2020 Fiscal Year Final Research Report
Development of individually optimized dosing regimen for antimicrobial agents aiming at overcoming antimicrobial-resistant bacterial infections
Project/Area Number |
18K06795
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 47060:Clinical pharmacy-related
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Research Institution | Keio University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Keywords | ESBL産生大腸菌 / フロモキセフ / セフメタゾール / PK/PD |
Outline of Final Research Achievements |
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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Free Research Field |
医療薬学
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Academic Significance and Societal Importance of the Research Achievements |
近年、世界的に増加しているESBL産生菌に対して、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、科学的根拠をもって新たな治療法を確立した本研究の社会的意義は大きい。今後、カルバペネム系薬に代わる治療薬として臨床応用が期待される。学術的意義として、これまでセフェム系薬の目標PK/PDパラメータ値は一括りにされていたが、オキサセフェム系薬、セファマイシン系薬で異なることが明らかとなった。本研究より、抗菌薬により目標PK/PDパラメータ値が異なる可能性が示され、治療最適化のためには各薬物の特性を基礎研究でさらに検証する必要があると考えられた。
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