Faculty Profiles - ISHII Ayano

Papers - ISHII Ayano

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Exploration of the protein-dependent mechanism of Lactobacillus crispatus GAI98322 to prevent recurrent cystitis. Reviewed International journal

Tomofumi Watanabe, Takuya Sadahira, Hidetada Hirakawa, Peng Huang, Tianyun Zhou, Takehiro Iwata, Takanori Sekito, Ayano Ishii, Masami Watanabe, Motoo Araki

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 29 ( 10 ) 1001 - 1004 2023.6

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To elucidate the mechanism of Lactobacillus crispatus (L. crispatus) suppositories to prevent patients from recurrent cystitis (RC), independent from viable-Lactobacilli-bacteria- and acid-dependent ones such as hydrogen peroxide and lactate. METHODS: We used the GAI98322 strain of L. crispatus in all experiments and pH-matched. cell-free culture supernatant of L. crispatus (CFCS) was collected. The growth inhibitory activity and the biofilm formation inhibitory activity of the CFCS against uropathogenic Escherichia coli (UPEC), Extended Spectrum beta (β) Lactamase producing (ESBL+) UPEC, and Pseudomonas aeruginosa (P. aeruginosa) was assessed by agar-disk diffusion tests and crystal violet assay. Also, CFCS was subjected to mass spectrometry to specify ingredients. RESULTS: The CFCS suppressed the proliferation of E. coli, ESBL + E. coli, and P. aeruginosa. Also, the CFCS at a concentration of 40% significantly impeded the biofilm formation of these three bacteria. The aggregation-promoting factor and Lysin was detected from CFCS. CONCLUSIONS: The cell-free supernatant from the GAI98322 strain of L. crispatus inhibits the growth/biofilm formation of broad pathogens by aggregation promoting factor and lysin, which may prevent hosts from RC regardless of the antimicrobial resistance of the pathogens and even under pH modulation.

DOI： 10.1016/j.jiac.2023.06.013

Etiology of recurrent cystitis in postmenopausal women based on vaginal microbiota and the role of Lactobacillus vaginal suppository. Reviewed International journal

Takanori Sekito, Koichiro Wada, Ayano Ishii, Takehiro Iwata, Takehiro Matsubara, Shuta Tomida, Masami Watanabe, Motoo Araki, Takuya Sadahira

Frontiers in microbiology 14 1187479 - 1187479 2023.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The vaginal microbiota can be altered by uropathogenic bacteria associated with recurrent cystitis (RC), and the vaginal administration of Lactobacillus have suggested certain effects to prevent RC. The relationship between vaginal microbiota and the development of RC has not been elucidated. We aimed to clarify the etiology of RC from vaginal microbiota and importance of vaginal Lactobacillus. METHODS: Vaginal samples obtained from 39 postmenopausal women were classified into four groups: healthy controls; uncomplicated cystitis; RC; and prevention (prevented RC by Lactobacillus crispatus-containing vaginal suppositories). Principal coordinate analysis and beta-diversity analysis was used to assess 16S rRNA gene sequencing data from the vaginal microbiome. RESULTS: Cluster analysis divided the vaginal bacterial communities among 129 vaginal samples into three clusters (A, B, and C). Fourteen of 14 (100%) samples from the RC group and 51 of 53 (96%) samples from the prevention group were in clusters B and C, while 29 of 38 (76%) samples from the healthy group and 14 of 24 (58%) samples from the uncomplicated cystitis group were in cluster A. The principal coordinate analysis showed that plots in the uncomplicated cystitis group were similar to the healthy group, indicating a large separation between the RC group and the uncomplicated cystitis group. On beta-diversity analysis, there were significant differences between the healthy group and the uncomplicated cystitis group (p = 0.045), and between the RC group and the uncomplicated cystitis group or the healthy group (p = 0.001, p = 0.001, respectively). There were no significant differences between the RC group and the prevention group (p = 0.446). The top six taxa were as follows: Prevotella, Lactobacillus, Streptococcus, Enterobacteriaceae, Anaerococcus, and Bifidobacterium. Among patients with RC, Lactobacillus was undetectable before administration of suppositories, while the median relative abundance of Lactobacillus was 19% during administration of suppositories (p = 0.0211), reducing the average cystitis episodes per year (6.3 vs. 2.4, p = 0.0015). CONCLUSION: The vaginal microbiota of postmenopausal women with RC is differed from healthy controls and uncomplicated cystitis in terms of lack of Lactobacillus and relatively dominant of Enterobacteriaceae. Vaginal administration of Lactobacillus-containing suppositories can prevent RC by stabilizing vaginal dysbiosis and causing a loss of pathogenic bacteria virulence.

