Active clinical trials for "Candidiasis, Invasive"

The overarching objective is to develop new evidence-based treatment guidelines for invasive fungal diseases in children. To accomplish that, this protocol will focus on two specific aims: 1) Compare the effectiveness of echinocandin versus amphotericin B or triazole antifungal therapy for pediatric invasive candidiasis and for the subset of patients with invasive candidemia; 2) Characterize the incidence rate of inpatient pediatric invasive candidiasis per hospital admissions.

The purpose of this study is to estimate the relative risk of severe hepatic injury in hospitalized patients with invasive candidiasis and candidemia who received anidulafungin, compared to patients who received caspofungin and/or micafungin.

This is a prospective case-control physiopathological study, which main objective is to determine the genetic host factors predisposing to candidemia. Secondary objectives are to develop new diagnosis tools using the biological collection, to describe and update epidemiology, to analyse the influence of genetic polymorphisms on prognosis.

New rapid diagnostic strategies are warranted in intra-abdominal candidiasis (IAC). A previous retrospective study showed that one measure, the day of the surgery, of peritoneal 1.3-Beta-D-Glucan ≤ 310pg/ml could rule out an IAC. This strategy was independent of the patient underlying conditions and Candida risk factors. This study aimed to confirm these results with a multicenter prospective study

Intra-abdominal candidiasis remains the first origin of invasive candidiasis in critically ill patients with a mortality up to 60%. This high mortality is partly related to delay of anti-fungal treatment administration. According to experts in the field, new diagnostic methods to rapidly detect Candida in intra-abdominal infections is mandatory because the current strategies suffer from a lack of both sensitivity and specificity. The calscreener (SYMCEL®) is a new diagnostic tool to rapidly identify the presence of pathogens in biological samples based on micrometabolic activity detection. This technology also allows to measure the metabolic activity of pathogens. The ICCA project will test the feasibility, the accuracy and the diagnostic performance of the calscreener on an existing biological collection of peritoneal fluid. This collection came from a cohort of critically ill patients with intra-abdominal infection which required abdominal surgery. Intra-abdominal infections consist of bacterial peritonitis and intra-abdominal candidiasis. The presence of pathogens (bacteria and yeast) is already known, the peritoneal fluid being stored after routine analysis (bacteriology / mycology). In addition to the detection / identification of yeast will be investigated in this project, the cal screener will be used to evaluate the metabolic profile of Candida albicans in the peritoneal fluid, alone and with bacteria. This objective aims to evaluate the virulence of Candida in the peritoneal fluid from a metabolic perspective. The results will be compared to phenotypic and molecular evaluation.

The purpose of the study is to 1) define the operating characteristics of fungal biomarker assays in pediatric patients at high-risk for developing invasive candidiasis, 2) determine the change in fungal biomarker assay results in children who develop invasive candidiasis, and 3) create a biobank of blood samples from pediatric patients at high-risk for invasive candidiasis and those with invasive candidiasis for future testing of fungal biomarker assays and development of new fungal biomarker assays. The study will assemble a prospective cohort of pediatric patients at high-risk for developing invasive candidiasis. Blood samples for biomarker testing will be obtained at the time a patient has a clinical indication for blood culture attainment. Additional blood sampling will be performed on the sub-set of patients that are found to have invasive candidiasis. The sensitivity, specificity, PPV, and NPV of biomarker assays will be determined for each biomarker assay. No PHI will be stored in the database and limits on blood draws (3 ml/kg in an 8 week period) will be adhered to.

Epidemiology and clinical outcomes of invasive candidiasis in critically ill patients in Saudi Arabia is not well studied. This observational study objectives include to determine the epidemiology, risk factors and outcomes of invasive Candida infection in critically ill patients in Saudi Arabia.

