Candidaemia associated with decreased in vitro fluconazole susceptibility: is Candida speciation predictive of the susceptibility pattern?

Oxman, David; Chow, Jennifer; Frendl, György; Hadley, Susan; Hershkovitz, Shay; Ireland, Peter T.; McDermott, L. A.; Tsai, Katy K.; Marty, Francisco M.; Kontoyiannis, Dimitrios P.; Golan, Yoav

doi:10.1093/jac/dkq136

Cited by 87 publications

(90 citation statements)

References 23 publications

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“…These results were confirmed by the SEM images of CgS (Figure 10(D,E)) and CgR (Figure 11(D,E)), which showed that fewer cells and cell agglomerates were more sparsely distributed on the substrate. It has been reported that C. glabrata has a decreased intrinsic susceptibility to FLZ and other classes of azole antifungals [42,50,51]. Nevertheless, the results of the present study showed that biofilm formation with 40 µg/mL of FLZ for CgS and 1,280 µg/mL of FLZ for CgR can reduce the cell viability of these microorganisms.…”

Section: Discussioncontrasting

confidence: 75%

Fluconazole impacts the extracellular matrix of fluconazole-susceptible and -resistant Candida albicans and Candida glabrata biofilms

Panariello

Klein

Mima

et al. 2018

Journal of Oral Microbiology

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Background: Fluconazole (FLZ) is a drug commonly used for the treatment of Candida infections. However, β-glucans in the extracellular matrices (ECMs) hinder FLZ penetration into Candida biofilms, while extracellular DNA (eDNA) contributes to the biofilm architecture and resistance. Methods: This study characterized biofilms of FLZ-sensitive (S) and -resistant (R) Candida albicans and Candida glabrata in the presence or absence of FLZ focusing on the ECM traits. Biofilms of C. albicans American Type Culture Collection (ATCC) 90028 (CaS), C. albicans ATCC 96901 (CaR), C. glabrata ATCC 2001 (CgS), and C. glabrata ATCC 200918 (CgR) were grown in RPMI medium with or without FLZ at 5× the minimum inhibitory concentration (37°C/48 h). Biofilms were assessed by colony-forming unit (CFU)/mL, biomass, and ECM components (alkali-soluble polysaccharides [ASP], water-soluble polysaccharides [WSP], eDNA, and proteins). Scanning electron microscopy (SEM) was also performed. Data were analyzed by parametric and nonparametric tests (α = 0.05). Results: In biofilms, FLZ reduced the CFU/mL of all strains (p < 0.001), except for CaS (p = 0.937). However, the ASP quantity in CaS was significantly reduced by FLZ (p = 0.034), while the drug had no effect on the ASP levels in other strains (p > 0.05). Total biomasses and WSP were significantly reduced by FLZ in the ECM of all yeasts (p < 0.001), but levels of eDNA and proteins were unaffected (p > 0.05). FLZ affected the cell morphology and biofilm structure by hindering hyphae formation in CaS and CaR biofilms, by decreasing the number of cells in CgS and CgR biofilms, and by yielding sparsely spaced cell agglomerates on the substrate. Conclusion: FLZ impacts biofilms of C. albicans and C. glabrata as evident by reduced biomass. This reduced biomass coincided with lowered cell numbers and quantity of WSPs. Hyphal production by C. albicans was also reduced.

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Section: Discussioncontrasting

confidence: 75%

Fluconazole impacts the extracellular matrix of fluconazole-susceptible and -resistant Candida albicans and Candida glabrata biofilms

Panariello

Klein

Mima

et al. 2018

Journal of Oral Microbiology

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“…For instance, C. glabrata is inherently less susceptible to fluconazole. In addition, the emergence of fluconazole resistance has been reported in species typically susceptible to this agent, such as C. albicans, Candida tropicalis and Candida parapsilosis (Hajjeh et al, 2004;Yang et al, 2004;Lyon et al, 2010;Oxman et al, 2010;Arendrup et al, 2011), including that observed in Brazilian tertiarycare hospitals (Bruder-Nascimento et al, 2010;Favalessa et al, 2010;Pereira et al, 2010;Furlaneto et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

