Nitroglycerin-Citrate-Ethanol Catheter Lock Solution Is Highly Effective for
            <i>In Vitro</i>
            Eradication of Candida auris Biofilm

Vargas-Cruz, Nylev; Reitzel, Ruth; Rosenblatt, Joel; Chaftari, Anne-Marie; Dib, Rita Wilson; Hachem, Ray; Kontoyiannis, Dimitrios P.; Raad, Issam

doi:10.1128/aac.00299-19

Cited by 16 publications

(14 citation statements)

References 21 publications

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“…On the other hand, nitric oxide (NO), a natural product of the immune system, acts as a broad-spectrum antimicrobial agent. In fungi, the NO has shown efficacy against C. auris [12,101]. Cleare et al, 2020 demonstrated the effectiveness of NO nanoparticles (NAC-SNO-np) against six C. auris clinical isolates.…”

Section: Alternative Treatment Strategies In C Aurismentioning

confidence: 99%

Antifungal Resistance in Candida auris: Molecular Determinants

et al. 2020

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Since Candida auris integrates strains resistant to multiple antifungals, research has been conducted focused on knowing which molecular mechanisms are involved. This review aims to summarize the results obtained in some of these studies. A search was carried out by consulting websites and online databases. The analysis indicates that most C. auris strains show higher resistance to fluconazole, followed by amphotericin B, and less resistance to 5-fluorocytosine and caspofungin. In C. auris, antifungal resistance to amphotericin B has been linked to an overexpression of several mutated ERG genes that lead to reduced ergosterol levels; fluconazole resistance is mostly explained by mutations identified in the ERG11 gene, as well as a higher number of copies of this gene and the overexpression of efflux pumps. For 5-fluorocytosine, it is hypothesized that the resistance is due to mutations in the FCY2, FCY1, and FUR1 genes. Resistance to caspofungin has been associated with a mutation in the FKS1 gene. Finally, resistance to each antifungal is closely related to the type of clade to which the strain belongs.

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Section: Alternative Treatment Strategies In C Aurismentioning

confidence: 99%

Antifungal Resistance in Candida auris: Molecular Determinants

et al. 2020

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“…Although there is increasing recognition that antibiotic lock solutions can reduce the risk of catheter-related bacterial infections, there is no approved antifungal lock therapeutic protocol in clinical practice so far. Vargas-Cruz et al (2019) reported that liposomal amphotericin B, amphotericin B deoxycholate, fluconazole, voriconazole, micafungin, caspofungin, and anidulafungin failed to completely eradicate C. auris biofilms, contraindicating their mono-therapeutic use in lock therapy [ 23 ]. Therefore, certain non-antifungal agents alone or in combination with traditional antifungals have been investigated as a potential approach to overcome C. auris -related catheter-associated infections.…”

Section: Discussionmentioning

confidence: 99%

“…Taurolidine showed moderate activity against biofilms and only partially eradicated sessile populations. Conversely, the minocycline-EDTA-ethanol lock solution and nitroglycerin-citrate-ethanol combination completely eradicated C. auris biofilms in vitro [ 23 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

The Neosartorya fischeri Antifungal Protein 2 (NFAP2): A New Potential Weapon against Multidrug-Resistant Candida auris Biofilms

Kovács

Nagy

Tóth

et al. 2021

IJMS

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Candida auris is a potential multidrug-resistant pathogen able to persist on indwelling devices as a biofilm, which serve as a source of catheter-associated infections. Neosartorya fischeri antifungal protein 2 (NFAP2) is a cysteine-rich, cationic protein with potent anti-Candida activity. We studied the in vitro activity of NFAP2 alone and in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin against C. auris biofilms. The nature of interactions was assessed utilizing the fractional inhibitory concentration index (FICI), a Bliss independence model, and LIVE/DEAD viability assay. NFAP2 exerted synergy with all tested antifungals with FICIs ranging between 0.312–0.5, 0.155–0.5, 0.037–0.375, 0.064–0.375, and 0.064–0.375 for fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. These results were confirmed using a Bliss model, where NFAP2 produced 17.54 μM2%, 2.16 μM2%, 33.31 μM2%, 10.72 μM2%, and 111.19 μM2% cumulative synergy log volume in combination with fluconazole, amphotericin B, anidulafungin, caspofungin, and micafungin, respectively. In addition, biofilms exposed to echinocandins (32 mg/L) showed significant cell death in the presence of NFAP2 (128 mg/L). Our study shows that NFAP2 displays strong potential as a novel antifungal compound in alternative therapies to combat C. auris biofilms.

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“…The multidrug resistance phenotype is a well-known characteristic for C. auris; it may be more pronounced in biofilms and further complicate treatment [6]. Based on previous susceptibility testing, amphotericin B, fluconazole, voriconazole, anidulafungin, micafungin and caspofungin could not completely eradicate C. auris biofilms in vitro, increasing the need for effective combination therapies [39]. Certain non-antifungal agents in combination with traditional antifungal drugs have been tested to eradicate C. auris biofilms with variable efficacy [21,22,40].…”

Section: Discussionmentioning

confidence: 99%

In vitroandin vivointeraction of caspofungin with isavuconazole againstCandida aurisplanktonic cells and biofilms

Nagy

Tóth

Nyikos

et al. 2021

Preprint

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The in vitro and in vivo efficacy of caspofungin was determined in combination with isavuconazole against Candida auris. Drug-drug interactions were assessed utilising the fractional inhibitory concentration indices (FICIs), the Bliss independence model and an immunocompromised mouse model. Median planktonic minimum inhibitory concentrations (pMICs) of 23 C. auris isolates were between 0.5 and 2 mg/L and between 0.015 and 4 mg/L for caspofungin and isavuconazole, respectively. Median pMICs for caspofungin and isavuconazole in combination showed 2-128-fold and 2-256-fold decreases, respectively. Caspofungin and isavuconazole showed synergism in 14 out of 23 planktonic isolates (FICI range 0.03-0.5; Bliss cumulative synergy volume range 0-4.83). Median sessile MICs (sMIC) of 14 biofilm-forming isolates were between 32 and >32 mg/L and between 0.5 and >2 mg/L for caspofungin and isavuconazole, respectively. Median sMICs for caspofungin and isavuconazole in combination showed 0-128-fold and 0-512-fold decreases, respectively. Caspofungin and isavuconazole showed synergistic interaction in 12 out of 14 sessile isolates (FICI range 0.023-0.5; Bliss cumulative synergy volume range 0.13-234.32). In line with the in vitro findings, synergistic interactions were confirmed by in vivo experiments. The fungal kidney burden decreases were more than 3 log volumes in mice treated with combination of 1 mg/kg caspofungin and 20 mg/kg isavuconazole daily; this difference was statistically significant compared with control mice (p<0.001). Despite the favourable effect of isavuconazole in combination with caspofungin, further studies are needed to confirm the therapeutic advantage of this combination when treating an infection caused by C. auris.

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Nitroglycerin-Citrate-Ethanol Catheter Lock Solution Is Highly Effective for In Vitro Eradication of Candida auris Biofilm

Cited by 16 publications

References 21 publications

Antifungal Resistance in Candida auris: Molecular Determinants

Antifungal Resistance in Candida auris: Molecular Determinants

The Neosartorya fischeri Antifungal Protein 2 (NFAP2): A New Potential Weapon against Multidrug-Resistant Candida auris Biofilms

In vitroandin vivointeraction of caspofungin with isavuconazole againstCandida aurisplanktonic cells and biofilms

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