Question:
Do you know of any research indicating fungal or mould susceptibility to quinine analogues such as chloroquine or plaquenil or the quinolones, like ciprofloxacin?
Answer:
The antimalarial drug chloroquine has been shown to have in vitro antifungal activity against some fungi including Penicillium marneffei, Histoplasma capsulatum, and Cryptococcus neoformans, but the clinical utility has not been established.
The mechanisms of action are also under investigation. Chloroquine inhibits growth of H. capsulatum by pH-dependent iron deprivation, but is directly toxic to C. neoformans, possibly by pH disturbances in acidic vesicles [Weber, Boelart], however, in other fungi, other as yet undefined fungal targets are responsible for the observed antifungal activity.
Recently, research of combination therapy (using two antifungal drugs with distinct and different fungal targets) against experimental fungal disease has been on the increase.
As examples, the quinolones, such as ciprofloxacin in combination with fluconazole were effective in the treatment of experimental pulmonary mucormycosis, caused by Rhizopus oryzae in a mouse model [Sugar].
In a recent presentation, it was shown that Chloroquine has varying degrees of activity against various Candida species in combinations with fluconazole or itraconazole [Park].
Thus, while there is ongoing research into the antifungal activity of quinine analogs against a variety of yeasts and moulds, it appears that it will be some time before resistance issues are fully addressed.
Reference:
Weber SM, Levitz SM, Harrison TS. Chloroquine and the fungal phagosome. Curr Opin Microbiol. 2000 Aug;3(4):349-53.
Boelaert JR, Appelberg R, Gomes MS, Blasi E, Mazzolla R, Grosset J, Lounis N, Soteriadou K, Thiakaki M, Taramelli D, Tognazioli C. Experimental results on chloroquine and AIDS-related opportunistic infections. J Acquir Immune Defic Syndr. 2001 Mar 1;26(3):300-1
Sugar AM, Liu XP. Combination antifungal therapy in treatment of murine pulmonary mucormycosis: roles of quinolones and azoles. Antimicrob Agents Chemother. 2000 Jul;44(7):2004-6.
Park Y, Chang K, Choi J, Park Y, Cho J, Han S, Chin B, Choi S, Song Y, Kim J. Chloroquine (CQ) Potentiates Antifungal Agents against Candida spp.
43rd ICAAC Abstracts, American Society for Microbiology, September, 2003, page 471, Abstract: M-1246