Papers - YASUDA Mitsuru

Second nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by Japanese Surveillance Committee from 2015 to 2016: antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus

Hayami H, Takahashi S, Ishikawa K, Yasuda M, Yamamoto S, Wada K, Kobayashi K, Hamasuna R, Minamitani S, Matsumoto T, Kiyota H, Tateda K, Sato J, Hanaki H, Masumori N, Nishiyama H, Miyazaki J, Fujimoto K, Tanaka K, Uehara S, Matsubara A, Ito K, Hayashi K, Kurimura Y, Ito S, Takeuchi T, Narita H, Izumitani M, Nishimura H, Kawahara M, Hara M, Hosobe T, Takashima K, Chokyu H, Matsumura M, Ihara H, Uno S, Monden K, Sumii T, Kawai S, Kariya S, Sato T, Yoshioka M, Kadena H, Matsushita S, Nishi S, Hosokawa Y, Shirane T, Yoh M, Watanabe S, Makinose S, Uemura T, Goto H

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 6 ) 413 - 422  2019.06  [Refereed]

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非淋菌性尿道炎の治療効果判定における初尿白血球濃度の有用性

伊藤 晋, 安田 満, 花岡 希, 出口 隆

日本泌尿器科学会総会 ( (一社)日本泌尿器科学会総会事務局 )  107回   AOP - 037  2019.04

2015〜2017年にわが国で分離された淋菌の薬剤感受性について

安田 満, 籏崎 恭子, 小林 寅哲, 大澤 佳代, 濱砂 良一, 荒川 創一, 志牟田 健, 中山 周一, 大西 真, 陳内 理生, 三宅 啓文

日本化学療法学会雑誌 ( (公社)日本化学療法学会 )  67 ( Suppl.A ) 240 - 240  2019.03

2017年に男子淋菌性尿道炎患者より分離された淋菌の薬剤感受性について

安田 満, 伊東 晋, 楊 睦正, 伊藤 雅康, 西村 昌宏, 川原 元司, 平山 英雄, 宮田 和豊, 出口 隆, 田中 香お里, 村上 啓雄, 旗崎 恭子, 鷺山 和幸, 小島 宗門, 松木 孝和, 成田 晴紀, 木戸 雅人, 伊東 健治, 川井 修一, 上床 典康, 花井 俊典, 重原 一慶, 中嶋 一史, 沼崎 進, 内田 千秋, 竹内 敏視, 佐藤 嘉一, 楠山 弘之, 岩澤 晶彦, 野口 武俊, 土屋 博, 川野 尚, 小林 峰男, 山田 拓己, 内島 豊, 宮村 隆三, 米田 尚生, 久保田 恵章, 伊藤 康久, 岡野 学, 濱野 公成, 増栄 成泰

感染症学雑誌 ( (一社)日本感染症学会 )  93 ( 2 ) 235 - 236  2019.03  [Refereed]

A real-time PCR assay for detecting a penA mutation associated with ceftriaxone resistance in Neisseria gonorrhoeae.

Shimuta K, Igawa G, Yasuda M, Deguchi T, Nakayama SI, Ohnishi M

Journal of global antimicrobial resistance ( Elsevier BV )  19   46 - 49  2019.02  [Refereed]

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Etiological role of human papillomavirus infection in the development of penile cancer.

Jiro Sakamoto, Kazuyoshi Shigehara, Kazufumi Nakashima, Shohei Kawaguchi, Takao Nakashima, Masayoshi Shimamura, Mitsuru Yasuda, Taku Kato, Toru Hasegawa, Yoshitomo Kobori, Hiroshi Okada, Takashi Deguchi, Kouji Izumi, Yoshifumi Kadono, Atsushi Mizokami

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases   78   148 - 154  2019.01  [International journal]

