However, their antimicrobial susceptibilities to a variety of other antimicrobial agents would be similar to those from respiratory tract or otorhinolaryngological infections. Almost all of the strains of H. influenzae from acute urethritis and/or epididymitis were susceptible to the agents, including ceftriaxone, quinolones, macrolides, and tetracyclines, commonly prescribed for treatment of acute urethritis based on the MIC breakpoints recommended by the Clinical and Laboratory Standards Institute. Ceftriaxone and quinolones could be effective on H. influenzae-induced urethritis. However, azithromycin treatment failures were reported in acute urethritis caused by H. influenzae strains considered susceptible to azithromycin. Further studies will be needed to determine MIC breakpoints of antimicrobial agents, which are recommended for treatment of urogenital infections, for H. influenzae strains causing these infections. Nevertheless, this study provides useful data regarding antimicrobial susceptibilities of H. influenzae strains isolated from the urogenital tract, which have rarely been studied., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Worldwide, the most important concern in the treatment of sexually transmitted infections is the increase in antimicrobial resistant Neisseria gonorrhoeae strains including resistance to cephalosporins, penicillins, fluoroquinolones or macrolides. To investigate the trends of antimicrobial susceptibility among N. gonorrhoeae strains isolated from male patients with urethritis, a Japanese surveillance committee conducted the second nationwide surveillance study. Urethral discharge was collected from male patients with urethritis at 26 medical facilities from March 2012 to January 2013. Of the 151 specimens, 103 N. gonorrhoeae strains were tested for susceptibility to 20 antimicrobial agents. None of the strains was resistant to ceftriaxone, but the minimum inhibitory concentration (MIC) 90% of ceftriaxone increased to 0.125 μg/ml, and 11 (10.7%) strains were considered less susceptible with an MIC of 0.125 μg/ml. There were 11 strains resistant to cefixime, and the MICs of these strains were 0.5 μg/ml. The distributions of the MICs of fluoroquinolones, such as ciprofloxacin, levofloxacin and tosufloxacin, were bimodal. Sitafloxacin, a fluoroquinolone, showed strong activity against all strains, including strains resistant to other three fluoroquinolones, such as ciprofloxacin, levofloxacin and tosufloxacin. The azithromycin MICs in 2 strains were 1 μg/ml., (Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Six regional medical associations in Shiga prefecture agreed to cooperate in an investigation of medical care for male gonococcal and chlamydial urethritis. In June 2011, we sent a questionnaire to 372 medical offices in Shiga prefecture, and analyzed replies of respondents. Ten urologists and 175 non-urologists responded to the survey (response rate 49.7%). Among 185 physicians, 52 (10 urologists and 42 nonurologists) have treated male patients with gonococcal and chlamydial urethritis. More than 20% (42/175) of non-urological clinics are involved in the medical management. At initial diagnosis for sexually transmitted male urethritis, all urologists select the nucleic acid amplification method (100%), whereas many non-urologists do not (35%). For the treatment of chlamydial urethritis, non-urologists select levofloxacin (LVFX, 52.8%) rather than azithromycin (AZM, 22.0%), whereas urologists use AZM (78.0%) mostly but do not use LVFX (0%) (p = 0.023). For the treatment of gonococcal urethritis, non-urologists prefer oral new quinolones (53.1%) compared to urologists (25.0%) (p = 0. 74). For cure judgment of gonoccocal and chlamydial urethritis, many non-urologists rely on the improvement of subjective symptoms (50 and 47%), but urologists do not (10 and 0%) (p = 0.022 and 0.026, respectively). As for recognition of the clinical guideline for sexually transmitted disease, most urologists (90%) know it, but few non-urologists (13%) do (p < 0.001). We found that non-urological clinics make a great contribution to the medical treatment for male gonococcal and chlamydial urethritis in Shiga prefecture. It is important to standardize the medical care for sexually transmitted male urethritis by familiarizing non-urological practitioners with the clinical guideline.

