Isavuconazole Treatment for Invasive Fungal Infections in Pediatric Patients

被引:11
作者
Zimmermann, Philippe [1 ]
Brethon, Benoit [2 ]
Roupret-Serzec, Julie [1 ]
Caseris, Marion [3 ]
Goldwirt, Lauriane [4 ,5 ]
Baruchel, Andre [2 ]
de Tersant, Marie [2 ]
机构
[1] Univ Robert Debre Hosp, AP HP, Dept Pharm, F-75019 Paris, France
[2] Univ Robert Debre Hosp, AP HP, Dept Pediat Hematoimmunol, F-75019 Paris, France
[3] Univ Robert Debre Hosp, AP HP, Dept Gen Paediat, F-75019 Paris, France
[4] Univ Paris, St Louis Hosp, AP HP, Pharmacol Dept, F-75010 Paris, France
[5] Univ Paris Diderot, Fac Med, Sorbonne Paris Cite, UMRS976, F-75010 Paris, France
关键词
pediatric; isavuconazole; invasive fungal infection; PHARMACODYNAMICS; PHARMACOKINETICS; VORICONAZOLE; ANTIFUNGALS; CHILDREN; THERAPY; SAFETY;
D O I
10.3390/ph15030375
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
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