Abstract
BackgroundAlthough antifungals are available and usually used against fungal infections, multidrug-resistant (MDR) fungal pathogens are a growing problem for public health. Moreover, fungal infections have become more prevalent nowadays due to the increasing number of people living with immunodeficiency. Thus, previously rarely-isolated and/or unidentified fungal species including MDR yeast and moulds have emerged around the world. Recent works indicate that polymyxin antibiotics (polymyxin B and colistin) have potential antifungal proprieties. Therefore, investigating the in vitro activity of these molecules against clinical multidrug-resistant yeast and moulds could be very useful.MethodsIn this study, a total of 11 MDR yeast and filamentous fungal strains commonly reported in clinical settings were tested against polymyxin antibiotics. These include strains belonging to the Candida, Cryptococcus and Rhodotorula yeast genera, along with others belonging to the Aspergillus, Fusarium, Scedosporium, Lichtheimia and Rhizopus mould genera. The fungicidal or fungistatic action of colistin against clinical yeast strains was determined by the time-kill study. Further, a checkerboard assay for its combination with antifungal agents, usually used in clinical practices (amphotericin B, itraconazole, voriconazole), was carried out against multi-drug resistant fungal strains.ResultsPolymyxin B and colistin exhibited an antifungal activity against all MDR fungal strains tested with MICs ranging from 16 to 128 μg/ml, except for the Aspergillus species. In addition, colistin has a fungicidal action against yeast species, with minimum fungicidal concentrations ranging from 2 to 4 times MICs. It induces damage to the MDR Candida albicans membrane. A synergistic activity of colistin-amphotericin B and colistin-itraconazole associations against Candida albicans and Lichtheimia corymbifera strains, respectively, and colistin-fluconazole association against Rhodotorula mucilaginosa, was demonstrated using a checkerboard microdilution assay.Conclusioncolistin could be proposed, in clinical practice, in association with other antifungals, to treat life-threatening fungal infections caused by MDR yeasts or moulds.
Highlights
Antifungals are available and usually used against fungal infections, multidrug-resistant (MDR) fungal pathogens are a growing problem for public health
Resistance phenotypic profiles of the emerging fungal pathogens used in this study The Minimum inhibitory concentration (MIC) obtained with the different antifungal classes tested against the 4 Candida spp. and Aspergillus spp
Our study demonstrated that polymyxin antibiotics have, aside from their antibactericidal activity, an antifungal activity, especially against multidrug-resistant Candida, Rhodotorula and Cryptococcus yeast isolates, and against resistant filamentous fungi, such as Scedosporium, Rhizopus and Lichtheimia species
Summary
Antifungals are available and usually used against fungal infections, multidrug-resistant (MDR) fungal pathogens are a growing problem for public health. Along with the Yousfi et al Antimicrobial Resistance and Infection Control (2019) 8:66 main mycosis agents, such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans [4], other life-threatening and emerging pathogens, including not previously well-identified/characterized species and opportunistic multidrug-resistant (MDR) ones, are increasingly reported. One major characteristic of these emerging fungal pathogens is their highly-resistant profile to antifungal drugs These disseminated infections caused by MDR yeasts and moulds are difficult to treat [6], leading to a significant increase of morbidity and mortality, in immunocompromised patients and in healthy individuals [7]. That is why many studies suggest to use other pharmacological classes and re-purposing old drugs either as a single antifungal agent or in combination with known antifungal drugs [10]
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