Neisseria gonorrhoeae is one of the most important pathogens causing sexually transmitted infection, and strains that are resistant to several antimicrobials are increasing. To investigate the trends of antimicrobial susceptibility among N. gonorrhoeae strains isolated from male patients with urethritis, a Japanese surveillance committee conducted the first nationwide surveillance. The urethral discharge was collected from male patients with urethritis at 51 medical facilities from April 2009 to October 2010. Of the 156 specimens, 83 N. gonorrhoeae strains were tested for susceptibility to 18 antimicrobial agents. The prevalence of β-lactamase-producing strains and chromosomally mediated resistant strains were 7.2 % and 16.5 %, respectively. None of the strains was resistant to ceftriaxone, but the minimum inhibitory concentration (MIC) of ceftriaxone for 7 strains (8.4 %) was 0.125 μg/ml. One strain was resistant to cefixime (MIC 0.5 μg/ml). The MICs of fluoroquinolones, such as ciprofloxacin, levofloxacin, and tosufloxacin, showed a bimodal distribution. The MIC of sitafloxacin was lower than those of the three fluoroquinolones listed here, and it was found that the antimicrobial activity of sitafloxacin was stronger than that of the fluoroquinolones. The MIC of azithromycin in 2 strains was 2 μg/ml, but no high-level resistance to macrolides was detected.

The spread of antimicrobial-resistant Neisseria gonorrhoeae worldwide is a critical issue in the control of sexually transmitted infections. The purpose of this study was to clarify recent trends in the susceptibility of N. gonorrhoeae to various antimicrobial agents and to compare these data with our previous data. Minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined in N. gonorrhoeae strains clinically isolated from male gonococcal urethritis. In addition, amino acid sequencing of penicillin-binding protein (PBP) 2, encoded by the penA gene, was analyzed so that genetic analysis of mosaic PBP 2 could clarify the susceptibility of the strains to cefixime and other cephalosporins. The susceptibility rate for ceftriaxone, cefodizime, and spectinomycin, agents whose use is recommended by the guideline of the Japanese Society of Sexually Transmitted Infections (JSSTI), was 100 %. The susceptibility rates of the strains to penicillin G and ciprofloxacin were lower than those in previous reports. Mosaic PBP 2 structures were detected in 51.9 % of the strains and the MICs of the strains with the mosaic PBP 2 to cefixime were much higher than those of the strains without the mosaic PBP 2. In the clinical situation, the treatment regimen recommended by the JSSTI remains appropriate; however, the susceptibility to cephalosporins should be intensively surveyed because strains with mosaic PBP 2 were commonly detected.

To analyze the risk factors for HPV infection in the urethra, we examined the prevalence of various microorganisms, for example Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum, Gardnerella vaginalis, and human papillomavirus (HPV) in Japanese male patients with urethritis, and investigated their sexual backgrounds. Rubbed samples obtained from the distal urethra and questionnaires regarding sexual activity and demographic information were collected from 176 participants. N. gonorrhoeae, C. trachomatis, M. genitalium, M. hominis, U. urealyticum, U. parvum, G. vaginalis, and HPV were detected in 19, 26, 18, 12, 12, 8.5, 14, and 20%, respectively, of all cases in this study. Multivariate logistic regression analysis indicated that more than 4 sexual partners within the last year and presence of N. gonorrhoeae and/or C. trachomatis and/or M. genitalium infections were independent risk factors for urethral HPV infection, with odds ratios of 3.85 (95% CI 1.49-9.94) and 2.41 (95% CI 1.03-5.61), respectively. It is likely that urethral HPV detection is associated with current sexual activity and the presence of N. gonorrhoeae, C. trachomatis, and/or M. genitalium infections.

Surveillance for antimicrobial resistance in Mycoplasma genitalium clinical strains is extremely limited as culturing of strains from clinical specimens is still difficult. We therefore conducted a non-cultural assessment of fluoroquinolone resistance of M. genitalium clinical strains by analysing the quinolone-resistance determining regions (QRDRs) of the gyrA and parC genes. The QRDRs amplified from M. genitalium DNA taken from urine specimens of 28 men with non-gonococcal urethritis positive for M. genitalium by polymerase chain reaction were sequenced. An amino acid change (Phe-108-->Iso) in GyrA was found in one specimen, and the same change was accompanied by an amino acid change (Lys-97-->Arg) in ParC in another specimen. A single amino acid change (Ser-83-->Asn, Asp-87-->Tyr or Asp-87-->Val) in ParC was also found in three other respective specimens without alterations in GyrA. No alterations in GyrA and ParC were found in the remaining 23 specimens. The alterations of Ser-83-->Asn, Asp-87-->Tyr and Asp-87-->Val in ParC found in 3 (10.7%) of 28 specimens were analogous to those commonly observed in fluoroquinolone-resistant mutants of other Mycoplasma and Ureaplasma spp. M. genitalium harbouring mutations associated with fluoroquinolone resistance in the parC gene may have emerged clinically and the prevalence may be ca. 10% in Japan., (Copyright (c) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

