Effect of caspofungin and micafungin in combination with farnesol against Candida parapsilosis biofilms

Kovács, Renátó; Bozó, Aliz; Gesztelyi, Rudolf; Domán, Marianna; Kardos, Gábor; Nagy, Fruzsina; Tóth, Zoltán; Majoros, László

doi:10.1016/j.ijantimicag.2016.01.007

Cited by 50 publications

(99 citation statements)

References 29 publications

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“…The percentile change in metabolic activity caused by drug exposure was calculated as followed: 100 × [(A well – A background )/(A drug‐free well – A background )], where A is the absorbance measured. The background was measured from the fungus‐free well . All isolates were tested in three independent experiments, and the median of the three values was used for further analysis.…”

Section: Methodsmentioning

confidence: 99%

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Candida biofilm production is associated with higher mortality in patients with candidaemia

Vitális

Nagy

Tóth

et al. 2020

Mycoses

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Summary Background Candidaemia is a common life‐threatening disease among hospitalised patients, but the effect of the Candida biofilm‐forming ability on the clinical outcome remains controversial. Objective The aim was to determine the impact of biofilms, specifically focusing on biofilm mass and metabolic activity, on the mortality in candidaemia. Patients/Methods The clinical data of patients (n = 127) treated at the University of Debrecen, Clinical Centre, between January 2013 and December 2018, were investigated retrospectively. Biofilm formation was assessed using the crystal violet and XTT assays, measuring the biofilm mass and metabolic activity, respectively. Isolates were classified as low, intermediate and high biofilm producers both regarding biofilm mass and metabolic activity. The susceptibility of one‐day‐old biofilms to fluconazole, amphotericin B, anidulafungin, caspofungin and micafungin was evaluated and compared to planktonic susceptibility. Results Intermediate/high biofilm mass was associated with significantly higher mortality (61%). All Candida tropicalis, Candida parapsilosis and Candida glabrata isolates originating from fatal infections were intermediate/high biofilm producers, whereas this ratio was 85% for Candida albicans. Solid malignancy was associated with intermediate/high biofilm producers (P = .043). The mortality was significantly higher in infections caused by Candida strains producing biofilms with intermediate/high metabolic activity (62% vs. 33%, P = .010). The ratio of concomitant bacteraemia was higher for isolates forming biofilms with low metabolic activity (53% vs 28%, P = .015). Conclusions This study provides evidence that the Candida biofilms especially with intermediate/high metabolic activity are related to higher mortality in candidaemia.

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Section: Methodsmentioning

confidence: 99%

“…The activity of tested antifungals against biofilms was assessed using the XTT assay . The concentrations tested in MIC determination against biofilms were 0.06‐512 mg/L, 0.015‐8 mg/L and 0.008‐4 mg/L for fluconazole, amphotericin B and the tested echinocandins, respectively.…”

Section: Methodsmentioning

confidence: 99%

Candida biofilm production is associated with higher mortality in patients with candidaemia

Vitális

Nagy

Tóth

et al. 2020

Mycoses

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“…The tested concentration ranges were the same as described above for biofilm MIC determination. FICIs was calculated using the following formula: ΣFIC = FIC A + FIC B = MIC A comb /MIC A alone + MIC B comb /MIC B alone , where MIC A alone and MIC B alone stand for MICs of drugs A and B when used alone, and MIC A comb and MIC B comb represent the MIC values of drugs A and B in combination at isoeffective combinations respectively (Kovács et al ; Van Dijck et al ). FICI was determined as the lowest ΣFIC.…”

Section: Methodsmentioning

confidence: 99%

“…To further analyse echinocandin‐nikkomycin Z interactions, MacSynergy II was used, which employs the Bliss independence algorithm to determine synergy. The Bliss independence model is defined by the equation E ab = E a + E b − (E a E b ), where E ab is the additive effect of compounds a and b as predicted by their individual effects (E a and E b ) (Kovács et al ; Lai et al ). The obtained E values of each combination were presented on the z ‐axis in the three‐dimensional plot.…”

Section: Methodsmentioning

confidence: 99%

Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms

Kovács

Nagy

Tóth

et al. 2019

Lett Appl Microbiol

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Antifungal lock therapy has received significant interest in the last few years because the frequently usage of intravascular devices is associated with an increasing number of catheter‐related bloodstream infections caused by Candida species. Antifungal combinations with synergistic interaction can be a good choice for antifungal lock therapy; therefore, interactions were examined between two echinocandins (caspofungin and micafungin) and the chitin synthesis inhibitor nikkomycin Z against Candida albicans and C. parapsilosis biofilms. Susceptibility was evaluated using the XTT‐based checkerboard microdilution method, while the nature of interactions was assessed by calculating fractional inhibitory concentration indices and using the Bliss independence model. Mathematic‐based evaluations were supplemented with fluorescent LIVE/DEAD viability assay. The results obtained by statistical interaction analyses correlated well with the viability assay. The tested echinocandins with nikkomycin Z caused an extended cell death and the structure of the biofilm was sparse compared to the control, especially for C. albicans. The findings support the simultaneous usage of nikkomycin Z and caspofungin or micafungin in alternative therapies such as the antifungal lock therapy. Significance and Impact of the Study Antifungal lock therapy can be a potential therapeutic approach to eradicate the intraluminal Candida biofilms; however, there is no approved lock strategy against fungal species so far. The results of this study provide valuable evidence that nikkomycin Z acts synergistically in combination with caspofungin or micafungin against biofilms. In addition, this synergy was more pronounced for micafungin combined with nikkomycin Z. Therefore, nikkomycin Z can be considered as a potential agent in antifungal lock therapy especially with micafungin against C. albicans or C. parapsilosis biofilms.

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“…Both echinocandins could clear the biofilm, but were up to 64-fold more effective when combined with farnesol. Interestingly, micafungin could not clear biofilms older than 24 h [142].…”

Section: From Papulacandins and Echinocandins To Drugs Against Fungalmentioning

confidence: 95%

Fungal Metabolites for the Control of Biofilm Infections

Estrela

Abraham

2016

Agriculture

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Many microbes attach to surfaces and produce a complex matrix of polymers surrounding their cells, forming a biofilm. In biofilms, microbes are much better protected against hostile environments, impairing the action of most antibiotics. A pressing demand exists for novel therapeutic strategies against biofilm infections, which are a grave health wise on mucosal surfaces and medical devices. From fungi, a large number of secondary metabolites with antimicrobial activity have been characterized. This review discusses natural compounds from fungi which are effective against fungal and bacterial biofilms. Some molecules are able to block the cell communication process essential for biofilm formation (known as quorum sensing), others can penetrate and kill cells within the structure. Several targets have been identified, ranging from the inhibition of quorum sensing receptors and virulence factors, to cell wall synthesizing enzymes. Only one group of these fungal metabolites has been optimized and made it to the market, but more preclinical studies are ongoing to expand the biofilm-fighting arsenal. The broad diversity of bioactive compounds from fungi, their activities against various pathogens, and the multi-target trait of some molecules are promising aspects of fungal secondary metabolites. Future screenings for biofilm-controlling compounds will contribute to several novel clinical applications.

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Effect of caspofungin and micafungin in combination with farnesol against Candida parapsilosis biofilms

Cited by 50 publications

References 29 publications

Candida biofilm production is associated with higher mortality in patients with candidaemia

Candida biofilm production is associated with higher mortality in patients with candidaemia

Synergistic effect of nikkomycin Z with caspofungin and micafungin against Candida albicans and Candida parapsilosis biofilms

Fungal Metabolites for the Control of Biofilm Infections

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