Optimization of antimicrobial therapy based on relation and interaction among drug, causative organism and host immunity

• Project/Area Number: 15K08590
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Hiroshima University
• Principal Investigator: Ikawa Kazuro 広島大学, 医歯薬保健学研究科(薬), 准教授 (40363048)
• Co-Investigator(Kenkyū-buntansha): 森川 則文 広島大学, 医歯薬保健学研究科(薬), 教授 (30346481) ; 大毛 宏喜 広島大学, 病院(医), 教授 (70379874)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed(Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost : ¥3,700,000、Indirect Cost : ¥1,110,000); Fiscal Year 2017 : ¥1,040,000 (Direct Cost : ¥800,000、Indirect Cost : ¥240,000); Fiscal Year 2016 : ¥1,300,000 (Direct Cost : ¥1,000,000、Indirect Cost : ¥300,000); Fiscal Year 2015 : ¥2,470,000 (Direct Cost : ¥1,900,000、Indirect Cost : ¥570,000)
• Keywords: 臨床 / 感染症 / 薬物動態 / 薬力学

Outline of Final Research Achievements

This research project aimed to elucidate relation and interaction among drug, causative organism and host immunity, in order to optimize antimicrobial therapy. The research monitored concentrations of drugs, such as beta-lactams, quinolones, aminoglycosides, anti-resistant bacteria, and antifungals, in plasma, peritoneal fluid, peritoneum, prostate and epididymis tissues. Being combed with various minimum inhibitory concentration, pharmacodynamic time-killing and clinical data, these pharmacokinetic data were used for population modeling and simulation. Based on the relation and interaction among drug, organism and host, computer tools were created, applied to patients for optimizing antimicrobial therapy, and assessed with their feedback information.

Research Products

• [Journal Article] Population pharmacokinetics/pharmacodynamics of linezolid in sepsis patients with and without continuous renal replacement therapy. (2018)
  • Author(s): Ide Takeshi, Takesue Yoshio, Ikawa Kazuro, Morikawa Norifumi, Ueda Takashi, Takahashi Yoshiko, Nakajima Kazuhiko, Takeda Kenta, Nishi Shinichi.
  • Journal Title: Int J Antimicrob Agents. Volume : in press
  • DOI: 10.1016/j.ijantimicag.2018.01.021
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and outcome of tazobactam/piperacillin in Japanese patients undergoing low-flow continuous renal replacement therapy: dosage considerations. (2017)
  • Author(s): Kohama Hanako, Ide Takeshi, Ikawa Kazuro, Morikawa Norifumi, Nishi Shinichi.
  • Journal Title: Clin Pharmacol. Volume : Volume 9 Pages : 39-44
  • DOI: 10.2147/cpaa.s127502
  • Peer Reviewed
• [Journal Article] Clinical pharmacokinetics of oral levofloxacin and sitafloxacin in epididymal tissue. (2017)
  • Author(s): Sadahira Takuya, Wada Koichiro, Ikawa Kazuro, Morikawa Norifumi, Kurahashi Hiroaki, Yoshioka Takashi, Ariyoshi Yuichi, Kobayashi Yasuyuki, Araki Motoo, Ishii Ayano, Watanabe Masami, Uehara Shinya, Watanabe Toyohiko, Nasu Yasutomo.
  • Journal Title: J Infect Chemother. Volume : 23 Pages : 214-217
  • DOI: 10.1016/j.jiac.2016.12.010
  • Peer Reviewed
• [Journal Article] Pharmacokinetics of piperacillin-tazobactam in plasma, peritoneal fluid and peritoneum of surgery patients, and dosing considerations based on site-specific pharmacodynamic target attainment. (2017)
  • Author(s): Murao Naoki, Ohge Hiroki, Ikawa Kazuro, Watadani Yusuke, Uegami Shinnosuke, Shigemoto Norifumi, Shimada Norimitsu, Yano Raita, Kajihara Toshiki, Uemura Kenichiro, Murakami Yoshiaki, Morikawa Norifumi, Sueda Taijiro.