In Japan, Neisseria meningitidis is not sufficiently recognized as the primary causative bacteria of sexually transmitted diseases (STDs) as the number of reported cases is small. Here, we summarize reports from 3 medical institutions, present clinical courses for each case, as well recommending precautions to prevent infection with this bacterium. Fourteen cases of N. meningitidis urethritis (MU) were admitted between April 2001 and June 2006. All patients were male, consulted a doctor after experiencing subjective symptoms, such as micturition pain and pus discharge, and were diagnosed as having urethritis using isolation culture methods. In 8 of the 14 cases, history of sexual contact in the preclinical stage was confirmed, and contact was with a commercial sex worker (CSW) in 6 of these cases. Many of these patients recalled oral contact. All strains indicated susceptibility to many drugs, and there were no problems with treatment. With regard to serotype, there were 10 cases of type Y, 1 case of type B, and 3 cases that were not classifiable or unidentified. In addition, among the 9 strains that were subjected to genotype identification, 7 strains were ST-23. The recent increase in availability of nucleic acid amplification methods has facilitated simultaneous detection of Neisseria gonorrhoeae and Chlamydia trachomatis. However, we fear that MU will become latent. For screening of urethritis, Gram staining and culture of urethral material must be performed to detect this disease. The relationship of the detected strain and its role in the pathogenesis of meningitis are uncertain, but its serotype and genotype are common in cases of meningitis. Thus, precautions are required to prevent spread of this bacterium.

Background: There are few studies on coinfection with genital mycoplasmas and ureaplasmas in men with gonococcal urethritis (GU). The role of these species in postgonococcal urethritis (PGU) is poorly understood. Thus, we conducted a study to determine the prevalence of coinfection with genital mycoplasmas and ureaplasmas among men with GU and to assess the role of these pathogens in PGU., Methods: Three hundred ninety men infected with culture-confirmed Neisseria gonorrhoeae participated in the study. Chlamydia trachomatis, Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum biovar 1, and Ureaplasma urealyticum biovar 2 in first-voided urine samples were detected by polymerase chain reaction-based assay at the patients' initial visits. PGU was judged to be present if the urethral smear was positive for polymorphonuclear leucocytes 7-14 days after treatment for gonorrhea. The association between each microorganism and PGU, measured by the odds ratio, was estimated by multivariate logistic regression analysis., Results: C. trachomatis, M. genitalium, M. hominis, U. parvum biovar 1, and U. urealyticum biovar 2 were detected in 85 (21.8%), 16 (4.1%), 8 (2.1%), and 33 men (8.5%), respectively. In patients with chlamydia-negative GU, coinfection with M. genitalium was associated with a 14.54-fold greater risk of PGU (95% confidence interval, 2.91-72.74), and coinfection with U. urealyticum biovar 2 was associated with a 3.64-fold greater risk of PGU (95% confidence interval, 1.24-10.63)., Conclusions: Coinfection with M. genitalium or U. ureaplasma biovar 2 in men with GU was significantly associated with PGU, independent of C. trachomatis. Men with GU should be treated presumptively with antibiotics that are active against C. trachomatis, M. genitalium, and U. urealyticum biovar 2.

