Absent In Vitro Interaction between Chloroquine and Antifungals Against Aspergillus fumigatus

S. Seyedmousavi1 , H. van der Lee2 , P. Verweij2 , A. Warris3

Author address: 

Erasmus Univ. Med. Ctr., Rotterdam, Netherlands, 2Radboud Univ. Med. Ctr., Nijmegen, Netherlands, 3Univ. of Aberdeen, Aberdeen, United Kingdom

Abstract: 

Background: The efficacy of voriconazole, the recommended first choice drug to treat infections caused by Aspergillus fumigatus, might be hampered by the emergence of azole resistance. Therefore, it is important to explore alternative treatment strategies. The antimalarial drug chloroquine in combination with antifungals has shown to have a direct antifungal effect on both azole-susceptible and azole-resistant Candida albicans isolates. We therefore investigated whether chloroquine potentiate synergistic activity in combination with antifungals for the treatment of Aspergillus fumigatus. Methods: The in vitro interaction between chloroquine and voriconazole or amphotericin B or caspofungin was determined against voriconazole-susceptible and voriconazole-resistant clinical A. fumigatus isolates using a checkerboard microdilution method with spectrophotometric analysis and a viability-based XTT {2,3-bis(2-methoxy-4-nitro- 5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide} assay within 2 h of exposure after 24 and 48 h of incubation at 35°C to 37°C. Results: Our studies showed that presence of chloroquine had no growth-inhibitory antifungal activities against clinical A. fumigatus isolates, either voriconazole-susceptible or resistant. In addition, no obvious interactions were found in vitro for all the combinations tested. Conclusions: In conclusion, chloroquine, alone or in combination with different classes of antifungal agents, did not show any in vitro inhibitory antifungal activity against A. fumigatus. Our previous observation that chloroquine increases the antifungal activity of neutrophils may however suggests that chloroquine exerts different effects in vivo and its role in the treatment of Aspergillus infections remains to be further assessed.
2016

abstract No: 

SUNDAY-426

Full conference title: 

ASM Microbe 2016
    • ASM microbe 1st (2016)