  • Journal Title: Int J Antimicrob Agents. Volume : 50 Pages : 393-398
  • DOI: 10.1016/j.ijantimicag.2017.03.025
  • Peer Reviewed
• [Journal Article] Clinical pharmacokinetics and pharmacodynamic target attainment of pazufloxacin in prostate tissue: Dosing considerations for prostatitis. (2017)
  • Author(s): Nakamura Kogenta, Ikawa Kazuro, Nishikawa Genya, Kobayashi Ikuo, Narushima Masahiro, Muramatsu Hiroyuki, Morinaga Shingo, Kajikawa Keishi, Kato Yoshiharu, Watanabe Masahito, Zennami Kenji, Kanao Kent, Morikawa Norifumi, Sumitomo Makoto.
  • Journal Title: J Infect Chemother. Volume : 23 Pages : 809-813
  • DOI: 10.1016/j.jiac.2017.08.005
  • Peer Reviewed
• [Journal Article] Pharmacokinetic/pharmacodynamic analysis of teicoplanin in patients with MRSA infections. (2016)
  • Author(s): Matsumoto K, Watanabe E, Kanazawa N, Fukamizu T, Shigemi A, Yokoyama Y, Ikawa K, Morikawa N, Takeda Y.
  • Journal Title: The Journal of Clinical Pharmacology Volume : 8 Pages : 15-18
  • DOI: 10.2147/cpaa.s96143
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The pharmacokinetics of ampicillin-sulbactam in anuric patients: dosing optimization for prophylaxis during cardiovascular surgery. (2016)
  • Author(s): Yokoyama Y, Matsumoto K, Ikawa K, Watanabe E, Yamamoto H, Imoto Y, Morikawa N, Takeda Y.
  • Journal Title: International Journal of Clinical Pharmacology Volume : 1 Pages : 1-5
  • DOI: 10.1007/s11096-016-0286-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Therapeutic drug monitoring of voriconazole in Japanese patients: analysis based on clinical practice data. (2016)
  • Author(s): Matsumoto K, Abematsu K, Shigemi A, Kanazawa N, Watanabe E, Yokoyama Y, Ikawa K, Morikawa N, Takeda Y.
  • Journal Title: J Chemother. Volume : 28 Pages : 198-202
  • DOI: 10.1179/1973947815y.0000000057
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CYP2C19遺伝子多型と代謝物濃度をふまえたTDMによるボリコナゾール投与量適正化が有用であった2例. (2016)
  • Author(s): 茂見茜里, 松元一明, 渡辺英里香, 猪川和朗, 金澤直子, 横山雄太, 梅﨑靖弘, 池田龍二, 森川則文, 武田泰生.
  • Journal Title: 日外感染症会誌 Volume : 13 Pages : 661-667
  • Peer Reviewed
• [Journal Article] Population pharmacokinetic-pharmacodynamic target attainment analysis of sulbactam in patients with impaired renal function: dosing considerations for Acinetobacter baumannii infections. (2015)
  • Author(s): Yokoyama Y, Matsumoto K, Ikawa K, Watanabe E, Morikawa N, Takeda Y.
  • Journal Title: J. Infect. Chemother. Volume : 21 Pages : 284-289
  • DOI: 10.1016/j.jiac.2014.12.005
  • Peer Reviewed / Open Access
• [Journal Article] Penetration of piperacillin-tazobactam into human prostate tissue and dosing considerations for prostatitis based on site-specific pharmacokinetics and pharmacodynamics. (2015)
  • Author(s): Kobayashi I, Ikawa K, Nakamura K, Nishikawa G, Kajikawa K, Yoshizawa T, Watanabe M, Kato Y, Zennami K, Kanao K, Tobiume M, Yamada Y, Mitsui K, Narushima M, Morikawa N, Sumitomo M.
  • Journal Title: J. Infect. Chemother. Volume : 21 Pages : 575-580
  • DOI: 10.1016/j.jiac.2015.04.015
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Risk Factors for Ganciclovir-Induced Thrombocytopenia and Leukopenia (2015)
  • Author(s): Matsumoto K, Shigemi A, Ikawa K, Kanazawa N, Fujisaki Y, Morikawa N, Takeda Y.
  • Journal Title: Biol. Pharm. Bull. Volume : 38 Issue : 2 Pages : 235-238
  • DOI: 10.1248/bpb.b14-00588
  • Peer Reviewed / Open Access
• [Journal Article] 抗真菌薬・抗ウイルス薬の臨床薬物動態／薬力学の解明とこれに基づく最適治療法の構築. (2015)
  • Author(s): 猪川和朗, 松元一明, 武田泰生, 森川則文.
