Background
Although 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.
Methods
In 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.
Results
Polymyxin 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.
Conclusion
colistin could be proposed, in clinical practice, in association with other antifungals, to treat life-threatening fungal infections caused by MDR yeasts or moulds.