Antifungal Drugs for Invasive Candida Infections (ICI) in Neonates: Future Perspectives

Abstract

Fungal infections may complicate the neonatal clinical course, and the spectrum of therapies for their treatment in the perinatal period is limited. Polyenes, Azoles and Echinocandins represent the three classes of antifungal drugs commonly used in the neonatal period. The present review provides an overview about the most recent therapeutic strategies for the treatment of fungal infections in neonates.

Therapeutic Drug Monitoring Is a Feasible Tool to Personalize Drug Administration in Neonates Using New Techniques: An Overview on the Pharmacokinetics and Pharmacodynamics in Neonatal Age

“…treatment-resistant or aspergillosis in neonates and infants have been described [100][101][102]. Table 2 summarizes antifungals currently used in neonatal age that are titrated with TDM [103,104]. Fluconazole has a direct correlation between the administered dose and the plasma concentration, so TDM is not routinely required in the clinical practice [26,105].…”

“…Table 2. Pharmacokinetics of most common antifungals titrated with TDM in newborns (modified from Roberts et al [103] and Bersani et al [104]). iv, intravenous.…”

“…Table 2 summarizes antifungals currently used in neonatal age that are titrated with TDM [ 103 , 104 ].…”

Plant-Derived Substances in the Fight Against Infections Caused by Candida Species

“…All of them are natural components isolated from bacteria from the Streptomyces genus. AMB is produced by S. nodosus [ 59 ], natamycin by S. natalensis, S. chattanoogensis, S. lydicus and S. gilvosporeus [ 60 ], and nystatin by S. noursei [ 61 ]. These highly lipophilic macrolides are able to penetrate the phospholipid bilayer of the plasma membrane, in which they bind to ergosterol and promote the formation of transmembrane channels resulting in cellular ionic imbalance and leading to cell death [ 62 ].…”

“…These drugs act by binding and inhibition of the lanosterol-14α-demethylase, a cytochrome P450 enzyme (the product of ERG11 gene) mediating a rate-limiting step in ergosterol biosynthesis. This results in the formation of toxic sterols (14-α-methylsterols), placed loosely within lipid bilayers and decreasing tightness and stability of fungal cell membrane [ 59 ]. This group of synthetic fungistatic drugs includes imidazoles (clotrimazole, econazole, miconazole and ketoconazole), used primarily for the treatment of superficial infections, and triazoles (fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole) preferred for fighting against invasive candidiasis [ 65 , 66 , 68 ].…”