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OBJECTIVE: To examine the association between human papillomavirus (HPV) infection and penile cancer among Japanese patients. METHODS: Thirty-four patients with penile cancer were enrolled in this study. DNA was extracted from paraffin-embedded tumor tissue samples, and HPV-DNA tests and genotyping were performed. For all of the samples, in situ hybridization (ISH) was performed to locate HPV-DNA in tumor tissue. Furthermore, expression levels of p16-INK4a, mini-chromosome maintenance protein 7(mcm-7), HPV-L1, and Ki-67 were analyzed using immunohistochemical methods. RESULTS: HPV and high-risk (HR)-HPV were detected in 14 (41.1%; 95% confidence interval (CI) 24.6-57.7%) and 12 (35.2%; 95% CI 19.2-51.4%) cases, respectively. HPV16 was the most frequently detected HPV type. Among the HR-HPV-positive cases, a punctate HR-HPV-DNA signal pattern was detected by ISH in tumor cell nuclei. P16-INK4a was expressed in 66.7% (95% CI 42.8-90.1%) of HR-HPV-positive cases and was significantly more frequent and stronger in HR-HPV-positive cases than in HPV-negative cases. There was no significant difference in the occurrence or distribution of mcm-7 or Ki-67 expression between HPV-positive and HPV-negative cases. HPV-L1 expression was not observed in any of the cases examined. CONCLUSIONS: HPV infection may have had an etiological role in 41% of the examined cases of penile cancer in Japan.

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Infectious human adenoviruses are shed in urine even after disappearance of urethral symptoms.

Nozomu Hanaoka, Shin Ito, Masami Konagaya, Naomi Nojiri, Mitsuru Yasuda, Tsuguto Fujimoto, Takashi Deguchi

PloS one   14 ( 3 ) e0212434  2019  [International journal]

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BACKGROUND: Urethritis is a common sexually transmitted disease, and human adenoviruses (HAdVs) have been found to be associated with nonchlamydial nongonococcal urethritis. However, the level and viability of HAdV in the urine of patients with urethritis remain unclear. METHODS: Male patients with urethritis and an asymptomatic group were screened using their First-void urine (FVU) for urethritis-related pathogens to identify those with HAdV DNA. FVU and gargle fluid were collected from all patients including from those in the asymptomatic group. A swab of eye discharge was also collected from patients with eye symptoms. The pharyngeal and/ or ocular fluid was also screened only in cases in which FVU was positive for HAdV DNA. HAdVs were isolated using A549 cell lines and typed by sequencing, and viral shedding during 2 years was quantified using real-time PCR. The prevalence of HAdV was assessed in the urethritis and asymptomatic groups, and viral load, isolated HAdV types, and urethral symptoms were compared between the groups. RESULTS: The positive detection rate of HAdV DNA was significantly higher in the urethritis group than in the asymptomatic group. Of 398 patients with urethritis, HAdV was isolated in all 32 cases (23 cases in which only HAdV DNA was detected with a mean of 2 × 109 copies/mL in urine samples). Of 124 control cases, one had HAdV monoinfection. The most frequently detected HAdV type was 56, followed by types 37 and 64. Regarding the relationship between symptoms and isolated HAdVs, the virus was isolated for up to 12 days after urethritis symptoms disappeared. CONCLUSIONS: HAdVs were significantly detected and isolated from the FVU of patients with urethritis. Furthermore, high levels of infectious HAdVs are excreted in urine for a long period even after urethritis symptoms disappear.

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Surveillance of the prevalence of macrolide and/or fluoroquinolone resistance-associated mutations in Mycoplasma genitalium in Japan

Takashi Deguchi, Shin Ito, Mitsuru Yasuda, Yuko Sato, Chiaki Uchida, Masayuki Sawamura, Kazushi Manda, Masaki Takanashi, Hiroshi Kiyota

Journal of Infection and Chemotherapy ( Elsevier B.V. )  24 ( 11 ) 861 - 867  2018.11

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To clarify the status of macrolide and fluoroquinolone resistance of clinical strains of Mycoplasma genitalium in Japan, we amplified portions of the gyrA, parC, and 23S rRNA genes from DNAs in 627 first-voided urine specimens collected from men with M. genitalium-positive urethritis who visited clinics mainly in Sendai, Tokyo, and Osaka, Japan, from 2013 to 2017, by PCR and sequenced. The incidence of single amino acid changes at Met95 or Asp99 in GyrA increased chronologically and was approximately 10% from 2015 onward. The incidence of amino acid changes at Ser83 or Asp87 in ParC was approximately 50% in 2013 but increased to 60–70% from 2014 to 2017. The incidence of mutations at A2071 or A2072 in the 23S rRNA gene increased chronologically and reached over 70% in 2017. The prevalence of M. genitalium harboring alterations in ParC and mutations in the 23S rRNA gene increased and was approximately 50% in 2016 and 2017. The prevalence of M. genitalium with alterations in both GyrA and ParC and mutations in the 23S rRNA gene, which could be associated with treatment failures with the sitafloxacin and azithromycin regimens, were approximately 15% and 10% in 2016 and 2017, respectively. The prevalence of M. genitalium with genetic alterations associated with resistance to fluoroquinolones and/or macrolides is increasing rapidly in Japan. We must prevent the further selection of multi-drug-resistant M. genitalium so that M. genitalium infections will not become untreatable.

