Antifungal Agents for the Treatment of Systemic Fungal Infections in Children

Abstract

Traditionally, the mainstay of systemic antifungal therapy has been amphotericin B deoxycholate (conventional amphotericin B). Newer agents have been developed to fulfill special niches and to compete with conventional amphotericin B by virtue of having more favourable toxicity profiles. Some agents have displaced conventional amphotericin B for the treatment of specific fungal diseases. For example, voriconazole has emerged as the preferred treatment for invasive pulmonary aspergillosis. This notwithstanding, conventional amphotericin B remains a useful agent for the treatment of paediatric fungal infections. Knowledge of the characteristics of the newer agents is important, given the increasing numbers of patients who are being treated with these drugs. Efforts need to be directed at research aimed at generating paediatric data where these are lacking. The antifungal agents herein described are most often used as monotherapy regimens because there is no uniform consensus on the value of combination therapy, except for specific scenarios.

Rhinomaxillary Mucormycosis in a Renal Transplant Recipient: Case Report

“…However, the major toxicities associated with amphotericin B are nephrotoxicity and infusion-related events (chills and fever). 13,14 The liposomal amphotericin B is less nephrotoxic, with comparable effectiveness relative to amphotericin B deoxycholate. The lipid products might be advantageous, because higher doses per unit body weight can be used while preserving renal function.…”

“…These products are usually recommended in patients who are refractory to, or intolerant of, commercial amphotericin B deoxycholate. 14,15 Because amphotericin B cannot distribute itself through necrotic tissues, local debridement of infected structures is necessary. 15 Our patient was a kidney allograft recipient with a predisposing factor of immunosuppression.…”

Targeted antifungal liposomes

“…Even with antifungal therapy, however, one-year survival among immunocompromised patients with aspergillosis is only 25 to 60%. Furthermore, all known antifungal agents that treat aspergillosis are quite toxic to human cells(5, 6). The goal of our research has been to develop a targeted liposomal strategy that improves antifungal drug delivery and enhances therapeutic efficacy.…”

“…Because AmB binds the fungal plasma membrane sterol ergosterol more efficiently than the mammalian sterol cholesterol, AmB is more toxic to fungal cells. The side effects of Amphotericin B include neurotoxicity and/or nephrotoxicity and/or hepatoxicity (5, 6) and can result in death of the patient (1).…”

“…Amphotericin B loaded liposomes, AmB-LLs, penetrate more efficiently to various organs (7, 8), penetrate the cell wall (9) and show reduced toxicity at higher, more effective doses of AmB than the second most commonly used AmB product, deoxycholate detergent-solubilized AmB (5, 6, 10, 11). AmB is an amphipathic molecule.…”