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KAKEN_18K06795seika.pdf
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:232.2 KB
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:May 17, 2022 |
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Total downloads since May 17, 2022 : 419
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耐性菌感染症の克服を目指した抗菌薬個別最適化投与法の構築
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タイセイキン カンセンショウ ノ コクフク オ メザシタ コウキンヤク コベツ サイテキカ トウヨホウ ノ コウチク
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Taiseikin kansenshō no kokufuku o mezashita kōkin'yaku kobetsu saitekika tōyohō no kōchiku
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Development of individually optimized dosing regimen for antimicrobial agents aiming at overcoming antimicrobial-resistant bacterial infections
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松元, 一明
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マツモト, カズアキ
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Matsumoto, Kazuaki
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慶應義塾大学・薬学部 (芝共立) ・教授
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Research team head
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科研費研究者番号 : 60733160
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2021
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科学研究費補助金研究成果報告書
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2020
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フロモキセフとラタモキセフは基質特異性拡張型β-ラクタマーゼ（ESBL）産生大腸菌に抗菌活性を示すため注目されているが、PK/PD解析が実施されておらず臨床応用に至っていない。そこで、ESBL産生大腸菌に対するフロモキセフとラタモキセフのPK/PDパラメータを明らかにすることを目的として研究を行った。In vitro試験で、両剤共に時間依存的な抗菌活性を示した。好中球減少大腿部感染マウスモデルを用いてPK/PD解析を実施した結果、time above MICに最も相関することが示され、最大殺菌効果である1 log10 killを達成するための目標値はそれぞれ35.1%と69.6%であった。
Although flomoxef and cefmetazole has attracted substantial attention as an antibiotic against extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-producing E. coli), the pharmacokinetics/pharmacodynamics (PK/PD) characteristics of flomoxef and cefmetazole against ESBL-producing E. coli is unclear. The aim of this study was to determine the PK/PD index of flomoxef and cefmetazole against ESBL-producing E. coli. Time-kill curves exhibited time-dependent activities. In neutropenic murine thigh infection experiments, the antibacterial activities of flomoxef and cefmetazole correlated with the time that the free drug concentration remaining above the minimum inhibitory concentration (MIC) (fT>MIC) The target values of fT>MIC for 1 log10 kill reduction were 35.1% for flomoxef and 69.6% for cefmetazole. Thus, fT>MIC is the most significant PK/PD index of flomoxef and cefmetazole against ESBL-producing E. coli and its target values are ≧40% and 70%, respectively.
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研究種目 : 基盤研究 (C) (一般)
研究期間 : 2018～2020
課題番号 : 18K06795
研究分野 : 医療薬学
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