In vitro polymyxin activity against clinical multidrug-resistant fungi.

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 , and yeast genera, along with others belonging to the , , , and 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 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 membrane. A synergistic activity of colistin-amphotericin B and colistin-itraconazole associations against and strains, respectively, and colistin-fluconazole association against 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.