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2015〜2017年にわが国で分離された淋菌の薬剤感受性報告

安田 満, 志牟田 健, 中山 周一, 小林 寅哲, 大澤 佳代, 陣内 理生, 三宅 啓文, 濱砂 良一, 荒川 創一, 大西 真

日本性感染症学会誌 ( (一社)日本性感染症学会 )  29 ( 2 ) 239 - 239  2018.10

尿道炎原因微生物の診断に関する検討 迅速免疫クロマトキットを用いたヒトアデノウイルスおよび単純ヘルペスウイルスの検出

伊藤 晋, 花岡 希, 伊藤 貴子, 安田 満, 出口 隆

日本性感染症学会誌 ( (一社)日本性感染症学会 )  29 ( 2 ) 241 - 241  2018.10

尿道炎原因微生物の診断に関する検討 原因微生物と排尿痛の程度

伊藤 晋, 伊藤 貴子, 花岡 希, 安田 満, 出口 隆

日本性感染症学会誌 ( (一社)日本性感染症学会 )  29 ( 2 ) 240 - 240  2018.10

尿道炎原因微生物の診断に関する検討 原因微生物と潜伏期間

伊藤 晋, 伊藤 貴子, 花岡 希, 安田 満, 出口 隆

日本性感染症学会誌 ( (一社)日本性感染症学会 )  29 ( 2 ) 240 - 240  2018.10

Corrigendum: Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages.

Koji Yahara, Shu-Ichi Nakayama, Ken Shimuta, Ken-Ichi Lee, Masatomo Morita, Takuya Kawahata, Toshiro Kuroki, Yuko Watanabe, Hitomi Ohya, Mitsuru Yasuda, Takashi Deguchi, Xavier Didelot, Makoto Ohnishi

Microbial genomics   4 ( 9 )  2018.09  [International journal]

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Macrolide and fluoroquinolone resistance is uncommon in clinical strains of Chlamydia trachomatis.

Deguchi T, Hatazaki K, Ito S, Kondo H, Horie K, Nakane K, Mizutani K, Tsuchiya T, Yasuda M, Yokoi S, Nakano M

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   24 ( 8 ) 610 - 614  2018.08  [Refereed]

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Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages.

Koji Yahara, Shu-Ichi Nakayama, Ken Shimuta, Ken-Ichi Lee, Masatomo Morita, Takuya Kawahata, Toshiro Kuroki, Yuko Watanabe, Hitomi Ohya, Mitsuru Yasuda, Takashi Deguchi, Xavier Didelot, Makoto Ohnishi

Microbial genomics   4 ( 8 )  2018.08  [Refereed]  [International journal]

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The first extensively drug resistant (XDR) Neisseria gonorrhoeae strain with high resistance to the extended-spectrum cephalosporin ceftriaxone was identified in 2009 in Japan, but no other strain with this antimicrobial-resistance profile has been reported since. However, surveillance to date has been based on phenotypic methods and sequence typing, not genome sequencing. Therefore, little is known about the local population structure at the genomic level, and how resistance determinants and lineages are distributed and evolve. We analysed the whole-genome sequence data and the antimicrobial-susceptibility testing results of 204 strains sampled in a region where the first XDR ceftriaxone-resistant N. gonorrhoeae was isolated, complemented with 67 additional genomes from other time frames and locations within Japan. Strains resistant to ceftriaxone were not found, but we discovered a sequence type (ST)7363 sub-lineage susceptible to ceftriaxone and cefixime in which the mosaic penA allele responsible for reduced susceptibility had reverted to a susceptible allele by recombination. Approximately 85 % of isolates showed resistance to fluoroquinolones (ciprofloxacin) explained by linked amino acid substitutions at positions 91 and 95 of GyrA with 99 % sensitivity and 100 % specificity. Approximately 10 % showed resistance to macrolides (azithromycin), for which genetic determinants are less clear. Furthermore, we revealed different evolutionary paths of the two major lineages: single acquisition of penA X in the ST7363-associated lineage, followed by multiple independent acquisitions of the penA X and XXXIV in the ST1901-associated lineage. Our study provides a detailed picture of the distribution of resistance determinants and disentangles the evolution of the two major lineages spreading worldwide.

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Oral administration of cernitin pollen extract (Cernilton^® ) for 30 days might be useful to avoid unnecessary biopsy in prostate biopsy candidates: A preliminary study.