DOI： 10.3389/fmicb.2023.1187479

Efficacy of Lactobacillus vaginal suppositories for the prevention of recurrent cystitis: A phase II clinical trial. Reviewed International journal

Takuya Sadahira, Koichiro Wada, Motoo Araki, Ritsuko Mitsuhata, Masumi Yamamoto, Yuki Maruyama, Takehiro Iwata, Masami Watanabe, Toyohiko Watanabe, Reiko Kariyama, Yasutomo Nasu, Ayano Ishii

International journal of urology : official journal of the Japanese Urological Association 28 ( 10 ) 1026 - 1031 2021.10

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To prospectively assess the efficacy and safety of Lactobacillus vaginal suppositories for the prevention of recurrent cystitis. METHODS: In this single-arm, open-label, phase II clinical trial, participants used vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus for 1 year either every 2 days or three times per week. The primary end-point was the response rate, as assessed by the number of episodes of recurrent cystitis during the year of administration. The secondary end-points were the response rate, as assessed by episodes of recurrent cystitis during the 1 year after completion of the administration period; the total number of episodes of recurrent cystitis before, during and after administration; adverse events; and changes in urine bacteria and the vaginal microbiome. RESULTS: A total of 28 women were enrolled, and 21 completed the study. A total of 18 patients achieved an effective response (86%) during administration. The suppressive effects of Lactobacillus vaginal suppositories on episodes of cystitis continued up to 1 year after the last suppository was administered. There was a significant reduction in the mean number of episodes of cystitis, both during and after administration of Lactobacillus vaginal suppositories. No treatment-related adverse events were observed. Amplicon sequencing analysis of the vaginal microbiome showed that Lactobacillus species colonized the vagina during the periods when episodes of cystitis were absent. CONCLUSIONS: Vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus effectively prevent episodes of recurrent cystitis, both during administration and for at least 1 year after administration.

DOI： 10.1111/iju.14636

Preventive efficacy and safety of lactobacillus vaginal suppositories in women with recurrent cystitis: A phase 2 study Reviewed

Sadahira T, Wada K, Ishii A, Maruyama Y, Iwata T, Araki M, Watanabe M, Watanabe T, Nasu Y

Eur Urol Open Sci 19 ( 2 ) 2036 - 2037 2020

女性過活動膀胱に対する牛車腎気丸の効果と冷えとの関係について Reviewed

松本裕子, 石井亜矢乃, 山本満寿美, 松尾聡子, 佐古智子, 荒木元朗, 渡邉豊彦, 那須保友, 井上雅, 荒木詞奈子, 石戸則孝, 高本均

西日本泌尿器科 81 ( 1 ) 12 - 16 2019.2

Authorship：Corresponding author Language：Japanese Publisher：西日本泌尿器科学会

牛車腎気丸には過活動膀胱症状を改善する効果があることが知られているが、末梢血流増加作用もある。女性過活動膀胱に対し牛車腎気丸を投与し、治療効果と冷えとの関係を検討した。成人女性過活動膀胱患者56例を対象とし、TJ-107ツムラ牛車腎気丸エキス顆粒(牛車腎気丸)1日7.5gを分3で4週間投与し、治療前、治療4週目に過活動膀胱質問票(Overactive Bladder Symptom Score;OABSS)、冷えに関する質問票で症状を確認し、非接触型赤外線温度計で体表温度(手掌、恥骨上、足蹠)を測定した。他の過活動膀胱治療薬を内服している場合は変更せず継続した。平均年齢は35〜90歳(平均64.1±13.8歳)で、OABSSは治療前7.57±3.36、後6.73±3.50と有意に改善した(p=0.006)。治療前後で体表温度の有意な上昇はみられなかったが、治療前に冷えを自覚した36例(64.3%、平均65.1±13.8歳)ではOABSSが治療前7.94±3.65、後6.86±3.61と有意に改善し(p=0.004)、治療前に冷えを自覚しなかった20例(35.7%、平均62.3±13.6歳)では改善傾向はあったが有意差はなかった。このことから、治療前に冷えの自覚があるほうが、自覚のない症例に比べて牛車腎気丸による治療効果が期待でき、治療の指標になりうると考えられた。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J01004&link_issn=&doc_id=20190222240003&doc_link_id=%2Fer9niuro%2F2019%2F008101%2F003%2F0012-0016%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer9niuro%2F2019%2F008101%2F003%2F0012-0016%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

