Voriconazole minimum inhibitory concentrations are predictive of treatment outcome in experimental murine infections by Candida glabrata

Silva, Marta; Capilla, Javier; Castanheira, Mariana; Martín‐Vicente, Adela; Sutton, Deanna A.; Fothergill, Annette W.; Wiederhold, Nathan P.; Guarro, Josep

doi:10.1016/j.ijantimicag.2015.12.020

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…In our study, the activities of VCZ and PCZ against these three Candida strains were similar; both drugs achieved a similar increase in worm survival percentage in each Candida strain infection. In vivo studies conducted in murine models also exhibited the same improvement for both antifungal drugs against C. glabrata infection (46,47). In vitro susceptibility of C. glabrata and C. bracarensis to these broad-spectrum triazoles has been reported, although reduced susceptibility of C. glabrata (5,48) and C. bracarensis (24,32) isolates has also been described.…”

Section: Discussionmentioning

confidence: 72%

Caenorhabditis elegans as a Model System To Assess Candida glabrata, Candida nivariensis , and Candida bracarensis Virulence and Antifungal Efficacy

Hernando-Ortiz

Mateo

Ortega-Riveros

et al. 2020

Antimicrob Agents Chemother

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Although Candida albicans remains the major etiological agent of invasive candidiasis, Candida glabrata and other emerging species of Candida are increasingly isolated. This species is the second most prevalent cause of candidiasis in many regions of the world. However, clinical isolates of Candida nivariensis and Candida bracarensis can be misidentified and are underdiagnosed due to shared phenotypic traits with C. glabrata. Little is known about both cryptic species. Pathogenesis studies are therefore needed to understand their virulence traits and their susceptibility to antifungal drugs. The susceptibility of Caenorhabditis elegans to different Candida species makes this nematode an excellent model for assessing host–fungal interactions. We evaluated the usefulness of C. elegans as a nonconventional host model to analyze the virulence of C. glabrata, C. nivariensis and C. bracarensis. The three species caused candidiasis and the highest virulence of C. glabrata was confirmed. Furthermore, we determined the efficacy of current antifungal drugs against the infection caused by these species in the C. elegans model. Amphotericin B and azoles showed the highest activity against C. glabrata and C. bracarensis infections, while echinocandins were more active for treating those caused by C. nivariensis. C. elegans proved to be a useful model system for assessing the pathogenicity of these closely related species.

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Section: Discussionmentioning

confidence: 72%

Caenorhabditis elegans as a Model System To Assess Candida glabrata, Candida nivariensis , and Candida bracarensis Virulence and Antifungal Efficacy

Hernando-Ortiz

Mateo

Ortega-Riveros

et al. 2020

Antimicrob Agents Chemother

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“…Previous animal studies showed that voriconazole at 40 mg/kg once daily was effective at reducing statistically significantly kidney fungal burden >1 log 10 cfu/g (average $2 log 10 cfu/g) compared with untreated controls after 7 days of treatment against C. glabrata isolates with CLSI MICs of 0.125 mg/L in grapefruit-fed neutropenic mice. 23 In vitro PK/PD relationship for C. glabrata Beredaki et al…”

Section: Discussionmentioning

confidence: 99%

Voriconazole efficacy against Candida glabrata and Candida krusei: preclinical data using a validated in vitro pharmacokinetic/pharmacodynamic model