Togo Y, Ichioka D, Miyazaki J, Maeda Y, Kameyama K, Yasuda M, Hiyama Y, Takahashi S, Nagae H, Hirota S, Yamamoto S, Japanese Research Group for Urinary Tract Infection (JRG

International journal of urology : official journal of the Japanese Urological Association   25 ( 5 ) 479 - 485  2018.05  [Refereed]  [International journal]

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OBJECTIVES: To assess the effect of cernitin pollen extract on serum prostate-specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure. METHODS: A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate-specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate-specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer. RESULTS: The mean change in serum prostate-specific antigen and rate of change after administration of cernitin pollen extract in all patients were -0.6 ± 1.4 ng/mL and -7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate-specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.

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GyrA and/or ParC alterations of Haemophilus influenzae strains isolated from the urethra of men with acute urethritis.

Kondo H, Ito S, Hatazaki K, Horie K, Nakane K, Mizutani K, Tsuchiya T, Yasuda M, Yokoi S, Nakano M, Deguchi T

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   24 ( 3 ) 232 - 235  2018.03  [Refereed]

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Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended-Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese Patients with Gonococcal Urethritis.

Soda M, Ito S, Matsumaru N, Nakamura S, Nagase I, Takahashi H, Ohno Y, Yasuda M, Yamamoto M, Tsukamoto K, Itoh Y, Deguchi T, Kitaichi K

Antimicrobial agents and chemotherapy   62 ( 1 )  2018.01  [Refereed]  [International journal]

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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.

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'Haemophilus quentini' in the urethra of men complaining of urethritis symptoms

Kengo Horie, Shin Ito, Kyoko Hatazaki, Mitsuru Yasuda, Masahiro Nakano, Kyojiro Kawakami, Yasunori Fujita, Masafumi Ito, Takayuki Ezaki, Takashi Deguchi

JOURNAL OF INFECTION AND CHEMOTHERAPY ( ELSEVIER SCIENCE BV )  24 ( 1 ) 71 - 74  2018.01  [Refereed]

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We isolated a cryptic genospecies of Haemophilus influenzae referred to as 'Haemophilus quentini' in the urethra of 3 men complaining of urethritis symptoms. H. influenzae strains, which had been isolated from the urethra in 77 of 1518 men complaining of urethritis symptoms, identified by the conventional test, and stored, were re-cultured for this study. Sixty-seven strains surviving storage were screened by a PCR-based assay specific for the cryptic genital Haemophilus genospecies. Three strains (HI09003, HI11006, and HI14016) were screened by PCR and identified as 'H. quentini' by 16S rRNA sequencing. The men positive for HI09003 and HI11006 were diagnosed as having non-chlamydial non-gonococcal urethritis (NGU), and their demographic and clinical features were similar to those of NGU caused by other pathogens. The man positive for HI14016 was ultimately diagnosed as having condyloma acuminatum on the glans. The 3 strains of 'H. quentini' produced no b-lactamase and were susceptible to ampicillin and other antimicrobial agents, including cephalosporins, fluoroquinolones, tetracyclines, and macrolides, recommended for treatment for urethritis. 'H. quentini' would be an uncommon pathogen in men with urogenital infections. Based on the clinical features of the two patients with 'H. quentini'-positive NGU, it would be difficult to predict the presence of 'H. quentini' in the urethra. The 3 strains of 'H. quentini' were susceptible to a variety of antimicrobial agents. Further accumulation of data regarding 'H. quentini' infections is needed to characterize the pathogenic roles of this genospecies in urogenital infections and to establish appropriate management of 'H. quentini' infections. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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Antimicrobial susceptibility of Haemophilus influenzae strains isolated from the urethra of men with acute urethritis and/or epididymitis

Takashi Deguchi, Shin Ito, Kyoko Hatazaki, Kengo Horie, Mitsuru Yasuda, Keita Nakane, Kosuke Mizutani, Tomohiro Tsuchiya, Shigeaki Yokoi, Nozomu Hanaoka, Ken Shimuta, Makoto Ohnishi, Tetsuro Muratani, Masahiro Nakano

JOURNAL OF INFECTION AND CHEMOTHERAPY ( ELSEVIER SCIENCE BV )  23 ( 11 ) 804 - 807  2017.11  [Refereed]

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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 beta-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 beta-lactamase-nonproducing ampicillin-resistant strains from acute urethritis and/or epididymitis appeared to be lower, but that of beta-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. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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