In vitro antifungal activity of the flavonoid baicalein against Candida species

Serpa

França

Furlaneto-Maia

et al. 2012

Journal of Medical Microbiology

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The aim of the present study was to evaluate the in vitro activity of baicalein, the flavone constituent of Scutellaria baicalensis, and synergism of the combination of baicalein and fluconazole against Candida albicans, Candida tropicalis and Candida parapsilosis. The MIC 50 (lowest concentration at which there was 50 % inhibition of growth) of baicalein alone against six Candida strains ranged from 13 to 104 mg ml "1 . For the three species tested, exposure to baicalein at the MIC 50 concentrations obtained for each strain resulted in a high loss of viability. The fluconazole plus baicalein combination markedly reduced the MICs of both drugs for all three strains analysed. In addition, a synergistic effect between baicalein and fluconazole was observed for C. parapsilosis in terms of MIC 50 (fractional inhibitory concentration index50.207). Scanning electron microscopy analysis revealed that yeast cells exposed to baicalein at MIC 50 produced a profusely flocculent extracellular material, resembling a biofilm-like structure. In conclusion, these results showed the antifungal capability of baicalein against Candida species and highlight a promising role of baicalein when used in combination with fluconazole against Candida infections. INTRODUCTIONCandidiasis is one of the most common fungal infections in humans caused by Candida species, most notably by Candida albicans. Currently, other species of this genus have been found to cause an increasing number of cases of candidiasis (Mokaddas et al., 2007;Pereira et al., 2010;Das et al., 2011).The therapy of invasive candidiasis remains a difficult medical problem. Despite the availability of extendedspectrum triazoles, the incidence of invasive infections and resistance to antifungal therapy continue to increase (Pfaller & Diekema, 2010). Widespread use of antifungal agents could be an explanation for the emergence of the more resistant non-albicans species of Candida, such as Candida glabrata (reviewed by Kothavade et al., 2010; Silva et al., 2012).The azole fluconazole is effective against most Candida species and is used currently as a first-line drug, although different degrees of susceptibility among species have been described. For instance, C. glabrata is inherently less susceptible to fluconazole. In addition, the emergence of fluconazole resistance has been reported in species typically susceptible to this agent, such as C. albicans, Candida tropicalis and Candida parapsilosis (Hajjeh et al., 2004;Yang et al., 2004;Lyon et al., 2010;Oxman et al., 2010; Arendrup et al., 2011), including that observed in Brazilian tertiarycare hospitals (Bruder-Nascimento et al., 2010;Favalessa et al., 2010;Pereira et al., 2010;Furlaneto et al., 2011).These factors present an urgent need to search for novel compounds with anticandidal activity. To this end, efforts have been made in the search for novel antifungal agents from various natural sources. In this regard, baicalein (5,6,7-trihydroxyflavone; Fig. 1) is a flavonoid originally isolated from the roots of the Chine...

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“…Voriconazole and itraconazole may also be employed as alternative therapies to treat cases of candidaemia (Pappas et al, 2009 demonstrates less in vitro susceptibility than other Candida members, although the clinical relevance is still uncertain (Gleason et al, 1997;Rocco et al, 2000;Lopez et al, 2001;Rex et al, 2001;da Matta et al, 2007;Pappas et al 2009;Arendrup, 2010). Some species that are generally considered fully susceptible to fluconazole may include subpopulations with reduced susceptibility (Oxman et al, 2010). Additionally, newly described cryptic species, as seen in the C. parapsilosis group, have presented distinct drug susceptibility patterns (Lockhart et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Prevalence, distribution and antifungal susceptibility profiles of Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis bloodstream isolates

Bonfietti

Martins

Szeszs

et al. 2012

Journal of Medical Microbiology

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Candidaemia associated with decreased in vitro fluconazole susceptibility: is Candida speciation predictive of the susceptibility pattern?

Cited by 87 publications

References 23 publications

Fluconazole impacts the extracellular matrix of fluconazole-susceptible and -resistant Candida albicans and Candida glabrata biofilms

Fluconazole impacts the extracellular matrix of fluconazole-susceptible and -resistant Candida albicans and Candida glabrata biofilms

In vitro antifungal activity of the flavonoid baicalein against Candida species

Prevalence, distribution and antifungal susceptibility profiles of Candida parapsilosis, Candida orthopsilosis and Candida metapsilosis bloodstream isolates

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