  • Journal Title: 臨床薬理の進歩 Volume : 36 Pages : 72-80
  • Acknowledgement Compliant
• [Presentation] Population pharmacokinetic-pharmacodynamic modeling and simulation of imipenem for dosing optimization in pediatric patients. (2017)
  • Author(s): Ikawa K, Morikawa N.
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Int'l Joint Research
• [Presentation] Prediction of thrombocytopenia associated with linezolid based on pharmacokinetic-pharmacodynamic simulation. (2017)
  • Author(s): Onita T, Ishihara N, Nishimura N, Tamaki H, Ikawa K, Morikawa N, Naora K.
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Int'l Joint Research
• [Presentation] Population pharmacokinetic analysis of piperacillin and tazobactam by using their blood and urine level data in Japanese pediatric patients. (2017)
  • Author(s): Ishihara N, Nishimura N, Ikawa K, Tamaki H, Morikawa N, Naora K.
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Int'l Joint Research
• [Presentation] Voriconazole TDM based on both unchanged drug and metabolite concentrations in Japanese patients. (2017)
  • Author(s): Shigemi A, Watanabe E, Umezaki Y, Ikeda R, Matsumoto K, Yokoyama Y, Ikawa K, Morikawa N, Takeda Y.
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Int'l Joint Research
• [Presentation] External evaluation of amikacin population pharmacokinetic models in Japanese adult patients. (2017)
  • Author(s): Sako K, Yoshikawa N, Hashimoto N, Matsuki Y, Arai K, Ikawa K, Morikawa N, Matsuda Y.
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Int'l Joint Research
• [Presentation] Estimation of the duration to reach peak arbekacin concentration by Monte Carlo simulation. (2017)
  • Author(s): Yamaguchi K, Abe T, Takeuchi T, Watanabe M, Tsuchiya K, Ikawa K, Fukuoka N, Kaji M, Tanaka H, Asakura M, Kosaka S, Houchi H.
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Int'l Joint Research
• [Presentation] Pharmacokinetic and pharmacodynamic characterization of piperacillin-tazobactam, flomoxef and pazufloxacin in prostate tissue and plasma of prostatic hypertrophy patients. (2017)
  • Author(s): Kuroda A, Ikawa K, Ugawa H, Tanaka K, Odagawa S, Matsuyama Y, Nakamura K, Nishikawa G, Kobayashi I, Sumitomo M, Morikawa N.
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Int'l Joint Research
• [Presentation] Pharmacokinetic/pharmacodynamic evaluation of teicoplanin against Staphylococcus aureus in murine thigh infection model. (2017)
  • Author(s): Takeda Y, Watanabe E, Shigemi A, Umezaki Y, Nakamura K, Ueno K, Ikeda R, Yokoyama Y, Matsumoto K, Ikawa K, Morikawa N.
  • Organizer: 15th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology
  • Int'l Joint Research
• [Presentation] Semi-mechanistic pharmacokinetic/pharmacodynamic modeling and simulation for time-kill curve profile of sulbactam against Acinetobacter baumannii. (2017)
  • Author(s): Yokoyama Y, Ikawa K, Matsumoto K, Nakamura T, Morikawa N.
  • Organizer: 第11回次世代を担う若手医療薬科学シンポジウム
• [Presentation] セフェピム投与後に代謝性脳症を発現し薬物血中濃度を測定した1例. (2017)
  • Author(s): 眞継賢一, 猪川和朗, 森川則文, 濱口良彦.
  • Organizer: 第65回日本化学療法学会学術集会・第91回日本感染症学会学術講演会
• [Presentation] Ampicillin-sulbactamのヒト前立腺組織移行性の検討. (2016)
  • Author(s): 田中敬樹, 猪川和朗, 右川博明, 黒田明, 中村小源太, 西川源也, 小林郁生, 住友誠, 森川則文.
  • Organizer: 第37回日本臨床薬理学会年会
  • Place of Presentation: 米子市，鳥取県
  • Year and Date: 2016-12-01
• [Presentation] βラクタマーゼ阻害剤配合抗菌剤の投与設計～高齢患者でのESBL産生菌感染症に対するPIPC/TAZ至適投与法の検討～. (2016)
  • Author(s): 石原慎之, 西村信弘, 猪川和朗, 玉木宏樹, 狩野芙美, 三浦聖高, 礒部威, 森川則文, 直良浩司.