In critically ill patients Candida spp. are frequently isolated from respiratory tract secretions such as endotracheal aspirates and bronchoalveolar lavages (BAL) and are most often considered as colonizers of the respiratory tract. In contrast, pneumonia due to infection with Candida spp. is rare and is diagnosed by histological demonstration of the yeast in lung tissue with associated inflammation. In spite of this, preemptive antifungal therapy based on isolation of Candida spp. from the respiratory tract is often initiated in critically ill patients. The disadvantages of this approach include increased selective pressure for the development of antimicrobial resistance, potential risks of adverse drug reactions and high treatment costs. On the other hand, immediate administration of appropriate antifungal therapy has been shown to be an important predictor of favorable outcome for patients with invasive fungal infections. Therefore, the development of reliable diagnostic measures for the detection of invasive pulmonary candidiasis is crucial. The overall objective of the proposed research project is to identify diagnostic strategies to differentiate between Candida colonization and Candida infection of the lower respiratory tract in critically ill patients. The proposed projects intends to test the hypothesis that 1.) invasive Candida strains from the lower respiratory tract differ from colonizing Candida strains with regard to production and expression of putative virulence factors and/or that 2.) patients suffering from pulmonary invasive candidiasis differ from patients colonized by Candida spp. with regard to inflammatory markers, other serum markers (fungal antigen) and composition of indigenous pulmonary bacterial flora.

Invasive Candida infections are serious complications in immunocompromised patients including those undergoing treatment for cancer but occur also in patients treated in ICUs. Survival rate of invasive candidiasis is associated with early initiation of antifungal therapy (15% mortality rate for candidemic patients with antifungal therapy on day 0 related to the culture date of the first blood sample positive for yeasts compared to 41% for patients who received antifungal therapy on day 3). Up to date, no laboratory method or clinical decision rule is available for correct anticipation of invasive candidiasis which would avoid delays in appropriate antifungal therapy initiation. In clinical practice culture based methods (e.g. blood cultures) miss up to 50% of invasive candidiasis cases. Preemptive antifungal therapy is therefore often initiated in critically ill patients after Candida has been isolated from various non-sterile patient samples even without any sufficient evidence for invasive candidiasis. The disadvantages of this approach include over- and undertreatment of patients (up to 50% of candidemia cases are missed, and on the other hand 89% patients are treated unnecessarily), increased selective pressure for the development of antifungal resistance, potential risk of adverse drug reactions, and increased costs (expenses for antifungal therapy account for half of the antimicrobial medication budget in tertiary care hospitals). In addition, no survival benefit could be demonstrated by this strategy in ICU patients. The aim of this study is to identify biological markers to anticipate or support the diagnosis of invasive candidiasis in ICU patients, to overcome current deficiencies in detection of invasive candidiasis and consequently to differentiate between Candida spp. colonization and invasive Candida infection. The investigators intend to examine time dependent courses of potential host and pathogen derived biomarkers as well as innate or acquired predispositions for invasive candidiasis; e.g. automated (1→3) ß- D- Glucan tests, DNA in serum blood samples, pathogen recognition receptors and serum markers like interleukin (IL)-1, IL-2, IL-6, IL-10, IL-12, IL-17A, IL-17F, IL-22, IL-23, Tryptophan, Kynurenine, composition of indigenous microbiota of gastrointestinal and lower respiratory tract and skin, and risk factors for invasive candidiasis like underlying diseases and treatments. The study should contribute to improved assessment of ICU patients at risk for invasive candidiasis and to improved diagnosis of invasive candidiasis in ICU patients. In clinical practice the reliable differentiation between infection and colonization will allow more targeted antifungal therapy leading to enhanced antifungal treatment initiation on the one hand (in cases of true invasive candidiasis) and to reduction of unnecessary antifungal treatments and treatment costs on the other hand.

A study of micafungin in ICU versus non-ICU patients showed a significantly lower treatment success in ICU patients compared with non-ICU patients. It is known that in critically ill patients, alterations in function of various organs and body systems can influence the pharmacokinetics and hence the plasma concentration of a drug. The pharmacokinetic parameters of micafungin in critically ill patients are most likely different, but this has not been specifically studied. The pharmacokinetic parameters of micafungin in critically ill patients will be established and plasma concentrations of micafungin will be correlated with disease severity.