Scientific validation of prophylactic antimicrobials by measuring their concentration at the site of infection

• Project/Area Number: 18K08630
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Kitasato University
• Principal Investigator: Takayama Yoko 北里大学, 医学部, 教授 (80286278)
• Co-Investigator(Kenkyū-buntansha): 中村 隆俊 獨協医科大学, 医学部, 教授 (10286304) ; 厚田 幸一郎 北里大学, 薬学部, 特任教授 (20306658) ; 花木 秀明 北里大学, 大村智記念研究所, 教授 (60286747)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: cefmetazole / 組織濃度 / 血清濃度 / 下部消化管外科 / 手術部位感染 / CMZ組織内濃度 / CMZ血清濃度 / CMZ血中濃度 / 消化器外科 / CMZ / 血中濃度 / 組織内濃度 / 腎機能低下 / 周術期予防抗菌薬 / 抗菌薬適正使用

Outline of Final Research Achievements

This prospective cohort study was performed at a single tertiary care center. The data of 105 patients who underwent colorectal surgery between October 2017 and September 2019 were evaluated. The primary outcome was the incidence of surgical site infections (SSIs). Univariate analysis was performed to investigate the association between SSIs, perioperative factors, and the serum and tissue concentrations of cefmetazole (CMZ). In univariate analysis with P≦0.10, cefmetazole concentration in subcutaneous fat tissue at skin closure was found to be a significant risk factor for surgical site infections. Age, additional intraoperative administration of cefmetazole, and creatinine clearance were also significant risk factors for the occurrence of SSIs.
Low subcutaneous fat CMZ concentrations at skin closure during gastrointestinal operations may also be involved in the occurrence of SSIs.

Academic Significance and Societal Importance of the Research Achievements

これまでに、周術期予防抗菌薬の有効性を血清濃度から検討する研究は報告されてきた。しかし、感染が起きる局所組織の抗菌薬濃度が直に測定された大規模研究データは存在せず、血清濃度から局所感染の有効性が類推されてきた。本研究を通じて、下部消化管手術症例において、血清ならびに皮下・患部周辺組織の抗菌薬濃度を経時的に測定し皮膚閉創時の低い皮下脂肪組織CMZ濃度がSSIsの発生に関与する可能性を見出した。組織濃度とSSIsを科学的に検証できたことは、極めて意義深い。
今後、抗菌薬適正使用の推進、不必要な医療費の削減、および薬剤耐性菌の抑制に繋がることが期待される。

Research Products

• [Journal Article] Timing of re-dosing based on population pharmacokinetic-pharmacodynamics target attainment analysis of cefmetazole in subjects undergoing lower gastrointestinal surgery. (2022)
  • Author(s): Komatsu T, Morita H, Takayama Y, Natsume Y, Tomoda Y, Miura H, Sato T, Nakamura T, Toda M, Okamoto H, Hanaki H, Atsuda K
  • Journal Title: Journal of Infection and Chemotherapy Volume: 28 Issue: 8 Pages: 1105-1111
  • DOI: 10.1016/j.jiac.2022.03.024
  • Peer Reviewed / Open Access
• [Journal Article] Association of serum and fat tissue antibiotic concentrations with surgical site infections in lower gastrointestinal surgery (2022)
  • Author(s): Takayama Y, Komatsu T, Nakamura T, Tomoda Y, Toda M, Miura H, Sato T, Atsuda K, Okamoto H, Hanaki H.
  • Journal Title: Surgery Volume: 171 Issue: 4 Pages: 1000-1005
  • DOI: 10.1016/j.surg.2021.10.013
  • Peer Reviewed / Open Access
• [Presentation] 下部消化管手術におけるSSI発生リスクと血清および組織CMZ濃度の関連性 (2022)
  • Author(s): 高山陽子
  • Organizer: 第96回日本感染症学会総会・学術講演会
• [Presentation] 下部消化管手術における周術期予防抗菌薬の血中および組織内濃度の関係性 (2020)
  • Author(s): 高山陽子
  • Organizer: 第68回 日本化学療法学会総会
• [Presentation] 周術期予防抗菌薬の適正化への取り組み (2019)
  • Author(s): 高山陽子
  • Organizer: 第67回 日本化学療法学会総会
  • Invited