ALBERT

Description: Fungi from the Candida genus are widespread commensals and, at the same time, are the leading cause of fungal infections worldwide. For instance, vulvovaginal candidiasis (VVC) affects approximately 75% of women at least once in their lifetime, remaining the second most common gynecological infection. On the contrary, hospital-acquired fungal bloodstream infections (BSIs), although less frequent, are characterized by a high mortality rate. Undoubtedly, the main reason for this situation are virulence factors that these yeast-like fungi can produce, and the ability to form a biofilm is one of the most important of them.. Due to the low effectiveness of classic antimycotics against Candida biofilms, an intense search for new drugs capable of eradicating this structure is highly demanded. One of the most promising groups of compounds exhibiting such properties are antimicrobial peptides (AMPs). This study focuses on a comparison of the efficacy of Omiganan and fluconazole alone and in combination against Candida strains isolated from BSIs. The obtained results are consistent with our previous reports on the effectiveness of Omiganan against clinical strains isolated from VVC. This is also the first report on the combinatory application of Omiganan in the context of fungal BSI. The majority of combinations with fluconazole showed an additive effect, as well as a synergistic effect in the range of certain concentrations. Importantly, such effects are visible at concentrations much lower than for those compounds used individually. Potentially, this entails the possibility of limiting the adverse effects (e.g., toxicity) of Omiganan and fluconazole applied in vivo, thus improving the safety profile of this particular antifungal therapy.

Description: Vulvovaginal candidiasis (VVC) occurs in over 75% of women at least once during their lifetime and is an infection that significantly affects their health. Candida strains resistant to standard azole antifungal therapy and relapses of VVC are more and more common. Hypothetically, biofilm is one of the main reasons of relapses and failure of the therapy. Ultrashort cationic lipopeptides (USCLs) exhibit high antimicrobial activities. Our previous study on USCLs revealed that disulfide cyclization can result in selective antifungal compounds. Therefore, four USCL were selected and their antifungal activity were studied on 62 clinical strains isolated from VVC. The results confirmed previous premises that cyclic analogs have increased selectivity between fungal cells and keratinocytes and improved anticandidal activity compared to their linear analogs against both planktonic and biofilm cultures. On the other hand, linear lipopeptides in combination with fluconazole showed a synergistic effect. It was found that the minimum inhibitory concentrations of the tested compounds in combination with fluconazole were at least four times lower than when used separately. Our results indicate that combination therapy of VVC with USCLs and fluconazole at low non-toxic concentrations can be beneficial owing to the synergistic effect. However, further in vivo studies are needed to confirm this hypothesis.