Invasive fungal infections in patients with cancer in the Intensive Care Unit.
ABSTRACT Invasive fungal infections (IFIs) have emerged as a major cause of morbidity and mortality amongst critically ill patients. Cancer patients admitted to the Intensive Care Unit (ICU) have multiple risk factors for IFIs. The vast majority of IFIs in the ICU are due to Candida spp. The incidence of invasive candidiasis (IC) has increased over recent decades, especially in the ICU. A shift in the distribution of Candida spp. from Candida albicans to non-albicans Candida spp. has been observed both in ICUs and oncology units in the last two decades. Timely diagnosis of IC remains a challenge despite the introduction of new microbiology techniques. Delayed initiation of antifungal therapy is associated with increased mortality. Therefore, prediction rules have been developed and validated prospectively in order to identify those ICU patients at high risk for IC and likely to benefit from early treatment. These rules, however, have not been validated in cancer patients. Similarly, major clinical studies on the efficacy of newer antifungals typically do not include cancer patients. Despite the introduction of more potent and less toxic antifungals, mortality from IFIs amongst cancer patients remains high. In recent years, aspergillosis and mucormycosis have also emerged as significant causes of morbidity and mortality amongst ICU patients with haematological cancer.
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ABSTRACT: The Candida Genome Database (CGD, http://www.candidagenome.org/) is a freely available online resource that provides gene, protein and sequence information for multiple Candida species, along with web-based tools for accessing, analyzing and exploring these data. The goal of CGD is to facilitate and accelerate research into Candida pathogenesis and biology. The CGD Web site is organized around Locus pages, which display information collected about individual genes. Locus pages have multiple tabs for accessing different types of information; the default Summary tab provides an overview of the gene name, aliases, phenotype and Gene Ontology curation, whereas other tabs display more in-depth information, including protein product details for coding genes, notes on changes to the sequence or structure of the gene and a comprehensive reference list. Here, in this update to previous NAR Database articles featuring CGD, we describe a new tab that we have added to the Locus page, entitled the Homology Information tab, which displays phylogeny and gene similarity information for each locus.Nucleic Acids Research 10/2013; · 8.81 Impact Factor
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ABSTRACT: C. krusei is intrinsically resistant to fluconazole (FLC). This study aimed to investigate whether tacrolimus (FK506) could enhance the susceptibility of FLC against C. krusei. The tested strains included: five isolates with minimal inhibitory concentration (MIC) of 32 μg mL−1; two with MICs of 256 μg mL−1; one of 512 μg mL−1. MICs of FK506 and FLC alone and in combination were determined by checkerboard assay, with data analyzed by fractional inhibitory concentration index model. The time-kill curves were plotted to investigate the antifungal activity at 0, 6, 12, 24 and 48 h after drug exposure. The results revealed that FK506 reduced the resistance of all isolates obviously and degree of reduction in MICs varied with susceptibilities of strains. Addition of FK506 resulted in a four-fold and sixteen-fold downward shift in MICs of the isolates with MICs of 32 μg mL−1 and of ≥256 μg mL−1, respectively. The synergy was further confirmed by the time-kill assay. When they were in combination against CK4/CK9 with MIC of 32/256 μg mL−1, there was a 2.25/2.03 log10 CFU mL−1 decrease at 24 h compared with FLC alone, respectively. In conclusion, combination of FK506 and FLC may represent a promising approach of overcoming the intrinsic resistance of C. krusei to FLC.This article is protected by copyright. All rights reserved.FEMS Yeast Research 05/2014; · 2.46 Impact Factor
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ABSTRACT: Invasive aspergillosis is a life-threatening lung or systemic infection caused by the opportunistic mold Aspergillus fumigatus. The disease affects mainly immunocompromised hosts, and patients with hematological malignances or who have been submitted to stem cell transplantation are at high risk. Despite the current use of Platelia™ Aspergillus as a diagnostic test, the early diagnosis of invasive aspergillosis remains a major challenge in improving the prognosis of the disease. In this study, we used an immunoproteomic approach to identify proteins that could be putative candidates for the early diagnosis of invasive aspergillosis. Antigenic proteins expressed in the first steps of A. fumigatus germination occurring in a human host were revealed using 2-D Western immunoblots with the serum of patients who had previously been classified as probable and proven for invasive aspergillosis. Forty antigenic proteins were identified using mass spectrometry (MS/MS). A BLAST analysis revealed that two of these proteins showed low homology with proteins of either the human host or etiological agents of other invasive fungal infections. To our knowledge, this is the first report describing specific antigenic proteins of A. fumigatus germlings that are recognized by sera of patients with confirmed invasive aspergillosis who were from two separate hospital units.International Journal of Molecular Sciences 01/2014; 15(8):14505-30. · 2.46 Impact Factor