A Phase II Clinical Trial Evaluating the Preventive Effectiveness of Lactobacillus Vaginal Suppositories in Patients with Recurrent Cystitis

Koichiro Wada, Shinya Uehara, Ayano Ishii, Takuya Sadahira, Masumi Yamamoto, Ritsuko Mitsuhata, Atsushi Takamoto, Motoo Araki, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Katsuyuki Hotta, Yasutomo Nasu

ACTA MEDICA OKAYAMA 70 ( 4 ) 299 - 302 2016.8

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

Urinary tract infections (UTIs) are the most common bacterial infections in women, and many patients experience frequent recurrence. The aim of this report is to introduce an on-going prospective phase II clinical trial performed to evaluate the preventive effectiveness of Lactobacillus vaginal suppositories for prevention of recurrent cystitis. Patients enrolled in this study are administered vaginal suppositories containing the GAI 98322 strain of Lactobacillus crispatus every 2 days or 3 times a week for one year. The primary endpoint is recurrence of cystitis and the secondary endpoints are adverse events. Recruitment began in December 2013 and target sample size is 20 participants.

DOI： 10.18926/AMO/54508

Homology of Escherichia coli isolated from urine and vagina and their antimicrobial susceptibility in postmenopausal women with recurrent cystitis. Reviewed International journal

Takanori Sekito, Takuya Sadahira, Hidetada Hirakawa, Ayano Ishii, Koichiro Wada, Motoo Araki

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 30 ( 10 ) 1081 - 1084 2024.3

Language：English Publishing type：Research paper (scientific journal)

Uropathogenic Escherichia coli (UPEC) is a typical cystitis-causing organism that can migrate from the vagina to the bladder and cause recurrent cystitis (RC). Few reports have compared the characteristics of urinary and vaginal UPEC in patients with RC. We carried out molecular biological analyses of Escherichia coli (E. coli) strains and their antimicrobial susceptibility to assess the association between urinary and vaginally UPEC. We included E. coli isolated from urinary and vaginal samples at the onset of cystitis in postmenopausal women with RC between 2014 and 2019 in our hospital. Pulsed-field gel electrophoresis (PFGE) was performed using a restriction enzyme (Xba I). These sequences were compared with 17 antimicrobial susceptibilities determined by a micro-liquid dilution method. Multilocus sequence typing (MLST) and classification of extended-spectrum β-lactamase (ESBL) genotypes by multiplex polymerase chain reaction (PCR) were performed on ESBL-producing E. coli. We analyzed 14 specimens (each seven urine and vaginal) from seven patients in total. On PFGE, the similarity of urinary and vaginal E. coli per patient ranged from 89.5 to 100%, including four patients with 100% matches. MLST demonstrated that 29% (4/14 specimens) were strain sequence type 131. Two specimens contained ESBL-producing strains and identified the CTX-M-27 genotype for each specimen. For each patient, antimicrobial susceptibilities between urinary and vaginal E. coli were mostly identical. Thus, urinary- and vaginally-derived E. coli were identical in postmenopausal women with RC. Management targeting both urinary and vaginal UPEC is essential for RC, indicating the importance of a vagina-targeted approach.

