Relationship between PK/PD of Cefepime and Clinical Outcome in Febrile Neutropenic Patients with Normal Renal Function

Yamashita Yoshiko, Kamiyama Hidekazu, Yamamoto Asuka, Kanoh Hiroki, Yuhki Yoshimitsu, Ueda Akira, Kawamoto Yukari, Gotoh Yoshikazu, Yamamoto Satoshi

doi:10.1248/yakushi.16-00168

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腎機能正常発熱性好中球減少症患者に対するセフェピム至適投与法の検討<br/>—PK/PDと臨床的アウトカムの関連性から—
腎機能正常発熱性好中球減少症患者に対するセフェピム至適投与法の検討 : PK/PDと臨床的アウトカムの関連性から
ジンキノウセイジョウハツネツセイコウチュウキュウゲンショウショウカンジャニタイスルセフェピムシテキトウヨホウノケントウ : PK/PD トリンショウテキアウトカムノカンレンセイカラ

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The efficacy of cefepime (CFPM) is known to depend on the ratio of the time that the serum levels exceed the minimum inhibitory concentration (MIC) to the dosing interval (%T>MIC). The objective of this study was to clarify the relation between %T>MIC and clinical outcome of CFPM, and to identify the optimal dosage regimen. We investigated the outcome of CFPM treatment for febrile neutropenia (FN) patients with normal renal function. Treatment success was defined as the completion of FN therapy with CFPM only. And we calculated %T>MIC for each case based on population pharmacokinetic parameters. The MIC value for simulation was set as 8 μg/mL. In logistic regression analysis, treatment success was significantly associated with the elevation of %T>MIC in the group with persistent neutropenia, yielding a receiver operating characteristic curve with an optimal cutoff value of 73.1%. Next, we simulated %T>MIC for each case under various dosing regimens. For patients whose creatinine clearance (CLcr) exceeded 100 mL/min, it was found to be difficult to attain the objective under the current regimen. In contrast, it was calculated that treatment with 2 g three times a day (t.i.d.) could attain the objective for most of the patients with 3 h of infusion. These results suggest that CFPM treatment under the current regimen is ineffective for FN patients with normal or augmented renal function, and that 2 g t.i.d. is necessary in quite a lot cases, although such use is off-label.<br>

Journal

YAKUGAKU ZASSHI

YAKUGAKU ZASSHI 136 (12), 1641-1649, 2016

The Pharmaceutical Society of Japan

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