scholarly journals Farnesol increases the activity of echinocandins against Candida auris biofilms

2019 ◽  
Vol 58 (3) ◽  
pp. 404-407 ◽  
Author(s):  
Fruzsina Nagy ◽  
Zoltán Tóth ◽  
Lajos Daróczi ◽  
Adrien Székely ◽  
Andrew M Borman ◽  
...  

Abstract Candida auris biofilms exhibit decreased susceptibility to echinocandins, which is associated with poorer clinical outcomes. Farnesol is a quorum-sensing molecule enhancing the activity of antifungals; therefore, we evaluated the in vitro effect of farnesol with anidulafungin, caspofungin, or micafungin against biofilms using fractional inhibitory concentration indexes (FICI), Bliss independence model, LIVE/DEAD-assay and scanning electron microscopy. Based on mathematical models, farnesol caused synergism in eleven out of twelve cases (FICIs range 0.133-0.507; Bliss synergy volume range 70.39–204.6 μM2%). This was confirmed by microscope images of combination-exposed biofilms. Our study showed the prominent effect of farnesol with echinocandins against C. auris biofilms.

Author(s):  
Fruzsina Nagy ◽  
Zoltán Tóth ◽  
Fanni Nyikos ◽  
Lajos Forgács ◽  
Ágnes Jakab ◽  
...  

AbstractThe 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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Patrick Schwarz ◽  
Anne-Laure Bidaud ◽  
Eric Dannaoui

AbstractThe in vitro interactions of isavuconazole with colistin were evaluated against 15 clinical Candida auris isolates by a microdilution checkerboard technique based on the EUCAST reference method for antifungal susceptibility testing and by agar diffusion using isavuconazole gradient concentration strips with or without colistin incorporated RPMI agar. Interpretation of the checkerboard results was done by the fractional inhibitory concentration index and by response surface analysis based on the Bliss model. By checkerboard, combination was synergistic for 93% of the isolates when interpretation of the data was done by fractional inhibitory concentration index, and for 80% of the isolates by response surface analysis interpretation. By agar diffusion test, although all MICs in combination decreased compared to isavuconazole alone, only 13% of the isolates met the definition of synergy. Essential agreement of EUCAST and gradient concentration strip MICs at +/− 2 log2 dilutions was 93.3%. Antagonistic interactions were never observed for any technique or interpretation model used.


2011 ◽  
Vol 35 (1) ◽  
pp. 115-123 ◽  
Author(s):  
Ricardo Borges Pereira ◽  
Gilvaine Ciavareli Lucas ◽  
Fabiano José Perina ◽  
Mário Lúcio Vilela de Resende ◽  
Eduardo Alves

The objectives of this work were to assess the in vitro effect of essential oils extracted from cinnamon, citronella, lemon grass, India clove, tea tree, thyme, neem and eucalyptus on the conidia germination and on mycelial growth of Cercospora coffeicola, and their efficacy to control the brown eye spot in coffee seedlings (cultivars Catucaí 2SL, Catuaí IAC 62 and Mundo Novo 379/19) in a greenhouse, as well as their effects on the initial germination and infection events by scanning electron microscopy. All essential oils promoted the inhibition of conidia germination with increasing concentrations. India clove, cinnamon, neem, thyme and lemon grass oils inhibited the mycelial growth of C. coffeicola. The cinnamon and citronella oils were the most promising for brown eye spot control in all cultivars. In scanning electron microscopy, the cinnamon and citronella oils reduced germination and mycelial development of C. coffeicola in vivo, eight and 16 hours after inoculation, promoting, in some cases, the leakage of the cellular content. Essential oils of cinnamon and citronella reduced the incidence and severity of brown eye spot, in addition to presenting direct toxicity to the pathogen.


2019 ◽  
Vol 63 (12) ◽  
Author(s):  
A. L. Bidaud ◽  
F. Botterel ◽  
A. Chowdhary ◽  
E. Dannaoui

ABSTRACT Candida auris is an emerging, multidrug-resistant pathogen responsible for invasive hospital-acquired infections. Flucytosine is an effective anti-Candida species drug, but which cannot be used as a monotherapy because of the risk of development of resistant mutants during treatment. It is, therefore, noteworthy to test possible combinations with flucytosine that may have a synergistic interaction. In this study, we determined the in vitro interaction between flucytosine and amphotericin B, micafungin, or voriconazole. These combinations have been tested against 15 C. auris isolates. The MIC ranges (geometric mean [Gmean]) of flucytosine, amphotericin B, micafungin, and voriconazole were 0.125 to 1 μg/ml (0.42 μg/ml), 0.25 to 1 μg/ml (0.66 μg/ml), 0.125 to 0.5 μg/ml (0.3 μg/ml), and 0.03 to 4 μg/ml (1.05 μg/ml), respectively. When tested in combination, indifferent interactions were mostly observed with fractional inhibitory concentration index values from 0.5 to 1, 0.31 to 1.01, and 0.5 to 1.06 for the combinations of flucytosine with amphotericin B, micafungin, and voriconazole, respectively. A synergy was observed for the strain CBS 10913 from Japan. No antagonism was observed for any combination. The combination of flucytosine with amphotericin B or micafungin may be relevant for the treatment of C. auris infections.