DOI： 10.1016/j.jiac.2024.05.015

Clinical Efficacy and Safety of Sitafloxacin 200 mg Once Daily for Refractory Genitourinary Tract Infections. Reviewed

Takehiro Iwata, Takuya Sadahira, Yuki Maruyama, Takanori Sekito, Kasumi Yoshinaga, Shogo Watari, Kentaro Nagao, Tatsushi Kawada, Yusuke Tominaga, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Motoo Araki, Ayano Ishii, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu, Koichiro Wada

Acta medica Okayama 75 ( 6 ) 763 - 766 2021.12

Language：English Publishing type：Research paper (scientific journal)

The aim of this ongoing trial is to evaluate the clinical efficacy and safety of sitafloxacin (STFX) 200 mg once daily (QD) for 7 days in patients with refractory genitourinary tract infections, which include recurrent or complicated cystitis, complicated pyelonephritis, bacterial prostatitis, and epididymitis. The primary endpoint is the microbiological efficacy at 5-9 days after the last administration of STFX. Recruitment began in February 2021, and the target total sample size is 92 participants.

DOI： 10.18926/AMO/62820

【これから始めるロボット支援下仙骨腟固定術】ロボット支援下仙骨腟固定術の導入に向けて Reviewed

佐古智子, 岩田健宏, 西村慎吾, 高本篤, 和田耕一郎, 枝村康平, 小林泰之, 荒木元朗, 石井亜矢乃, 渡邉豊彦, 那須保友

Japanese Journal of Endourology 34 ( 2 ) 221 - 225 2021.9

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会

骨盤臓器脱に対する治療として,2010年に経腟メッシュ手術が,2014年に腹腔鏡下仙骨腟固定術が保険収載され,泌尿器科医が骨盤臓器脱に対する治療を行うことも一般的になってきている.2020年4月の診療報酬改定により,新たにロボット支援腹腔鏡下仙骨腟固定術が保険収載された.腹腔鏡下仙骨腟固定術は,正確な剥離操作を要し,深部での縫合結紮操作を多用する手術であることなど,良性疾患に対する手術でありながら手技の難易度が比較的高い術式であると考えられる.これに対して手術支援ロボットを用いることで,手術の難易度が低減されること,手術成績が向上することが期待される.当院でも2020年8月よりロボット支援下仙骨腟固定術を導入した.ロボット支援下仙骨腟固定術のメリットやデメリット,導入の意義などについて,手術導入に向けた取り組みについて述べる.(著者抄録)

Clinical pharmacokinetics of oral azithromycin in epididymal tissue. Reviewed

Sadahira T, Wada K, Ikawa K, Morikawa N, Mitsui M, Araki M, Fujiyoshi M, Ishii A, Watanabe M, Watanabe T, Nasu Y

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 25 ( 10 ) 832 - 834 2019.10

Robotic renal auto transplantation Reviewed

Motoo Araki, Koichiro Wada, Shingo Nishimura, Risa Kubota, Kasumi Kawamura, Yuki Maruyama, Yosuke Mitsui, Takuya Sadahira, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Ayano Ishii, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Nishinihon Journal of Urology 81 ( 3 ) 314 - 320 2019.6

Language：Japanese Publishing type：Research paper (international conference proceedings) Publisher：The West Japan Urological Association

Renal autotransplantation (RAT) is a great surgical procedure for renal preservation, however it is underutilized due to its invasiveness. Robotic RATx has been in use since 2014. We conducted robotic RATx following a feasibility study using a porcine model. A 38-year-old woman with left ureteral stenosis was referred to us for urinary tract reconstruction. She had undergone an emergency Caesarean section for intraperitoneal bleeding secondary to left ovarian rupture four years earlier. After the surgery, she developed hypovolemic shock and disseminated intravascular coagulation (DIC) due to postoperative bleeding. Left internal iliac artery embolization saved her life. However, it resulted in a left ureteral stenosis measuring 2.7 cm that was located 5 cm from the left ureteral orifice, which required chronic ureteral stent exchange. Neither balloon dilation nor laser incision was successful. In addition, retrograde pyelography showed a possible left ureteropelvic junction obstruction. The patient was hesitant about the surgery because of its invasiveness. However, four years later, the patient elected to undergo robotic RATx. To date, only four cases of robotic RATx have been reported, including the current case. The indication of all four cases was extensive ureteral stenosis. Ileal ureter is frequently used for the treatment of extensive ureteral stenosis, but it can entail many problems including urine reabsorption resulting in metabolic acidosis. Ileal ureter is contraindicated for patients with a serum creatinine (sCr) level greater than 2 mg/dl. Even if sCr is less than 2 mg/dl, it is questionable whether sCr will remain less than 2 mg/ dl for the remainder of someone's life. Boari flap can give rise to vesicoureteral reflux causing urinary tract infection. RATx does not have those problems. Robotic RATx is a new, minimally invasive approach to renal preservation.

