Liposomal and Deoxycholate Amphotericin B Formulations: Effectiveness against Biofilm Infections of Candida spp.

Célia Rodrigues,Mariana Henriques

doi:10.3390/pathogens6040062

Abstract

Background: candidiasis is the primary fungal infection encountered in patients undergoing prolonged hospitalization, and the fourth leading cause of nosocomial bloodstream infections. One of the most important Candida spp. virulence factors is the ability to form biofilms, which are extremely refractory to antimicrobial therapy and very difficult to treat with the traditional antifungal therapies. It is known that the prophylaxis or treatment of a systemic candidiasis are recurrently taken without considering the possibility of a Candida spp. biofilm-related infections. Therefore, it is important to assess the effectiveness of the available drugs and which formulations have the best performance in these specific infections. Methods: 24-h-biofilms of four Candida spp. and their response to two amphotericin B (AmB) pharmaceutical formulations (liposomal and deoxycholate) were evaluated. Results: generally, Candida glabrata was the less susceptible yeast species to both AmBs. MBECs revealed that it is therapeutically more appealing to use AmB-L than AmB-Deox for all Candida spp. biofilms, since none of the determined concentrations of AmB-L reached 10% of the maximum daily dose, but both formulations showed a very good capacity in the biomass reduction. Conclusions: the liposomal formulation presents better performance in the eradication of the biofilm cells for all the species in comparison with the deoxycholate formulation.

Highlights

Infections caused by Candida spp. have increased significantly in the past 30 years, becoming a substantial cause of morbidity and mortality
Candida spp. pathogenicity is mediated by a number of virulence factors, including the ability to adhere to medical devices and to host cells, which often leads to the formation of biofilms [4]
Fewer researchers have performed studies on the activity of the two formulations on matured biofilms [32,33]. Since these communities are known to be responsible for the most aggressive systemic infections [2], the aim of this study was to evaluate the efficacy of the amphotericin B (AmB) liposomal formulation (AmbiSome® ) compared to the original, deoxycholate (Fungizone® ) in eliminating the cells derived from matured biofilms of the four most common Candida spp. found in hospitals: Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis

Summary

Introduction

Infections caused by Candida spp. have increased significantly in the past 30 years, becoming a substantial cause of morbidity and mortality. This is critical in immunologically compromised individuals, and in patients submitted to continuous treatment with broad-spectrum antibiotics, to invasive procedures, and with medically implanted devices, which can cause both superficial and systemic infections [1,2]. Candida albicans is, generally, the most frequently isolated species, there has been a noteworthy upsurge in the frequency of non-Candida albicans. Candida (NCAC) species, such as Candida glabrata, Candida parapsilosis and Candida tropicalis [3]. Biofilm development on medical devices can cause the failure of the device and may turn into a source of future infection [6,7,8]

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