2020 ◽  
Vol 7 (4) ◽  
pp. 154
Author(s):  
Giovanni Cilia ◽  
Filippo Fratini ◽  
Elena della Buona ◽  
Fabrizio Bertelloni

Environmental resistance is an important factor for understanding the epidemiology of leptospirosis. Recently, new Leptospira hosts were identified, including also marine mammals. Moreover, halotolerant Leptospira strain, isolated from the environment and animals, highlighted the capability of this microorganism to persist in the seawater. The aim of this research was to investigate the bacteriostatic and bactericidal effect of salt on Leptospira strains belonging to 16 different serovars. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were verified through the microdilutions method starting from a 20% sodium chloride concentration. MIC values obtained were between 0.3125% and 10% of salt, while MBC values between 0.625% and >20%. Icterohaemorrhagiae (MIC: 0.3125%; MBC: 0.625%) resulted the most inhibited serovar, while the most resistant was Tarassovi (MIC: 10%; MBC: >20%). Interestingly, trends were reported for Pomona (MIC: 1.25%; MBC: >20%) and Bratislava (MIC: 0.625%; MBC: 20%), highlighting low MIC values but high MBC values. This is the first investigation aimed at the in vitro effect of salt on the growth of Leptospira spp. reference strains.


Materials ◽  
2019 ◽  
Vol 12 (9) ◽  
pp. 1401 ◽  
Author(s):  
Liza L. Ramenzoni ◽  
Thomas Attin ◽  
Patrick R. Schmidlin

Improving soft tissue attachment to implant abutments is a crucial factor for enduring health and maintenance of soft peri-implant tissue health. In this in vitro study we aimed to compare the biocompatibility of three different abutment surfaces: titanium, zirconia and modified polyetheretherketone (PEEK). Surface topography, roughness and wettability were investigated with scanning electron microscopy, profilometer and contact angle meter, respectively. Human gingival epithelial keratinocytes were examined for viability, morphology, proliferation and migration by using tetrazolium salt colorimetric assay, scanning electron microscopy imaging, immunofluorescence bromodeoxyuridine analysis and scratch wound healing assays. Roughness measurements revealed differences between the investigated surfaces. Keratinocytes cultured on all examined surfaces indicated adhesion and attachment by means of scanning electron microscopy imaging. Cell viability assays showed no significant differences between the groups (p > 0.05). The modified PEEK surface similarly improved surface roughness in comparison to titanium and zirconia, which resulted in greater and equivalent cell proliferation and migration. The study methodology showed here may emphasize the importance of cell interactions with different abutment materials, which in part increases the changes of implant success. PEEK, titanium and zirconia surface types used in this study showed mostly similar epithelial biological responses.


2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Hamed Fakhim ◽  
Anuradha Chowdhary ◽  
Anupam Prakash ◽  
Afsane Vaezi ◽  
Eric Dannaoui ◽  
...  

ABSTRACT We determined the in vitro interactions between echinocandins and azoles against 10 multidrug-resistant Candida auris strains by use of a microdilution checkerboard technique. Our results suggest synergistic interactions between micafungin and voriconazole with fractional inhibitory concentration index (FICI) values of 0.15 to 0.5, and we observed indifferent interactions when micafungin was combined with fluconazole (FICI, 0.62 to 1.5). Combinations of caspofungin with fluconazole or voriconazole exhibited indifferent interactions. No antagonism was observed for any combination.


2016 ◽  
Vol 60 (4) ◽  
pp. 2346-2351 ◽  
Author(s):  
S. Deng ◽  
W. Pan ◽  
W. Liao ◽  
G. S. de Hoog ◽  
A. H. G. Gerrits van den Ende ◽  
...  

ABSTRACTPrimary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungiCladophialophora bantiana,Rhinocladiella mackenziei, andExophiala dermatitidis.Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Ourin vitrostudies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum ΔE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the orderChaetothyriales. Furtherin vivostudies and clinical investigations to elucidate and confirm these observations are warranted.


2021 ◽  
Vol 22 (2) ◽  
pp. 771
Author(s):  
Renátó Kovács ◽  
Fruzsina Nagy ◽  
Zoltán Tóth ◽  
Lajos Forgács ◽  
Liliána Tóth ◽  
...  

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.


Author(s):  
R. Kannan ◽  
V. Dhivya

Background: Mango productivity was very much affected due to a major fungal pathogen, Colletotrichum gloeosporioides causing anthracnose mango rot. The present study was carried out to investigate the influence of abiotic factors for the support of superficial growth of isolated fungus and finding a minimum inhibitory concentration of different fungicides. Methods: Among four different culture media tested, the highest radial growth and sporulation of the fungus were recorded in Oatmeal agar (OMA) (84 mm) followed by Conn’s agar (CA), Czapek Dox agar (CDA) and Potato dextrose agar (PDA). Among the different pH tested, pH 7.0 was found to be the best in supporting the good radial growth (69 mm) followed by pH 6.0 (56 mm), pH 5.5 (49 mm), pH 7.5 (43 mm) and pH 8.0 (37 mm). Among the various temperature tested, 25oC (69.32) was found to be the best followed by 20oC (52.53 mm), 30oC (65.23 mm) and 35oC. Result: Among the fungicides tested, Zineb 68% + Hexaconazole 4% WP (avtar) was found best as the radial growth was observed to be 45, 41, 36, 32, 25 mm at 5, 10, 25, 50 and 100 ppm, respectively as compared to 80 mm in control. The fungicide Tricyclazole 18% + Mancozeb 62% WP (Merger) was found to be the least effective in checking the radial growth of C. gloeosporioides even at 100 ppm concentration.


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