  • Organizer: 第26回日本医療薬学会年会
  • Place of Presentation: 京都市，京都府
  • Year and Date: 2016-09-17
• [Presentation] Intraperitoneal penetration of piperacillin-tazobactam in patients undergoing abdominal surgery. (2016)
  • Author(s): Ohge H, Murao N, Ikawa K, Watadani Y, Uegami S, Shigemoto N, Shimada N, Kajihara T, Yano R, Morikawa N, Sueda T.
  • Organizer: 56th Interscience Conference on Antimicrobial Agents and Chemotherapy & 116th General Meeting of the American Society for Microbiology
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-06-16
  • Int'l Joint Research
• [Presentation] Pharmacokinetics of daptomycin (DAP) in patients undergoing continuous veno-venous hemodiafiltration (CVVHDF). (2016)
  • Author(s): Ide T, Nishi S, Takesue Y, Ikawa K, Morikawa N.
  • Organizer: 56th Interscience Conference on Antimicrobial Agents and Chemotherapy & 116th General Meeting of the American Society for Microbiology
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-06-16
  • Int'l Joint Research
• [Presentation] 高齢肺炎患者におけるPIPC/TAZの腎毒性発現と薬物動態の関連性. (2016)
  • Author(s): 西村信弘, 狩野芙美, 石原慎之, 礒部威, 猪川和朗, 森川則文, 直良浩司.
  • Organizer: 第64回日本化学療法学会総会
  • Place of Presentation: 神戸市，兵庫県
  • Year and Date: 2016-06-09
• [Presentation] ガンシクロビル誘発性の血小板減少および白血球減少のリスク因子解析. (2016)
  • Author(s): 茂見茜里, 松元一明, 猪川和朗, 森川則文, 武田泰生.
  • Organizer: 第64回日本化学療法学会総会
  • Place of Presentation: 神戸市，兵庫県
  • Year and Date: 2016-06-09
• [Presentation] PIPC/TAZの母集団PK-PDモデリングに基づく75歳以上肺炎患者への個別最適化投与. (2016)
  • Author(s): 石原慎之, 西村信弘, 猪川和朗, 玉木宏樹, 狩野芙美, 三浦聖高, 礒部威, 森川則文, 直良浩司.
  • Organizer: 第33回日本TDM学会学術大会
  • Place of Presentation: 宇都宮市，栃木県
  • Year and Date: 2016-05-28
• [Presentation] Clinical efficacy, safety and population pharmacokinetics of piperacillin/tazobactam in late-elderly patients with nursing and healthcare-associated pneumonia. (2015)
  • Author(s): Nishimura N, Ishihara N, Karino F, Moriyama H, Miura K, Okimoto T, Tsubata Y, Hamaguchi S, Kuraki T, Ikawa K, Morikawa N, Isobe T, Naora K.
  • Organizer: Annual Meeting and Exposition of American Association of Pharmaceutical Scientists
  • Place of Presentation: Orlando, USA
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] 薬剤耐性緑膿菌に対するコリスチン単剤・併用投与法のPK-PD検討. (2015)
  • Author(s): 横山雄太, 猪川和朗, 長岡里枝, 小野寺一, 木場由美子, 原稔典, 横崎典哉, 大毛宏喜, 森川則文.
  • Organizer: 第63回日本化学療法学会西日本支部総会・第85回日本感染症学会西日本地方会学術集会・第58回日本感染症学会中日本地方会学術集会
  • Place of Presentation: 奈良
  • Year and Date: 2015-10-15
• [Presentation] メロペネムの膵液への移行に関する薬物動態とグラム陰性桿菌に対する至適投与法の検討. (2015)
  • Author(s): 近藤成, 猪川和朗, 村上義昭, 上村健一郎, 橋本泰司, 中川直哉, 佐々木勇人, 大毛宏喜, 森川則文, 末田泰二郎.
  • Organizer: 第46回日本膵臓学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-06-19
• [Presentation] 精巣・精巣上体組織への薬物移行性の検討～各種抗菌薬の比較～. (2015)
  • Author(s): 定平卓也, 和田耕一郎, 山本満寿美, 光畑律子, 石井亜矢乃, 狩山玲子, 渡辺豊彦, 猪川和朗, 森川則文, 公文裕巳.
  • Organizer: 第63回日本化学療法学会総会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-04