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卡泊芬净的杀菌活性及药代动力学/药效学,作为指导耐氟康唑近平滑念珠菌血症抗真菌治疗的工具

Fungicidal activity and PK/PD of caspofungin as tools to guide antifungal therapy in a fluconazole-resistant C. parapsilosis candidemia.

作者信息

Tascini Carlo, Sozio Emanuela, Di Paolo Antonello, Tintori Giancarlo, Leonildi Alessandro, Bertolino Giacomo, Carmassi Franco, Tagliaferri Enrico, Menichetti Francesco, Barchiesi Francesco

机构信息

a First Infectious Diseases Unit , Ospedale Cotugno, Azienda Ospedaliera dei Colli , Napoli , Italy.

b Emergency Medicine Unit , Azienda Ospedaliera Universitaria Pisana , Pisa , Italy.

出版信息

J Chemother. 2017 Dec;29(6):376-379. doi: 10.1080/1120009X.2017.1289308. Epub 2017 Feb 15.

Abstract

Candida parapsilosis may be responsible for bloodstream infections (BSI) and it is characterised by an increased incidence of fluconazole resistance. A 75-year old woman with severe comorbidities received the insertion of a peripherally inserted central venous catheter. Fluconazole did not prevent a C. parapsilosis BSI hence caspofungin was started after a nephrotoxic first-line treatment with amphotericin B. The ratio of peak plasma concentration over the minimum inhibitory concentration (C/MIC) was adopted to maximise efficacy of caspofungin. MIC and plasma C values were obtained by broth microdilution and LC-MS, respectively. Interestingly, daily doses of 1 mg/kg (total daily dose, 50 mg) allowed the achievement of C/MIC values > 10. The optimised regimen was safe and effective, leading to negative blood culture at day 8. The patient was discharged home at day 21. Therefore, individualised dosing regimens of caspofungin may be effective and safe even in the case of C. parapsilosis BSI.

摘要

近平滑念珠菌可能导致血流感染(BSI),其特征是氟康唑耐药性发生率增加。一名患有严重合并症的75岁女性接受了外周静脉穿刺中心静脉导管置入术。氟康唑未能预防近平滑念珠菌血流感染,因此在使用具有肾毒性的一线治疗药物两性霉素B后,开始使用卡泊芬净。采用血浆峰浓度与最低抑菌浓度之比(C/MIC)来最大化卡泊芬净的疗效。MIC和血浆C值分别通过肉汤微量稀释法和液相色谱-质谱法获得。有趣的是,每日剂量为1mg/kg(每日总剂量50mg)可使C/MIC值>10。优化后的治疗方案安全有效,在第8天血培养转阴。患者在第21天出院。因此,即使在近平滑念珠菌血流感染的情况下,卡泊芬净的个体化给药方案也可能是安全有效的。

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