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Recent developments on the anti-Candida effect of amphotericin B combined with a second drug- a mini-review

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ACAD BRASILEIRA DE CIENCIAS
DOI: 10.1590/0001-3765202320220033

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Amphotericin B; antifungal activity; Candida spp; checkerboard; synergism; yeast

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Invasive Candida infections are becoming increasingly resistant to available antifungal agents, highlighting the need for alternative therapies. Amphotericin B (AMB) is the gold standard treatment, but its clinical use is limited due to toxicity. Combining AMB with other substances may reduce toxicity and enhance antifungal activity, particularly those targeting the plasma membrane. This mini-review summarizes compounds that have shown synergistic effects with AMB and highlights the potential of these combination therapies for treating Candida infections.
Invasive Candida infections threaten human health due to the increasing incidence of resistance to the currently available antifungal agents. Amphotericin B (AMB) is the gold standard therapy to treat these infections. Nevertheless, the use of such substance in the clinic is aggravated by its toxicity. Since AMB binds to membrane sterols, it forms pores on human plasma membranes, mainly in kidney cells, leading to nephrotoxicity. The combination of this drug to a second substance could allow for the use of smaller concentrations of AMB, consequently lowering the probability of adverse effects. This mini-review summarizes information regarding an array of substances that enhance AMB antifungal activity. It may be noticed that several of these compounds target plasma membrane. Interestingly, substances approved for human use also presented combinatory anti-Candida activity with AMB. These data reinforce the potential of associating AMB to another drug as a promising therapeutical alternative to treat Candida infections. Further studies, regarding mechanism of action, pharmacokinetics and toxicity parameters must be conducted to confirm the role of these substances as adjuvant agents in candidiasis therapy.

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