Isavuconazole Treatment for Invasive Fungal Infections in Pediatric Patients

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.

Comparison between EUCAST Broth Microdilution and MIC Strip Test in Defining Isavuconazole In Vitro Susceptibility against Candida and Rare Yeast Clinical Isolates

“…Clinical breakpoints could favour a greater inclusion of isavuconazole in clinical practice, considering that active trials demonstrated its non-inferiority relative to echinocandins for the primary treatment of fungemia and invasive fungal infections [31]. Clinical trials have also been established to test isavuconazole safety against invasive fungal infections among paediatric patients [32]. Moreover, isavuconazole has been compared to voriconazole in invasive aspergillosis, showing high effectiveness [33].…”

Novel Insights into Fungal Infections Prophylaxis and Treatment in Pediatric Patients with Cancer

“…A total of six patients experienced adverse effects during treatment (elevation of transaminases, bilirubin or creatinine), but all were able to complete the treatment [ 110 ]. Zimmerman et al had recently similar results in a cohort of 15 hemato-oncological patients (10 of these later also underwent HSCT) treated with isavuconazole: 9 received the drug as curative treatment, 6 as prophylaxis; no patient showed progressive fungal disease and 6 had complete response at day 90 [ 111 ]. No suspension of chemotherapy or immunosuppression was needed and no drug-to-drug interaction was noted.…”

Clinical research advances of isavuconazole in the treatment of invasive fungal diseases

“…Most of the current studies showed that a daily therapeutic dose of 100 mg was a safe and effective regimen for children with IM weighing less than 30 kg. The first ISA blood concentration monitoring can be performed on the 10th day of ISA treatment and every 2 weeks thereafter (Zimmermann et al, 2022). Similarly, Arrieta et al (2021) evaluated the effects of ISA on the pharmacokinetics, safety and tolerability of 46 immunocompromised children, and the results showed that ISA was well tolerated at 10 mg/kg intravenously or orally, children could achieve plasma concentrations similar to adults.…”

“…Most of the current studies showed that a daily therapeutic dose of 100 mg was a safe and effective regimen for children with IM weighing less than 30 kg. The first ISA blood concentration monitoring can be performed on the 10th day of ISA treatment and every 2 weeks thereafter ( Zimmermann et al., 2022 ). Similarly, Arrieta et al.…”