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艾沙康唑治疗儿童侵袭性真菌感染

Isavuconazole Treatment for Invasive Fungal Infections in Pediatric Patients.

作者信息

Zimmermann Philippe, Brethon Benoit, Roupret-Serzec Julie, Caseris Marion, Goldwirt Lauriane, Baruchel André, de Tersant Marie

机构信息

Department of Pharmacy, University Robert Debre Hospital, AP-HP, 75019 Paris, France.

Department of Pediatric Hemato-Immunology, University Robert Debre Hospital, AP-HP, 75019 Paris, France.

出版信息

Pharmaceuticals (Basel). 2022 Mar 19;15(3):375. doi: 10.3390/ph15030375.

Abstract

This work’s objective was to evaluate the safety of isavuconazole (ISA) as a treatment or prophylaxis for invasive fungal infections (IFIs) in immunocompromised children. IFI was reported as proven or probable according to international definitions. Therapeutic drug monitoring was performed using mass tandem spectrometry to quantify trough plasma concentrations. Targeted ISA levels were 2−4 mg/L, as reported in adult series. Nine patients received ISA as a curative treatment, and six received ISA as prophylaxis. IFIs were proven in four cases and probable in five. The median ISA trough plasma concentration in curative use was 3.19 mg/L [0.88;5.00], and it was 2.94 mg/L [2.77;3.29] in the prophylactic use. The median durations of treatment were 81 days [15;276] and 95 days [15;253], respectively. Three patients had elevated aspartate aminotransferase and alanine aminotransferase, and three patients had elevated creatinine serum. The IFI response was satisfactory in all cases at day 90. No side effects were reported. No patients developed an IFI. Our data underline the safety of an ISA 100 mg dosing regimen in children of <30 kg, which we recommend in this fragile population. We suggest that ISA plasma levels are monitored 10 days after ISA initiation and then every two weeks, alongside guided therapeutic drug monitoring (TDM) administration.

摘要

这项研究的目的是评估艾沙康唑(ISA)作为免疫功能低下儿童侵袭性真菌感染(IFI)治疗或预防药物的安全性。根据国际定义,IFI被报告为确诊或疑似。采用串联质谱法进行治疗药物监测,以定量测定血浆谷浓度。如成人系列报道,ISA的目标水平为2−4mg/L。9例患者接受ISA进行治疗,6例接受ISA进行预防。4例确诊为IFI,5例疑似IFI。治疗时ISA血浆谷浓度中位数为3.19mg/L[0.88;5.00],预防时为2.94mg/L[2.77;3.29]。治疗持续时间中位数分别为81天[15;276]和95天[15;253]。3例患者天门冬氨酸氨基转移酶和丙氨酸氨基转移酶升高,3例患者血清肌酐升高。在第90天所有病例的IFI反应均令人满意。未报告有副作用。无患者发生IFI。我们的数据强调了100mg ISA给药方案在体重<30kg儿童中的安全性,我们建议在这一脆弱人群中使用该方案。我们建议在开始使用ISA后10天监测ISA血浆水平,然后每两周监测一次,并同时进行指导性治疗药物监测(TDM)给药。

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