bone loss drugs. Researchers found that when azoles were combined with bisphosphonates, which are commonly used to treat osteoporosis and other bone conditions, the antifungal treatment was significantly more effective. In tests on human skin and in mice, the combination delayed the recurrence of fungal infections for several weeks. The researchers believe that bisphosphonates may enhance the effectiveness of azoles by reducing the production of ergosterol, a key component of the fungal cell wall. The study offers hope for more effective treatments for common fungal infections that affect millions of people worldwide.
The article discusses the potential use of bisphosphonates, which are commonly used to treat osteoporosis, in combination with azole antifungal drugs to effectively treat yeast infections caused by Candida and Cryptococcus species. This research, conducted by the same group that previously demonstrated the effectiveness of this combination for yeast infections, now extends the findings to include dermatophytes, which cause superficial infections.
The study proposes that bisphosphonates could be repurposed for use with azole antifungals, which are relatively non-toxic, and suggests that this combination could be easily tested in clinical studies.
The researchers note that there are few effective antifungal drugs available, and that fungi will inevitably develop resistance to them.According to senior author Dee Carter, a mycologist at the University of New South Wales, Australia, “Fungal infections can develop resistance to drugs over time, no matter how they are treated. However, using two drugs at the same time makes it much less likely for resistance to occur.”
Carter stated that the discovery of the synergistic effect in dermatophytes did not come as a complete surprise. This research project began several years ago when her team conducted genomic analyses on how pathogenic yeasts responded to drug treatment. The study led them to a genetic pathway that is “upstream” of the pathway targeted by azoles, and is instead targeted by bisphosphonates. “That’s often a good way to Targeting interlinked processes is key to getting drugs to work,” said Carter.
Carter and her team conducted experiments in the lab using three widely available bisphosphonates (risedronate, alendronate, and zoledronate) in combination with three commonly available azole antifungals (fluconazole, itraconazole, and ketoconazole). They tested these combinations on clinical isolates from various dermatophyte species responsible for superficial infections. The combination of zoledronate and ketoconazole was particularly effective against 8 out of 9 tested species and also prevented the development of resistance.
Aidan Kane, a mycologist and the lead author, also commented on the study.The drug combination was found to weaken the cell membrane, preventing the survival of the fungus. In addition to treating dermatophytes, the study also revealed potential for the drug combination to act against molds that cause invasive disease. This suggests potential clinical applications beyond superficial infections. Modifying the drugs may create a treatment that also works systematically.ly,” Carter said. “The next step is to continue testing bisphosphonate-azole combinations in animal models, and then test it in clinical trials.”