Background: We previously reported a significant association between Ureaplasma urealyticum (biovar 2) and nongonococcal urethritis (NGU). We also found that the presence of Ureaplasma parvum (biovar 1) in the male urethra might be the result of colonization., Objective: The objective of this study was to clarify the pathogenic role of human Ureaplasma in NGU by assessing the association of bacterial loads with clinical findings and inflammatory responses in the urethra., Study Design: The 16S rRNA gene of Ureaplasma was quantified by a TaqMan-based real-time polymerase chain reaction assay in first-pass urine from 37 men with Ureaplasma-positive nonmycoplasmal nonchlamydial NGU (NMNCNGU) and 30 Ureaplasma-positive men without urethritis., Results: U. urealyticum (biovar 2) loads in 23 men with NMNCNGU were significantly higher than those in 14 men without urethritis. However, U. parvum (biovar 1) loads did not differ significantly between 14 men with NMNCNGU and 20 men without urethritis., Conclusion: The association of increased U. urealyticum (biovar 2) loads with symptomatic urethritis suggests that U. urealyticum (biovar 2) may be a pathogen of NGU. Our results also suggest that the presence of U. parvum (biovar 1) may not be significant in the development of NGU.

Isolation of Mycoplasma genitalium from clinical specimens remains difficult. We describe an improvement of the Vero cell coculture method in which the growth of M. genitalium was monitored by quantitative real-time PCR. Four new M. genitalium strains were isolated from six first-void urine specimens of male Japanese patients with urethritis. In two of them, only M. genitalium was detected: one also contained Ureaplasma urealyticum, and one contained Chlamydia trachomatis, Neisseria gonorrhoeae, U. urealyticum, and Ureaplasma parvum. In the specimens yielding isolates of M. genitalium, growth was documented by quantitative PCR after two to five passages in Vero cells. The complete isolation procedure from the initial inoculation to completion of single-colony cloning took about 1 year. Isolation of M. genitalium from urine specimens proved to be more difficult than from swab specimens. Due to the cytotoxic effect of urine, a procedure involving washing of the urinary sediment was introduced. Furthermore, prolonged storage of the urine specimens before culture was shown to be detrimental to the success of isolation, as shown by the lack of success in attempts to isolate M. genitalium from mailed urine specimens as well as by simulation experiments. High concentrations of penicillin G and amphotericin B were surprisingly inhibitory to the growth of wild-type M. genitalium strains, but penicillin G at 200 IU/ml and polymyxin B at 500 microg/ml could be used as selective antibiotics to avoid bacterial overgrowth in the Vero cell cultures.

Objectives: The objective of this study was to investigate the clinical features of non-gonococcal urethritis in men who attended a urological outpatient clinic in Japan., Materials and Methods: This study included a total of 194 patients diagnosed as having non-gonococcal urethritis and subsequently judged as cured following antibiotic therapy between January 2001 and June 2005. Clinical data were analyzed after dividing these patients into two groups as follows: 96 patients with chlamydial urethritis (CU) and 98 with non-chlamydial urethritis (NCU)., Results: The incubation period in the CU group was significantly longer than that in the NCU group (P = 0.0020). The incidence of severity of symptoms in the NCU group was significantly greater than that in the CU group (P = 0.022), and the interval between the appearance of the initial symptom and consulting the clinic was significantly shorter in the NCU group than in the CU group (P = 0.0015). The proportion of commercial sex workers (CSWs) as the causative partner in the NCU group was significantly greater that in the CU group (P < 0.001), and the incidence of oral sex as the causative mode of sexual interaction was significantly more frequent in the NCU group than that in the CU group (P = 0.021). The duration of antibiotic therapy until cured was significantly longer in the CU group than in the NCU group (P = 0.0051). Furthermore, multivariate analysis showed that whether the infection involved CU or NCU was independently associated with the treatment interval irrespective of other factors examined (P = 0.041)., Conclusions: These findings suggest that the clinical characteristics of CU and NCU clearly differ and that CU tends to require a longer time to cure than NCU; therefore, among patients with non-gonococcal urethritis, it would be particularly important to effectively control the spread of CU.

Aim: Trichomonas vaginalis may cause symptomatic or asymptomatic urethritis in men. There are few recent studies on the prevalence of T. vaginalis infection in Japanese men, and quantification of the number of cases of urethritis attributable to this pathogen has not been performed in Japan. The aim of this study was to determine the prevalence and morbidity of T. vaginalis infection in Japanese men., Methods: One hundred subjects with or without urethritis were examined for the presence of urethral T. vaginalis using culture swabs., Results: Urethral swabs from all subjects were negative for T. vaginalis., Conclusion: These results indicate Japanese men, including those with urethritis, have a low incidence of urethral T. vaginalis infection or colonization. T. vaginalis appears to be an uncommon pathogen for male urethritis in Japan.

