Randomized Pharmacokinetic Study of Fluconazole and Micafungin in Preterm Neonates with Suspected or Proven Fungal Infection

Abstract

Introduction: Neonatal Candida infection requires urgent treatment because of high risk disease with possible central nervous system infection. Fluconazole prophylaxis is recommended in NICUs with a high incidence in fungal infections. Both fluconazole and micafungin are used for treatment in preterm and term neonates with proven or only suspected fungal infection, as candida infection is difficult to prove. Although fluconazole dose recommended in the marketing authorization is 6 mg/kg/day in neonates, maintenance doses currently used in NICUs in Europe is often higher, between 6 and 12 mg/kg. For Micafungin, the available data support the idea that only dosages greater than recommended (2 to 4 mg/kg/day) may ensure adequate coverage of the CNS. The drug-exposure target recommended for fluconazole is at least 400 mg*h/L and for micafungin is at least 166.5 mg*h/L. In this context, the current study is designed to further elucidate the pharmacokinetics of the two drugs in preterm neonates.