腎移植、明日への挑戦ロボット自家腎移植

荒木元朗, 和田耕一郎, 西村慎吾, 窪田理沙, 河村香澄, 丸山雄樹, 光井洋介, 定平卓也, 高本篤, 佐古智子, 枝村康平, 小林泰之, 石井亜矢乃, 渡部昌美, 渡邉豊彦, 那須保友

西日本泌尿器科 81 ( 3 ) 314 - 320 2019.6

Language：Japanese Publisher：西日本泌尿器科学会

自家腎移植は本来摘出される腎臓を救済できる優れた手術だが、侵襲が大きく臨床応用の頻度は極めて少ない。2014年以降、傷の小さい低侵襲のロボット自家腎移植が北米を中心に臨床応用されている。当科ではまずブタでfeasibility studyを行いヒトへの臨床応用に移行した。対象は30代女性。左卵巣嚢腫破裂で緊急帝王切開および左付属器切除(出血量4L)。再出血のため左内腸骨動脈の血管塞栓術を施行。術後左尿管口より5cm頭側で長さ2.7cmの尿管狭窄に対し左尿管ステント留置。尿路造影にて左腎盂尿管移行部狭窄も疑われた。4年後、手術目的に当科を紹介されるも躊躇。さらに4年後、再診。創の小さいロボット自家腎移植を選択。傷も小さくステントフリーとなり患者は満足されている。ロボット自家腎移植は我々の症例も含め世界で4例報告されており、すべて距離の長い尿管狭窄に対して行われている。そうした症例に頻用されるileal ureterは腸管の尿の再吸収による代謝性アシドーシスなどが問題となり、Cr>2mg/dlでは禁忌である。Cr>2mg/dlの日本人は56万人も存在し、成人の179人に1人に相当することよりileal ureterを造設したときCr 2mg/dl以下でも、その患者が一生涯Cr 2mg/dl以下で過ごせる可能性は高くない。Boari flapは逆流防止がないもしくは困難で膀胱尿管逆流による尿路感染症などが問題となる。自家腎移植は尿の再吸収による代謝性アシドーシスがなく、逆流防止も可能な優れた手術である。ロボット自家腎移植は腎保存の新しい低侵襲手術である。(著者抄録)

Clitoral Blood Flow Changes after Surgery with Tension-Free Vaginal Mesh for Pelvic Organ Prolapse. Reviewed

Oiwa Y, Watanabe T, Sadahira T, Ishii A, Sako T, Inoue M, Wada K, Kobayashi Y, Araki M, Nasu Y

Acta medica Okayama 73 ( 1 ) 21 - 27 2019.2

THE PROMISING USE OF PROBIOTICS AGAINST RECURRENT URINARY TRACT INFECTIONS

定平卓也, 和田耕一郎, 三井將雄, 石井亜矢乃, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科 80 ( 10 ) 505‐509 - 509 2018.10

Language：Japanese Publisher：西日本泌尿器科学会

尿路感染症に対する治療として中心的な役割を果たしてきた抗菌化学療法は大きな転機を迎えている。世界的な時流として耐性菌の問題や医療経済的にも抗菌薬の使用量を減少させる方向に移行している。尿路感染症においても例外ではなく、そのマネジメントに関して治療法の見直しだけでなく予防の重要性についての議論がなされている。そのうち、これまでに様々な臨床研究において有効性が確認されつつあるプロバイオティクスが抗菌薬とは異なる尿路感染症対策として注目されている。健常な閉経前の女性の腟内においては、基本的に乳酸菌が細菌叢(フローラ)を形成しているが、月経中や閉経後は乳酸菌が減少して腸内細菌が腟内に定着することとなる。その腟がリザーバーとなって細菌を供給し、頻繁に尿路の逆行性感染を引き起こすと考えられている。すなわち、腟内を乳酸菌中心のフローラに保つことで尿路感染症の再発(反復)リスクが低くなることが期待でき、実際にプロバイオティクスを用いた多くの研究が行われている。我々が現在行っている乳酸菌製剤のほか、プロバイオティクスの経口摂取が腟内フローラに与える影響に関しても検証が進んでおり、プロバイオティクスが尿路感染症の予防や治療に寄与することが期待されている。(著者抄録)