Twenty-three clinical strains of Chlamydia trachomatis were isolated from men with chlamydial nongonococcal urethritis and examined for the presence of fluoroquinolone resistance-associated alterations in GyrA and ParC. The minimum inhibitory concentrations (MICs) of fluoroquinolones, erythromycin, and tetracycline were determined for 6 of the 23 isolates. In 12 of the 23 isolates, a single amino-acid change was found in GyrA, and in 1 isolate, two amino acids were changed. In all 23 isolates, an Arg-83-to-Gly substitution was observed in ParC, and in 3 isolates, an additional amino-acid change was found. Some changes occurred within the quinolone resistance-determining regions (QRDRs) of GyrA and ParC, but not at positions critical for fluoroquinolone resistance. Of the 6 isolates for which MICs of the agents were determined, 1 isolate had a Cys-66 --> Arg substitution in GyrA, and all had the Arg-83 --> Gly substitution in ParC. However, all 6 isolates were susceptible to fluoroquinolones. First-pass urine specimens were obtained from two men who were positive for C. trachomatis after levofloxacin treatment, and the gyrA and parC genes of C. trachomatis were amplified by polymerase chain reaction (PCR) and examined for fluoroquinolone resistance-associated mutations. Pre- and post-treatment C. trachomatis persisting in each of them had identical amino-acid sequences in the QRDR of GyrA and ParC. Further, the substitutions found in GyrA and ParC were not located at positions critical for fluoroquinolone resistance. The present study suggests that fluoroquinolone resistance-associated alterations in GyrA and ParC may be uncommon in clinical strains of C. trachomatis.

Aim: To use polymerase chain reaction (PCR)-microtiter plate hybridization assays to detect Mycoplasma genitalium, Mycoplasma hominis, Ureaplasma parvum (biovar 1) and Ureaplasma urealyticum (biovar 2) in first-voided urine specimens from patients with non-gonococcal urethritis (NGU)., Methods: A total of 153 male patients with NGU, who visited one of 24 clinics in Japan, were recruited for this study. All were examined using PCR-microtiter plate hybridization assays for the presence of M. genitalium, M. hominis, U. parvum (biovar 1) and U. urealyticum (biovar 2) in first-voided urine specimens. They were also examined for the presence of Chlamydia trachomatis., Results: Of these 153 patients, 73 (47.7%) were positive for C. trachomatis. Overall, the prevalence was 17.0% for M. genitalium, 16.3% for U. urealyticum (biovar 2), 7.8% for U. parvum (biovar 1) and 2.6% for M. hominis. In the 80 patients with non-chlamydial NGU, the prevalence of M. genitalium, U. urealyticum (biovar 2), U. parvum (biovar 1) and M. hominis was 23.8%, 18.8%, 8.8% and 2.6%, respectively., Conclusions: This study shows the prevalence of mycoplasmas and ureaplasmas in NGU in Japan. M. genitalium and U. urealyticum (biovar 2) might be pathogens of NGU and could be associated with persistent and recurrent urethritis. When patients with NGU are treated, such pathogens should be taken into account. This PCR-microtiter plate hybridization assay provides a useful method for diagnosing NGU caused by M. genitalium and U. urealyticum (biovar 2).

Background: The tiny (T)-strain mycoplasmas, designated in 1974 as Ureaplasma urealyticum, have been divided into 2 species, Ureaplasma parvum (biovar 1) and U. urealyticum (biovar 2), but association of each of these species with nongonococcal urethritis (NGU) remains unclear., Goal: The goal of this study was to determine whether U. parvum (biovar 1) or U. urealyticum (biovar 2) is associated with NGU., Study Design: The prevalences of U. parvum (biovar 1) and U. urealyticum (biovar 2) in 572 patients with urethritis were compared with those in 141 men without urethritis., Results: The prevalence of U. urealyticum (biovar 2) in men with NGU (15.8%) or with nonchlamydial NGU (18.0%) was significantly higher than that in men without urethritis (7.8%). The prevalence of U. parvum (biovar 1) in men with NGU (8.5%) or with nonchlamydial NGU (11.1%) did not differ significantly from that in men without urethritis (13.5%)., Conclusion: Our results showed a significant association between U. urealyticum (biovar 2) and NGU. They also suggest that the presence of U. parvum (biovar 1) in the male urethra might be the result of colonization.

