Neues aus der Welt der Antimykotika

The past two decades have seen a considerable increase in both number and overall relevance of invasive fungal infections in pediatric hospitals. At the same time, however, improved microbiological and imaging techniques and an increased awareness among physicians have shifted the diagnosis from the autopsy to the bedside. Major advances have been made in the definition of fungal diseases, the algorithms of antifungal interventions, the design and implementation of clinical trials and the development of standardized in vitro susceptibility testing. Most importantly, a number of new antifungal agents has entered the clinical arena with the general perception that antifungal therapy has become safer, more effective, but also more complicated. With the exception of amphotericin B products, there are important differences in distribution and clearance in pediatric patients relative to adults. In 23 to 40 week gestation infants, recent population PK-analyses have demonstrated that dosing will require adjustment to BGA and PNA to achieve targeted systemic exposure. Preliminary pharmacokinetic data obtained for echinocandin agents suggest a lower dosage for caspofungin (25mg/msqu QD), while bridging studies from animal data may suggest a need for higher dosages (>2mg/kg QD) of micafungin as those established for older children and adolescents.

In pediatric patients beyond the neonatal period up to the age of 12 years, many agents have not been fully evaluated. In this age group, voriconazole displays linear pharmacokinetics with adult dosages and considerably lower exposures; dosage escalation to higher dosages and pharmacokinetic modeling has led to a preliminary dosage for this age group that is currently being validated in therapeutic clinical trials. Caspofungin requires higher doses relative to adult patients based on a faster clearance rate, and dosing in children is based on body surface area scheme. The clearance of micafungin also is faster in infants and younger children, but it is dosed on a mg/kg platform. Finally, the pediatric development of posaconazole and anidulafungin is still ongoing, and both agents are not licensed yet in pediatric age groups.