THE PROMISING USE OF PROBIOTICS AGAINST RECURRENT URINARY TRACT INFECTIONS Reviewed

定平卓也, 和田耕一郎, 三井將雄, 石井亜矢乃, 荒木元朗, 渡部昌実, 渡邉豊彦, 那須保友

西日本泌尿器科 = The Nishinihon journal of urology 80 ( 10 ) 505 - 509 2018.10

Language：Japanese Publisher：西日本泌尿器科学会

尿路感染症に対する治療として中心的な役割を果たしてきた抗菌化学療法は大きな転機を迎えている。世界的な時流として耐性菌の問題や医療経済的にも抗菌薬の使用量を減少させる方向に移行している。尿路感染症においても例外ではなく、そのマネジメントに関して治療法の見直しだけでなく予防の重要性についての議論がなされている。そのうち、これまでに様々な臨床研究において有効性が確認されつつあるプロバイオティクスが抗菌薬とは異なる尿路感染症対策として注目されている。健常な閉経前の女性の腟内においては、基本的に乳酸菌が細菌叢(フローラ)を形成しているが、月経中や閉経後は乳酸菌が減少して腸内細菌が腟内に定着することとなる。その腟がリザーバーとなって細菌を供給し、頻繁に尿路の逆行性感染を引き起こすと考えられている。すなわち、腟内を乳酸菌中心のフローラに保つことで尿路感染症の再発(反復)リスクが低くなることが期待でき、実際にプロバイオティクスを用いた多くの研究が行われている。我々が現在行っている乳酸菌製剤のほか、プロバイオティクスの経口摂取が腟内フローラに与える影響に関しても検証が進んでおり、プロバイオティクスが尿路感染症の予防や治療に寄与することが期待されている。(著者抄録)

Impact of selective media for detecting fluoroquinolone-insusceptible/extended-spectrum beta-lactamase-producing Escherichia coli before transrectal prostate biopsy

Takuya Sadahira, Koichiro Wada, Motoo Araki, Ayano Ishii, Toyohiko Watanabe, Yoshitsugu Nasu, Masaya Tsugawa, Tadasu Takenaka, Yasutomo Nasu, Hiromi Kumon

INTERNATIONAL JOURNAL OF UROLOGY 24 ( 12 ) 842 - 847 2017.12

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY

ObjectivesTo investigate the prevalence of fluoroquinolone-insusceptible and/or extended-spectrum beta-lactamase-producing Escherichia coli colonizing in the male rectum before transrectal prostate biopsy.
MethodsWe carried out a prospective cohort study of men undergoing transrectal prostate biopsy. CHROMagar Orientation originally supplemented with levofloxacin and CHROMagar Orientation/extended-spectrum beta-lactamase were used for detecting fluoroquinolone-insusceptible and extended-spectrum beta-lactamase-producing Escherichia coli. Rectal specimens were collected before prostate biopsy, and the results of cultures in the selective medium were compared with drug susceptibility measured by standard methods. Targeted prophylactic antimicrobials were administered to patients with drug-resistant Escherichia coli and the incidence of postoperative prostatitis was investigated. In the case of prostatitis, pathogens preoperatively isolated from the rectum and those from urine were compared using pulsed-field gel electrophoresis.
ResultsRectal colonization of fluoroquinolone-insusceptible or extended-spectrum beta-lactamase-producing Escherichia coli was detected in 217 of 694 (31.3%) and 85 of 640 (13.3%) participants, respectively. The sensitivity and specificity of fluoroquinolone-insusceptible selective media were 96.8% and 88.2%, respectively. A total of 618 participants underwent transrectal prostate biopsy, and postoperative acute prostatitis was observed in four of 618 (0.6%) participants. Escherichia coli strains isolated preoperatively from the rectum and postoperatively from urine were found to be identical.
ConclusionsThe present findings showed accuracy and performance of the selective media. Screening cultures before transrectal prostate biopsy using selective media seems to be helpful for guiding antibiotic prophylaxis and thus decreasing the rate of post-biopsy acute prostatitis.