Regarding Neisseria gonorrhoeae, the National Committee for Clinical Laboratory Standards (NCCLS) has not defined the breakpoint minimum inhibitory concentration (MIC) for expanded spectrum cephems such as cefpodoxime and ceftizoxime, because of the absence of resistant strains to these antibiotics. To date, in gonococcal urethritis, after treatment with third generation cephems and aztreonam, clinical failures caused by resistant N. gonorrhoeae strains have not been reported. However, we experienced two clinical failures in patients with gonococcal urethritis treated with cefdinir and aztreonam. N. gonorrhoeae isolates from these two patients showed high-level MICs to these agents. The MIC of cefdinir was 1 microg/ml for both strains and that of aztreonam was 8 microg/ml for both strains, while the MICs of other beta-lactams were also higher than the NCCLS value, except for ceftriaxone, for which the MIC was 0.125 microg/ml for both strains. Moreover, the MICs of fluoroquinolones, tetracyclines, and erythromycin against these two isolates were higher than the NCCLS susceptibility value. These isolates were susceptible to spectinomycin. In N. gonorrhoeae, the emergence of these beta-lactam-resistant isolates is of serious concern. However, a more serious problem is that these isolates were already resistant to non-beta-lactam antimicrobials. In Japan, ceftriaxone has not been permitted for clinical use against gonococcal infections. Therefore, in Japan, patients with gonococcal urethritis caused by these resistant N. gonorrhoeae strains should be treated with cefodizime or spectinomycin.

To assess the antimicrobial resistance of Neisseria gonorrhoeae isolated from 1993 through 1998 in Japan, susceptibility testing was conducted on 502 isolates. Selected isolates were characterized by auxotype and analysis for mutations within the quinolone resistance-determining region (QRDR) in the gyrA and parC genes, which confer fluoroquinolone resistance on the organism. Plasmid-mediated penicillin resistance (penicillinase-producing N. gonorrhoeae) decreased significantly from 1993-1994 (7.9%) to 1997-1998 (2.0%). Chromosomally mediated penicillin resistance decreased from 1993-1994 (12.6%) to 1995-1996 (1.9%) and then increased in 1997-1998 (10.7%). Chromosomally mediated tetracycline resistance decreased from 1993-1994 (3.3%) to 1997-1998 (2.0%), and no plasmid-mediated high-level tetracycline resistance was found. Isolates with ciprofloxacin resistance (MIC >/= 1 microg/ml) increased significantly from 1993-1994 (6.6%) to 1997-1998 (24.4%). The proline-requiring isolates were less susceptible to ciprofloxacin than the prototrophic or arginine-requiring isolates. Ciprofloxacin-resistant isolates contained three or four amino acid substitutions within the QRDR in the GyrA and ParC proteins.

Epidemiological studies on sexually transmitted diseases (STDs) in Saitama Prefecture, from 1989 through 1991, were performed and the following results were obtained. The number of patients was 1,833 (male: 1,532, female: 30) cases in 1989, 1,294 (male: 1,163, female: 131) cases in 1990, and 1,672 (male: 1,478, female: 149) cases in 1991. Male patients in their twenties or thirties were often affected by STDs. The order of frequency of STDs was roughly as follows; non-gonococcal and non-chlamydial urethritis, gonococcal urethritis, chlamydial rethritis, condyloma acuminatum, genital herpeic infection and syphilis. Concerning the criteria of the diagnosis on chlamydial urethritis, cases diagnosed by only clinical findings decreased markedly from 1989 through 1991, cases diagnosed by the combination of the antibody of C. trachomatis and clinical findings increased, and cases diagnosed by the detection of C. trachomatis were always about 70%. Male patients were mostly infected from prostitutes. Many patients with STDs were often infected in Taiwan, the Philippines, the Kingdom of Thailand and Republic of Korea.

