The results of our current study revealed the potential in vitro effect of artesunate, chloramphenicol, and co-trimoxazole as antifungal, in particular against Basidiobolus spp., the etiological agent of basidiobolomycosis. This is not completely new since few studies have suggested this idea and but most trials have been carried out on a clinical-based treatment course of therapy [17, 31]. Nonetheless, in vitro evaluation of antifungal drugs and sulfamethoxazole-trimethoprim against clinical isolates of Conidiobolus lamprauges has been done . Conidiobolus lamprauges is a member of the order Entomophthorales, a species phylogentically related to Basidiobolus ranarum, Basidiobolus haptosporus or Conidiobolus coronatus, the later species are agents implicated in skin and abdominal basidiobolomycosis [23, 33].
Several conventional antifungal drugs, for example, potassium iodide, co-trimoxazole, amphotericin B, ketoconazole, and itraconazole, have been tried for the treatment of entomophthoromycosis due to Conidiobolus coronatus or basidiobolomycosis due to Basidiobolus ranarum or Basidiobolus haptosporus-like fungi with variable results . Comparably, information derived from a number of investigations indicated that non-antifungal compounds supplement the action of conventional antifungal agents either through the elimination of natural resistance or through exhibiting in some way activity antagonizing certain fungal species [21, 22, 31].
These results confirm the hypothesis that co-trimoxazole has an antifungal inhibitory, as reported previously . This substantiating that folic acid blockade may be a potential antifungal target for Basidiobolus species. This report of the antifungal potential of co-trimoxazole drug against this fungal pathogen support earlier one e [15, 16]. Potassium iodide and co-trimoxazole were found to be simple and effective for basidiobolomycosis treatment . While there is no consensus, African physicians prefer to use potassium iodide or trimethoprim-sulfamethoxazole in the treatment of tropical mycosis infections caused by either Basidiobolus ranarum, Basidiobolus haptosporus or Conidiobolus coronatus or others . Experience lead some physicians to adopt septrin (trimethoprim-sulfamethoxazole) as the drug of choice in the management of entomophthorosis due to Conidiobolus coronatus . Another study suggested using the combination of itraconazole and fluconazole as an additional option for the treatment of this mycosis, acting better than sulfamethoxazole plus trimethoprim for 2 months . A case of rhinophycomycosis entomophthora was successfully treated with a combination of bacteria, potassium iodide, and steroids were reported . Clinical isolates of Conidiobolus lamprauges (entomophthoromycosis cases) showed synergistic interactions of 100% for the sulfamethoxazole-trimethoprim combination, 71% for the terbinafine-azole antifungal combination, and 29% for the terbinafine-micafungin combination. All other interactions were indifferent .
The mode of action of these three drugs is known against their conventional target organisms. It is, however, that the effect on fungi is still unknown. The inhibition of folic acid synthesis by Coccidioides posadasii has been speculated as a likely antifungal target . Saccharomyces cerevisiae in response to treatment with arsenic has revealed a complex response that influences signaling pathways, including protein kinases such as the mitogen-active protein kinase and target of the rapamycin complex 1 system . The modes of action of artesunate continue to be unclear and debatable . On the other hand, chloramphenicol is a bacteriostatic that acts via inhibiting protein synthesis. It prevents protein chain elongation by inhibiting the peptidyl transferase activity of the bacterial ribosome . However, it not known how it might affect the eukaryotic fungi.
Our data support the fact that artesunate is a potential antifungal as well as its primary antimalarial activity . Data have suggested the enhancement of artesunate with miconazole in antagonizing Candida’s biofilm. These refer to the potential mixture treatment of Candida albicans biofilm-related infections. The results of our current study support the use of “non-antifungal antibacterial drugs as effective against Basidiobolus strains, which support their earlier antifungal effects [18, 20]. The combined effect of artesunate + voriconazole and that of co-trimoxazole + voriconazole have significant synergic effects, p = 0.003 and p = 0.021, respectively. These are hopeful results for the treatment of GIB in humans, which need in vivo application and determining the clinical implications.
In conclusion, the results of the present study demonstrated a clear inhibitory antagonism of artesunate, co-trimoxazole, and a less significant effect in the case of chloramphenicol, against strains of Basidiobolus. These are encouraging results for the in vivo application on human or animal models. The in vivo application is necessary to be combined with standard antifungal drugs rather than a single therapy since our results have indicated a synergistic effect between co-trimoxazole and voriconazole, with a lesser effect between chloramphenicol and voriconazole, but markedly between artesunate and voriconazole. The study recommends the application of artesunate + voriconazole or co-trimoxazole + voriconazole in a clinical trial.