Dataset Information

PCR-detectable Candida DNA exists a short period in the blood of systemic candidiasis murine model.

ABSTRACT: Invasive candidiasis is a major challenge to clinical medicine today. However, traditional fungal diagnostic techniques and empirical treatments have shown great limitations. Although efforts are necessarily needed in methodology standardization and multicenter validation, polymerase chain reaction (PCR) is a very promising assay in detecting fungal pathogens. Using a "heat-shock" DNA preparation method, a rapid and simple PCR protocol for quantification of the Candida albicans (C. albicans) ribosomal DNA was established. The PCR assay could detect Candida DNA as low as 10 CFU/mL in samples prepared by the heat-shock protocol, without any cross-reaction with DNA prepared from other Candida spp. and bacterial pathogens. For simulated blood samples, the PCR test sensitivity of whole blood samples was better than that of plasma and blood cells. In the systemic candidiasis murine model, detectable DNA was only observed within 24 h after C. albicans SC5314 injection, which is much shorter than that observed in the kidney.

SUBMITTER: He ZX

PROVIDER: S-EPMC7747513 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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PCR-detectable Candida DNA exists a short period in the blood of systemic candidiasis murine model.

He Zheng-Xin ZX Zhao Hui-Hai HH Wang Fu-Kun FK

Open life sciences 20200906 1

Invasive candidiasis is a major challenge to clinical medicine today. However, traditional fungal diagnostic techniques and empirical treatments have shown great limitations. Although efforts are necessarily needed in methodology standardization and multicenter validation, polymerase chain reaction (PCR) is a very promising assay in detecting fungal pathogens. Using a "heat-shock" DNA preparation method, a rapid and simple PCR protocol for quantification of the Candida albicans (C. alb ...[more]

PMID: 33817256

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Project description:Pharmacodynamic (PD) studies with triazoles in the neutropenic murine disseminated candidiasis model have been performed extensively for Candida albicans. They have consistently shown that the pharmacodynamic index most closely correlated with efficacy is the ratio of the 24-h area under the concentration-time curve (AUC) to the MIC, and a target 24-h free-drug AUC/MIC ratio near 25 is associated with 50% of maximal microbiologic efficacy. We utilized this model to investigate the pharmacodynamics of isavuconazole. Isavuconazole pharmacokinetics were linear over the dose range studied. Oral-gastric doses of 640, 160, 40, and 10 mg of prodrug/kg of body weight produced peak levels of 0.51 to 25.4 mg/liter, an elimination half-life of 1 to 5 h, and an AUC from 0 h to infinity (AUC0-∞) of 0.9 to 287 mg · h/liter. The AUC/MIC ratio was the pharmacodynamic index that correlated best with efficacy (R(2), 0.84). Pharmacodynamic target studies were performed using 4 C. albicans isolates with both a 24-h and a 96-h treatment duration. The strains were chosen to include previously characterized fluconazole-resistant strains. The mean 50% effective doses (ED50) (expressed in mg/kg of body weight/12 h) and associated 24-h free-drug AUC/MIC ratios were 89.3 ± 46.7 and 67.7 ± 35 for the 24-h treatment and 59.6 ± 22 and 33.3 ± 25.5 for the 96-h treatment. These differences were not statistically significant. Pharmacodynamic targets for two non-albicans Candida species were also explored. The mean ED50 (expressed in mg/kg/12 h) and associated 24-h free-drug AUC/MIC ratios were 31.2 and 6.2 for Candida tropicalis (n = 1) and 50.5 and 1.6 for Candida glabrata (n = 2). These PD targets were significantly different from C. albicans targets (P, 0.04). Isavuconazole PD targets for C. albicans are similar to those observed in this model with other triazoles. However, the PD targets for non-albicans Candida species were more than 10-fold lower than those for C. albicans (P, 0.04). This difference is similar to the species-specific PD relationships for the echinocandins. The lower PD targets for these species in this model will be important to consider in the analysis of clinical trial data and during the development of susceptibility breakpoints.

Dataset Information

PCR-detectable Candida DNA exists a short period in the blood of systemic candidiasis murine model.

Publications

PCR-detectable <i>Candida</i> DNA exists a short period in the blood of systemic candidiasis murine model.

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