Treatment of invasive fungal infections in immunocompromised and transplant patients: AmBiLoad Trial and other new data

Abstract

Opportunistic invasive fungal infections (IFIs) have changed. Moreover, a significantly greater therapeutic armamentarium is now available, with liposomal amphotericin B (L-AmB) administered in new ways, for example in higher doses, in combination with other compounds or inhaled. The objective of this study was to review these three aspects. The AmBiLoad study was designed to clarify whether higher doses of L-AmB could be more efficacious than the licensed dose of 3–5 mg/kg. It was a multicentric study where patients were randomised to receive a 14-day course of 3 mg/kg/day or 10 mg/kg/day L-AmB. A total of 339 patients were enrolled during the study period (April 2003 to October 2004). Discontinuation of treatment, mainly due to adverse events, was frequent (13% in the standard dose group vs. 24% in the high dose group), and only 66% and 50%, respectively, completed 14 days of randomised treatment. There was no statistically significant difference with regard to favourable overall responses between the treatment groups (50% in the standard dose group vs. 46% in the high dose group; P = 0.65). In addition, there was no significant difference according to type of IFI (invasive aspergillosis, 50% vs. 46% in the standard and high dose groups, respectively). The obvious conclusion of this study was that administration of 10 mg/kg/day L-AmB to patients with IFI does not improve efficacy but increases toxicity and price. In vitro and experimental data suggest that the combination of AmB with other antifungal agents may be more effective than monotherapy; however, data regarding the clinical efficacy of L-AmB in combination with other agents are scarce. The use of inhaled L-AmB has shown promising results for use as antifungal prophylaxis in high-risk patients.