DOI： 10.1111/iju.13447

Antimicrobial susceptibilities of Chlamydia trachomatis isolated from the urethra and pharynx of Japanese males

Seiji Kai, Koichiro Wada, Takuya Sadahira, Motoo Araki, Ayano Ishii, Toyohiko Watanabe, Koichi Monden, Satoshi Uno, Tohru Araki, Yasutomo Nasu

JOURNAL OF INFECTION AND CHEMOTHERAPY 23 ( 8 ) 512 - 516 2017.8

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Objectives: Sexually transmitted infections due to Chlamydia trachomatis (C. trachomatis) are a worldwide public health problem. The aim of this study was to investigate the drug susceptibilities of C. trachomatis strains isolated from the urethra and pharynx of Japanese males.
Methods: Urethral and pharyngeal swabs were collected between 2013 and 2014 from Japanese males with urethritis. Using a McCoy cell line, 18 chlamydial strains were isolated from urethra in 18 patients and 7 from the pharynx in 7 of the 18 patients. The minimum inhibitory concentrations (MICs) of levofloxacin (LVFX) and azithromycin (AZM) were measured using the standard method of the Japanese Society of Chemotherapy.
Results: The MICs of LVFX and AZM against urethral chlamydial strains were 0.125-0.5 mu g/mL and 0.125-0.25 mu g/mL, respectively. In pharyngeal strains, the MICs of LVFX and AZM were 0.125-0.25 mu g/mL and 0.125-0.25 mu g/mL, respectively. In 7 patients with chlamydial strains isolated from both the urethra and pharynx, the MICs of LVFX between these strains were identical in 3 of 6 patients (no growth was observed for one pharyngeal strain), while the MICs of AZM between these strains were identical in all 6 patients (not performed for one patient).
Conclusions: Our data suggest that C. trachomatis strains isolated from the urethra and pharynx of Japanese males are susceptible to LVFX and AZM. Although measuring the MICs of chlamydial strains is labor intensive, it is a significant surveillance tool for treating chlamydial infections and preventing the spread of STIs. (C) 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2017.04.005

Clinical pharmacokinetics of oral levofloxacin and sitafloxacin in epididymal tissue

Takuya Sadahira, Koichiro Wada, Kazuro Ikawa, Norifumi Morikawa, Hiroaki Kurahashi, Takashi Yoshioka, Yuichi Ariyoshi, Yasuyuki Kobayashi, Motoo Araki, Ayano Ishii, Masami Watanabe, Shinya Uehara, Toyohiko Watanabe, Yasutomo Nasu

JOURNAL OF INFECTION AND CHEMOTHERAPY 23 ( 4 ) 214 - 217 2017.4

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Objectives: This study aimed to investigate the penetration of fluoroquinolones into human epididymal tissue.
Methods: The penetration of levofloxacin (LVFX) 500 mg or sitafloxacin (STFX) 100 mg into epididymal tissue was examined. Patients with prostate cancer who were referred for orchiectomy were included. LVFX 500 mg (n = 9) or STFX 100 mg (n = 9) was administered orally 1 h before orchiectomy, and 0.5 g of epididymal tissue and blood samples were collected simultaneously during surgery. Drug concentrations were measured by high-performance liquid chromatography, and patient characteristics and adverse events were analyzed.
Results: The mean ratio of the epididymal concentration to the serum concentration was 1.48 +/- 0.45 for LVFX and 1.54 +/- 0.81 for STFX. For LVFX, the simulated curves estimated the following: maximum concentrations (Cmax) of 8.84 mu g/ml in serum and 14.1 mu g/g in epididymal tissue and area under the concentration-time curve for 24 h (AUC(24)) of 68.5 mu g h/ml in serum and 108.9 mu g h/g in epididymal tissue. For STFX, the Cmax was 1.22 mu g/ml in serum and 1.66 mu g/g in epididymal tissue, and the AUC24 was 9.58 mu g h/ml in serum and 13.1 mu g h/g in epididymal tissue. Neither treatment-related adverse events nor postoperative urogenital infections were observed.
Conclusions: The results of this study suggest that oral administration of LVFX 500 mg or STFX 100 mg achieves effective epididymal concentrations for treatment of epididymitis. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.12.010