Epidemiological and bacteriological studies on Neisseria gonorrhoeae isolated in Sapporo, Japan, in 1980 and 1991 performed and the following results were obtained. 1. The range of age in the patients infected with Neisseria gonorrhoeae tended to be younger than those in the whole country. 2. Male patients in the early 20s or younger with gonococcal urethritis were often infected by bon-professional females but those in their late 20s or older were often infected from professional females, for example prostitutes and hostesses. 3. The rate of professional females who were positive to gonococci reached 17.4% and young females in their teens with cervicitis had the highest morbidity rate of gonococci than those in the older females. 4. The latent period in gonococcal infections tended to become longer gradually. 5. The isolation rate of penicillinase producing Neisseria gonorrhoeae (PPNG) showed a peak of 23.9% (61/255) in 1985, but gradually declined thereafter and it was 3.7% (1/27) in 1991. 6. An investigation on auxotype showed a decline of proto and Pro-strains and an increase of AHU-strains in non-PPNG. And most of the PPNG belonged to proto or Pro-strains. 7. With the relationship between auxotype and sensitivity to AMPC, AHU-strains were more sensitive than proto or Pro-strains.

We reviewed 497 patients with male urethritis diagnosed between January, 1986 and March, 1989 at the Asama General Hospital. The incidence of gonococcal urethritis (GU) was 47.7%, and that of non-gonococcal urethritis (NGU) 52.3%. There was no difference in the age distribution between GU and NGU. Prostitutes were the most common source of the infection in both GU and NGU. Incubation periods were longer in NGU than in GU, statistically. Urethral discharge was the most common symptom. Purulent urethral discharge was seen more commonly than serous urethral discharge in GU. On the contrary, serous urethral discharge was more common in NGU. Penicillin-resistant gonococcus comprised 29.4% and mixed infection of the C. trachomatis existed 25.6% in GU. C. trachomatis was detected in 71.8% in NGU. In GU, new quinolones and penicillins were administered frequently. The effective rates 1 week after the administration were 80.6% and 83.3%, respectively. In NGU, new quinolones and minocycline were administered frequently. The effective rates were 70.4% and 85.3%, respectively. Ofloxacin (OFLX) showed the highest effective rate to NGU among the four new quinolones. The relapse rate for the two-week administration group was lower than that for the one-week-administration group, but the difference was not statistically significant.

The detection of C. trachomatis antigen in first-voided urine sediments has recently been achieved by means of IDEIA CHLAMYDIA (IDEIA, Novo Nordisk), an EIA kit using monoclonal antibodies. Therefore, this kit was used as a screening test to examine the infection rate of C. trachomatis in young adult men without symptoms. The titers of serum IgA and IgG antibodies to C. trachomatis were also determined. 1. Antigen detection from first-voided urine sediments of young adult men without urogenital symptoms (141 cases): The detection rate by IDEIA was 5.0% (7/141). Three of the 7 cases which were positive for antigen in first-voided urine sediments were reaffirmed as having asymptomatic C. trachomatis urethritis, since they were also revealed to have C. trachomatis in the urethra. 2. The positive rates of serum antibodies: The titers of serum antibody were determined in 128 cases out of the 141 cases. The positive rates of IgA and IgG were 6.3% (8/128) and 35.9% (46/128) respectively. The positive rates of IgA and IgG antibodies were significantly higher in cases with positive antigen in first-voided urine sediments than in those which were negative. These results indicate that this kit is useful for antigen detection. 3. The screening test revealed asymptomatic C. trachomatis infections in 5% of young adult men, suggesting the extensive spread of the infection. The screening test using first-voided urine sediments will be useful in public health.

The Plasmid DNA patterns of 22 penicillinase-producing Neisseria gonorrhoeae (PPNG) strains isolated from male patients with gonococcal urethritis in 1988 at Tokyo Metropolitan Taito Hospital were determined. The 3.3 megadalton plasmid, the so called the African type plasmid, was present in 3 isolates out of 22 PPNGs, all of which occurred with a conjugative 24.5 megadalton plasmid. 4.4 megadalton plasmid was present in 19 isolates out of 22 PPNGs, 5 of which occurred with a conjugative 24.5 megadalton plasmid. The infective sources of the 3 cases of the African type PPNGs were found as 1 from philippines and 2 from prostitutes, so called Soap Land Girl in Japan. And they suggests that the African type PPNGs are already common in Japan.