Beredaki

Georgiou

Siopi

et al. 2019

Journal of Antimicrobial Chemotherapy

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Background Voriconazole exhibits in vitro activity against Candida glabrata and Candida krusei (EUCAST/CLSI epidemiological cut-off values 1/0.25 and 1/0.5 mg/L, respectively). Yet, EUCAST found insufficient evidence to set breakpoints for these species. We explored voriconazole pharmacodynamics (PD) in an in vitro dynamic model simulating human pharmacokinetics (PK). Methods Four C. glabrata and three C. krusei isolates (voriconazole EUCAST and CLSI MICs of 0.03–2 mg/L) were tested in the PK/PD model simulating voriconazole exposures (t½ ∼6 h q12h dosing for 3 days). PK/PD breakpoints were determined calculating the PTA for exposure indices fAUC0–24/MIC associated with half-maximal activity (EI50) using Monte Carlo simulation analysis. Results Fungal load increased from 3.60 ± 0.35 to 8.41 ± 0.24 log10 cfu/mL in the drug-free control, with a maximum effect of ∼1 log10 kill of C. glabrata and C. krusei isolates with MICs of 0.06 and 0.25 mg/L, respectively, at high drug exposures. The 72 h log10 cfu/mL change versus fAUC0–24/MIC relationship followed a sigmoid curve for C. glabrata (R2=0.85–0.87) and C. krusei (R2=0.56–0.76) with EI50 of 49 (32–76) and 52 (33–78) fAUC/MIC for EUCAST and 55 (31–96) and 80 (42–152) fAUC/MIC for CLSI, respectively. The PTAs for C. glabrata and C. krusei isolates with EUCAST/CLSI MICs ≤0.125/≤0.06 mg/L were >95%. Isolates with EUCAST/CLSI MICs of 0.25–1/0.125–0.5 would require trough levels 1–4 mg/L; isolates with higher MICs would not attain the corresponding PK/PD targets without reaching toxicity. Conclusions The in vitro PK/PD breakpoints for C. glabrata and C. krusei for EUCAST (0.125 mg/L) and CLSI (0.06 mg/L) bisected the WT populations. Trough levels of >4 mg/L, which are not clinically feasible, are necessary for efficacy against WT isolates.

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“…For example, fungi need simple nutritional requirements, easy to get, have great wallbinding size, and high absorption capabilities (24). The Penicillium chrysogenum is characterized by being fast growing on the medium and has the importance of being an antimicrobial, so it was used for the biosynthesis of silver nanoparticles (23). Mice are widely-used in laboratory experiments as animal models, where we can diagnose different types of clinical Candida (2,26).…”

Section: Intruductionmentioning

confidence: 99%

A COMET ASSAY FOR CANDIDA GLABRATA INFECTION AND TREATMENT BY PENICILLIUM CHRYSOGENUM - DERIVED AgNPs

Teeba H. Mohammad

2023

Iraqi J. Agric. Sci.

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The colonies of C. glabrata were described, which morphology of isolated on sabouraud dextrose agar with chloramphenicol. Biosynthesis of nanoparticles is of great importance since they are highly involved in various medical and biological applications. The current study aims to produce Penicillium chrysogenum - derived AgNPs to be used to treat Candida glabrata. Nanoparticles were formed, the results of which was observed through UV-visible spectrophotometry. Therefore, the surface morphology and particles size of AgNPs were assessed using the scanning electron microscope (SEM). The atomic force microscopy (AFM) confirmed that the average diameter of AgNPs was 18 nm which is appropriate to be used to deliver Penicillium chrysogenum to the Candida infected cells. The antifungal activity of AgNPs against C. glabrata was investigated in the serum of 15 mice. The mice were divided into four groups was examined after 21 days. A comet assay described procedure that sensitive measurement and permits reproducible of DNA repair and DNA damage using C. glabrara infection and treatment by Penicillium chrysogenum - derived AgNPs. This combination of assay with affected C. glabrara in DNA repaired and the extensive range of obtainable fungal molecular biology apparatuses can donate to light important devices of genome.

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Voriconazole minimum inhibitory concentrations are predictive of treatment outcome in experimental murine infections by Candida glabrata

Cited by 5 publications

References 24 publications

Caenorhabditis elegans as a Model System To Assess Candida glabrata, Candida nivariensis , and Candida bracarensis Virulence and Antifungal Efficacy

Caenorhabditis elegans as a Model System To Assess Candida glabrata, Candida nivariensis , and Candida bracarensis Virulence and Antifungal Efficacy

Voriconazole efficacy against Candida glabrata and Candida krusei: preclinical data using a validated in vitro pharmacokinetic/pharmacodynamic model

A COMET ASSAY FOR CANDIDA GLABRATA INFECTION AND TREATMENT BY PENICILLIUM CHRYSOGENUM - DERIVED AgNPs

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