gms | German Medical Science

Introduction: Low voriconazole plasma levels have been linked to therapeutic failure in children. A significant pharmacodynamic association between a voriconazole trough plasma concentration <1mg/L and survival has been reported. However, up to 44% of children receiving voriconazole would fail to achieve plasma trough concentrations above 1 mg/L. We performed a prospective analysis on trough serum concentrations of voriconazol and investigated if these levels could be associated with the outcome of IFI.

Material and methods: We performed a retrospective analysis to determine the percentage of inadequate trough concentrations in children and adolescent diagnosed with invasive fungal infection (proven and probable IFI) admitted at Institute of Pediatric Oncology between May, 2012 and December, 2013; receiving the current recommended dosing regimen of voriconazole.

Results: A total of 29 voriconazole plasma trough measurements from 11 patients (median age 10 years) obtained during voriconazole therapy were analysed; being 7 females and 7 caucasians. Among the 11 patients treated with voriconazole, 7 had proven and 4 probable IFI; 13/25 were neutropenic at the time of diagnosis. At day 5 after the start of voriconazole therapy, the voriconazole trough serum concentration was measured by high-performance liquid chromatography. Overall, in 9 patients, the first trough concentration measured after initiation of voriconazole treatment was below the target concentration of 1 mg/L. In all of them, treatment was adjusted after voriconazole concentration measurement, and 3 resulted in trough concentration between 1 and 5 mg/L. In the remaining 6 patients (3 proven and 3 probable IFI), multiple interventions had resulted in no target attainment and one patient died. All of two patients who had achieved the target concentration in the first trough concentration measured after initiation of voriconazole treatment had complete response (CR). The 30 days all -cause crude mortality rate was 36% and a significant relationship with voriconazole therapeutic plasma levels was not demonstrated (p=0.14). 75% of these deaths were due to the IFI per se.

Conclusion: Our study indicates that adequate exposure defined as a trough concentration of 1 mg/L was not achieved in 54% of patients. A significant relationship between voriconazole therapeutic plasma levels and mortality was not demonstrated. Interestingly, 5 of 6 patients diagnosed with proven and probable IFI did not attain the target concentration and had complete response.