Artemisinins, New Miconazole Potentiators Resulting in Increased Activity against Candida albicans Biofilms

Cremer, Kaat De; Lanckacker, Ellen; Cools, Tanne; Bax, Marijke; Brucker, Klaas De; Cos, Paul; Cammue, Bruno P. A.; Thevissen, Karin

doi:10.1128/aac.04229-14

Cited by 67 publications

(68 citation statements)

References 40 publications

(46 reference statements)

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“…They found that artemisinin could inhibit the growth of brine shrimp even at the lowest tested concentration (0Á09 mg ml À1 ), and the brine shrimps were all dead within 1 h of incubation, indicating the high toxicity level of artemisinin against the growth of brine shrimps. In addition, a synergistic effect could not be observed between artesunate and FLC, but artesunate could increase the activity of miconazole against C. albicans biofilms (De Cremer et al 2015).…”

Section: Artemisininmentioning

confidence: 88%

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Antifungal activity of immunosuppressants used alone or in combination with fluconazole

et al. 2018

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Summary Fungal infections remain a challenge to clinicians due to the limited available antifungals. With the increasing use of antifungals in clinical practice, drug resistance has been emerging continuously, especially to fluconazole (FLC). Thus, a search for new antifungals and approaches to overcome antifungal resistance is needed. However, the development of new antifungals is usually costly and time consuming; discovering the antifungal activity of non‐antifungal agents is one way to address these problems. Interestingly, some researchers have demonstrated that several classes of immunosuppressants (calcineurin inhibitors, glucocorticoids, etc) also displayed potent antifungal activity when used alone or in combination with antifungals, especially with FLC. Some of them could increase FLC's susceptibility against resistant Candida albicans significantly reversing fungal resistance to FLC. This article reviews the antifungal activities of immunosuppressants used alone or in combination with antifungals and their potential antifungal mechanisms that have been discovered so far. Although immunosuppressive agents have been identified as risk factors for fungal infection, we believe these findings are very important for overcoming drug resistance and developing new antifungals.

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Section: Artemisininmentioning

confidence: 88%

“…In addition, a synergistic effect could not be observed between artesunate and FLC, but artesunate could increase the activity of miconazole against C. albicans biofilms (De Cremer et al . ).…”

Section: The Antifungal Activity Of Traditional Chinese Medicinementioning

confidence: 97%

Antifungal activity of immunosuppressants used alone or in combination with fluconazole

et al. 2018

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“…De Cremer and colleagues (2015) found that miconazole and artemisinins combination have the potential to treat infection caused by biofilm formation of one strain of C. albicans. Artemisinins are antimalarial drugs that were found to act synergistically with miconazole because of dihydroartemisinin, a structural homologue of artesunate, a semisynthetic derivative of artemisinin, and its ability to increase the capability of miconazole against biofilms of C. albicans (De Cremer et al, 2015). Furthermore, another study conducted by De Cremer and colleagues (2016) also showed that combination of miconazole (125µM) to antimycin A (25µM) exhibited high superoxide induction, which is significant to fungicidal compounds and their production of ROS to increase susceptibility of miconazole to biofilms.…”

Section: Discussionmentioning

confidence: 99%

In vitro Resistance Pattern of Selected Antifungal Azoles against Candida albicans Biofilms on Silicone Nasogastric Tube

Sumalapao¹,

Salazar²,

Alegre³

et al. 2019

J Pure Appl Microbiol

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Prolonged use of implanted medical devices has been linked with device-associated infections. Since enteral tube feeding is increasing worldwide, the present study described the morphology of Candida albicans biofilms on the surface of silicone nasogastric tube (NGT) using fluorescence microscopy. With the emergence of multidrug-resistant fungal infections, the present study assessed the susceptibility profile of the biofilms to antifungal azoles namely fluconazole, miconazole, voriconazole, and posaconazole using the standard disc diffusion method. Microscopic studies of C. albicans biofilms revealed a complex heterogeneous structure with yeast cells and hyphal elements entrenched within a polysaccharide matrix. Planktonic C. albicans cells remained susceptible with posaconazole, fluconazole, miconazole, and voriconazole. However, the fungal biofilms exhibited resistance with miconazole. There was a significant reduction in the zone of inhibition on the 24-h, 48-h, and 72-h biofilm formation with posaconazole, voriconazole, and fluconazole, respectively. Kinetic investigation on C. albicans biofilm with posaconazole revealed a zero-order kinetic profile (R 2 =0.9774) whereas with voriconazole exhibited a first-order kinetic profile (R 2 =0.9974). These findings can possibly provide information regarding the resistance of fungal biofilms with antifungal azoles. Demonstration of common biofilm features will extend the findings of this study beyond fungi to polymicrobial infections, as new information and insights will influence several disciplines ranging from environmental microbiology to pharmaceutical drug design intended for biofilm-associated infections.

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“…Artemisinins are currently used for treatment of malaria [88], as is chloroquine. These data point to the potential of combination therapy consisting of azoles and antimalarial compounds to treat C. albicans biofilm-related infections [87].…”

Section: Antimicrobial Compoundsmentioning

confidence: 98%

“…De Cremer and co-workers screened a repositioning compound library in the search for miconazole potentiating molecules to treat mature C. albicans biofilms [87]. After screening the Pharmakon 1600 repositioning library, three components exhibited synergy with miconazole: hexachlorophene, pyrvinium pamoate and artesunate.…”

Section: Antimicrobial Compoundsmentioning

confidence: 98%

Combinatorial drug approaches to tackleCandida albicansbiofilms

Cremer

Staes

Delattin

et al. 2015

Expert Review of Anti-infective Therapy

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The human fungal opportunistic pathogen Candida albicans resides in the human gut, genitourinary tract and on the skin. The majority of infections caused by C. albicans are biofilm-related. In the first part of this review, we discuss new insights into C. albicans biofilm characteristics, concentrating on the extracellular matrix, phenotypic switching, efflux pumps and persister cells. It is widely accepted that this multicellular lifestyle is more resistant to traditional antifungal treatment compared to free-living cells. Therefore, much effort is put in the search for combinations of drugs leading to synergistic interactions against microbial biofilms to achieve lower effective doses of the drugs. In the second part of this manuscript, we review all recently identified compounds that act synergistically with azoles, echinocandins and/or polyenes against C. albicans biofilms.

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Artemisinins, New Miconazole Potentiators Resulting in Increased Activity against Candida albicans Biofilms

Cited by 67 publications

References 40 publications

Antifungal activity of immunosuppressants used alone or in combination with fluconazole

Antifungal activity of immunosuppressants used alone or in combination with fluconazole

In vitro Resistance Pattern of Selected Antifungal Azoles against Candida albicans Biofilms on Silicone Nasogastric Tube

Combinatorial drug approaches to tackleCandida albicansbiofilms

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