Eumycetoma causative agents are inhibited in vitro by luliconazole, lanoconazole and ravuconazole

Abstract

Introduction Eumycetoma is a subcutaneous mutilating disease that can be caused by many different fungi. Current treatment consists of prolonged itraconazole administration in combination with surgery. In many centres, due to their slow growth rate, the treatment for eumycetoma is often started before the causative agent is identified. This harbours the risk that the causative fungus is not susceptible to the given empirical therapy. In the open‐source drug program MycetOS, ravuconazole and luliconazole were promising antifungal agents that were able to inhibit the growth of Madurella mycetomatis, the most common causative agent of mycetoma. However, it is currently not known whether these drugs inhibit the growth of other eumycetoma causative agents. Materials and methods Here, we determined the in vitro activity of luliconazole, lanoconazole and ravuconazole against commonly encountered eumycetoma causative agents. MICs were determined for lanoconazole, luliconazole and ravuconazole against 37 fungal isolates which included Madurella species, Falciformispora senegalensis, Medicopsis romeroi and Trematosphaeria grisea and compared to those of itraconazole. Results Ravuconazole, luliconazole and lanoconazole showed high activity against all eumycetoma causative agents tested with median minimal inhibitory concentrations (MICs) ranging from 0.008–2 µg/ml, 0.001–0.064 µg/ml and 0.001–0.064 µg/ml, respectively. Even Ma. fahalii and Me. romeroi, which are not inhibited in growth by itraconazole at a concentration of 4 µg/ml, were inhibited by these azoles. Conclusion The commonly encountered eumycetoma causative agents are inhibited by lanoconazole, luliconazole and ravuconazole. These drugs are promising candidates for further evaluation as potential treatment for eumycetoma.

In vitro antifungal susceptibility profile of Iranian Fusarium isolates: Emphasising on the potent inhibitory effect of efinaconazole compared to other drugs

“…In the current study, three antifungals comprising luliconazole, lanoconazole and efinaconazole demonstrated the highest antifungal activity among all tested. Several previous studies have shown that luliconazole and lanoconazole have excellent antifungal activity against the most clinically important fungi including Aspergillus , Candida , Malassezia and melanised fungi 29–33 . Among the triazoles tested in our study, efinaconazole had significantly higher activity than the others.…”

“…Several previous studies have shown that luliconazole and lanoconazole have excellent antifungal activity against the most clinically important fungi including Aspergillus, Candida, Malassezia and melanised fungi. [29][30][31][32][33] Among the triazoles tested in our study, efinaconazole had significantly higher activity than the others. Efinaconazole had a GM MIC of 0.98 μg/ml, which was higher than luliconazole (GM MIC 0.004 μg/ml) and lanoconazole (GM MIC 0.012 μg/ml) but lower than main options for fusariosis such as amphotericin B (1.03 μg/ml), voriconazole (2.03 μg/ml) and posaconazole (4.39 μg/ml).…”

In Vitro and In Vivo Effect of the Imidazole Luliconazole against Lomentospora prolificans and Scedosporium spp.

“…In its current topical formulation, LLCZ is effective only against superficial skin mycoses ( 17 ). Due to the low solubility of the drug, treatment of a deep-seated infection is challenging because of its retention in the skin ( 29 ). This could mean that the development of a systemic LLCZ treatment will not be straightforward.…”

“…Aside from the unknown mechanism of action, and the unavailability of an oral formulation, LLCZ has also shown a poor solubility and retention in the skin. However, the drug shows no concerning side effects, and oral formulations have yielded good results in murine models during its development phase ( 29 ).…”

Clinical Manifestations of Human Exposure to Fungi

“…Eumycetoma treatment includes the use of oral antifungal medication (i.e., itraconazole, ketoconazole, lanoconazole, luliconazole, posaconazole, ravuconazole, voriconazole). Nevertheless, more complex and incontrollable cases may require surgery and amputation [ 191 , 192 , 193 ]. Several phytotherapeutic alternatives, such as Acacia nubica , Nigella sativa , Boswellia papyrifera , Melaleuca alternifolia , Moringa oleifera , Zingiber officinalis , Piper nigrum , Eugenia caryophillus , and Cinnamomum verum , have been suggested, with positive effects on the treatment of this disease [ 194 ].…”