Efficacy and safety of 3 day versus 7 day cefditoren pivoxil regimens for acute uncomplicated cystitis: multicentre, randomized, open-label trial

Takuya Sadahira, Koichiro Wada, Motoo Araki, Ayano Ishii, Atsushi Takamoto, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 72 ( 2 ) 529 - 534 2017.2

Language：English Publishing type：Research paper (scientific journal) Publisher：OXFORD UNIV PRESS

Background: Fluoroquinolone-non-susceptible Escherichia coli isolated from patients with acute uncomplicated cystitis are a matter of increasing concern. Cefditoren pivoxil is an oral, beta-lactamase-stable, extended-spectrum cephalosporin that is effective against fluoroquinolone-non-susceptible bacteria.
Objectives: To evaluate the clinical and microbiological efficacies of cefditoren pivoxil against acute uncomplicated cystitis and to determine the optimal duration of cefditoren pivoxil treatment.
Methods: We compared 3 and 7 day regimens of cefditoren pivoxil in a multicentre, randomized, open-label study.
Results: A total of 104 female patients with acute uncomplicated cystitis were enrolled and randomized into 3 day (n = 51) or 7 day (n = 53) treatment groups. At first visit, 94 bacterial strains were isolated from the 104 participants of which 81.7% (85/104) were E. coli. Clinical and microbiological efficacies were evaluated 59 days following administration of the final dose of cefditoren pivoxil. The clinical efficacies of the 3 and 7 day groups were 90.9% (40/44) and 93.2% (41/44), respectively (P = 1.000). The microbiological efficacies of the 3 and 7 day groups were 82.5% (33/40) and 90.2% (37/41), respectively (P = 0.349). There were no adverse events due to cefditoren pivoxil treatment, with the exception of a mild allergic reaction in one patient, after which the cefditoren pivoxil was exchanged for another antimicrobial.
Conclusions: Cefditoren pivoxil is safe and effective for uncomplicated cystitis, with no significant differences in clinical and microbiological efficacies between 3 and 7 day regimens.

DOI： 10.1093/jac/dkw424

Clinical analysis of bacterial strain profiles isolated from urinary tract infections: A 30-year study

Koichiro Wada, Shinya Uehara, Masumi Yamamoto, Takuya Sadahira, Ritsuko Mitsuhata, Motoo Araki, Yasuyuki Kobayashi, Ayano Ishii, Reiko Kariyama, Toyohiko Watanabe, Yasutomo Nasu, Hiromi Kumon

JOURNAL OF INFECTION AND CHEMOTHERAPY 22 ( 7-8 ) 478 - 482 2016.7

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE BV

Objectives: We analyzed bacterial strains isolated from urine samples of patients with urinary tract infections (UTI) at Okayama University Hospital over a 30-year period to characterize trends in species and antimicrobial susceptibilities.
Methods: Clinical isolates were collected from in- and out-patients with pyuria and bacteriuria who were treated between 1984 and 2014 (one episode per patient and plural isolates were counted in poly microbial infection). We examined these isolates to identify pathogens and tested for antimicrobial susceptibility.
Results: Isolates from complicated UTI over a 30-year period revealed Pseudomonas aeruginosa (P. aeruginosa) was the most frequently isolated in the first decade (1984-1994), MRSA in the second decade (1995-2004), and Escherichia coli (E. coli) in the latest decade (2005-2014). In uncomplicated UTI examined over 20 years, E. coli was the most frequently isolated species accounting for 47-94% of isolates. Fluoroquinolone (FQs)-insusceptible E. coli were first isolated in 1994 and increased to about 35% in 2013 in patients with complicated UTI.
Conclusions: Complicated UTI involving P. aeruginosa and MRSA decreased over the last 10 years. Our data suggest that several factors such as shorter hospitalizations, shorter indwelling catheter use, and appropriate antimicrobial use has decreased colonization of P. aeruginosa and MRSA with relative increases in isolation of E. coli including FQs-insusceptible strains. We must continue our surveillance of antimicrobial-resistant bacteria isolated from urine samples and evaluate antibiograms, since their persistence in the urinary tract would be problematic. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.04.004

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