(1,3)-ß-D-glucan-based diagnosis of invasive Candida infection versus culture-based diagnosis in patients with sepsis and with an increased risk of invasive Candida infection (CandiSep): study protocol for a randomized controlled trial.

BACKGROUND: The time to diagnosis of invasive Candida infection (ICI) is often too long to initiate timely antifungal therapy in patients with sepsis. Elevated serum (1,3)-ß-D-glucan (BDG) concentrations have a high diagnostic sensitivity for detecting ICI. However, the clinical significance of elevated BDG concentrations is unclear in critically ill patients. The goal of this study is to investigate whether measurement of BDG in patients with sepsis and a high risk for ICI can be used to decrease the time to empiric antifungal therapy and thus, increase survival. METHODS/DESIGN: This prospective multicenter open randomized controlled trial is being conducted in 19 German intensive care units. All adult patients with severe sepsis or septic shock and an increased risk for ICI are eligible for enrolment. Risk factors are total parenteral nutrition, previous abdominal surgery, previous antimicrobial therapy, and renal replacement therapy. Patients with proven ICI or those already treated with systemic antifungal substances are excluded. Patients are allocated to a BDG or standard care group. The standard care group receives targeted antifungal therapy as necessary. In the BDG group, BDG serum samples are taken after randomization and 24 h later. Antifungal therapy is initiated if BDG is ≥80 pg/ml in at least one sample. We plan to enroll 312 patients. The primary outcome is 28-day mortality. Other outcomes include antifungal-free survival within 28 days after enrolment, time to antifungal therapy, and the diagnostic performance of BDG compared to other laboratory tests for early ICI diagnosis. The statistical analysis will be performed according to the intent-to-treat principle. DISCUSSION: Because of the high risk of death, American guidelines recommend empiric antifungal therapy in sepsis patients with a high risk of ICI despite the limited evidence for such a recommendation. In contrast, empiric antifungal therapy is not recommended by European guidelines. BDG may offer a way out of this dilemma since BDG potentially identifies patients in need of early antifungals. However, the evidence for such an approach is inconclusive. This clinical study will generate solid evidence for health-care providers and authors of guidelines for the use of BDG in critically ill patients. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02734550 . Registered 12 April 2016.

Candida-reactive T cells for the diagnosis of invasive Candida infection of the lumbar vertebral spine.

Invasive Candida infection is the fourth most common bloodstream infection. Blood cultures are the current gold standard diagnostic method, however, false negatives remain a clinical challenge. We developed a new technique measuring Candida-reactive T cells as diagnostic read-out for invasive Candida infection. In a pilot study, we followed the treatment course of a patient with an invasive Candida infection of the lumbar vertebral spine. We present the case of a 56-year-old patient with HIV-associated Burkitt lymphoma who developed septic shock during chemotherapy-induced neutropenia. For the first time, we provide flow cytometry-based diagnostics with Candida-reactive T cells for invasive candidiasis with comprehensive MRI imaging. The Candida-reactive T cell assay has potential to complement current diagnostic assays for invasive Candida infection and thus to support targeted treatment.

Evaluación del rendimiento de 1, 3-β -d-glucano como apoyo diagnóstico de infecciones invasoras por Candida spp. en pacientes críticos adultos / The 1,3-β -d-glucan in critical adult patients as diagnostic tool for invasive Candida spp. infection, performance evaluation

Resumen Introducción: La enfermedad fúngica invasora (EFI) se reconoce como causa importante de morbi-mortalidad en pacientes críticos. La mayoría de estas infecciones son provocadas por Candida spp. para cuyo diagnóstico existen importantes limitaciones. Objetivo: Realizar una evaluación inicial de la utilidad de la medición del 1,3-β-D- glucano (BDG) como herramienta diagnóstica de apoyo de las infecciones invasoras por Candida spp. en pacientes críticos. Pacientes y Método: Estudio prospectivo de pacientes mayores de 18 años hospitalizados en unidades de pacientes críticos por más de cinco días, con fiebre sin foco claro y dos o más factores de riesgo para EFI por Candida spp. Se obtuvieron muestras para BDG en dos días consecutivos. Los resultados se confrontaron con el diagnóstico definitivo de candidemia/candidiasis invasora (C/CI) demostrado según cultivos. Resultados: El valor promedio de BDG en los pacientes con diagnóstico de C/CI fue 224,3 ± 213,7 pg/ml y en aquellos sin C/CI 63,8 ± 76,7 pg/ml (p: 0,02). La sensibilidad y especificidad de BDG para diagnóstico de C/CI fue 60 y 92%, respectivamente. El valor predictor positivo fue 60% y el valor predictor negativo de 92%. Conclusión: BDG puede considerarse como un examen de apoyo en el diagnóstico de C/CI en pacientes críticos con factores de riesgo.

Background: Invasive fungal infections are important causes of morbimortality in critical patients. Most of these infections are caused by Candida spp. which diagnosis has important limitations. Aim: Initial evaluation of the utility of 1,3-β-D-glucan (BDG) as a diagnostic tool for invasive candida infections in critical patients. Patients and Methods: Adult patients over 18 years old, hospitalized in intensive care units for more than five days, with fever > 38 °C of unclear origin and two or more risk factors for invasive Candida spp. infection were included. Samples for BDG were obtained on two consecutive days. The results were compared with definitive diagnosis of candidemia/invasive candidiasis (C/IC) confirmed by cultures. Results: Median value of BDG in patients with C/IC was 224.3 ± 213.7 pg/ml and in patients without C/IC was 63.8 ± 76.7 pg/ml (p: 0.02). Sensitivity and specificity for the diagnosis of C/IC were 60 and 92%, respectively. Positive predictive value was 60% and negative predictive value was 92%. Conclusion: BDG could be considered as a complementary diagnostic tool for the diagnosis of C/IC in critical patients with risk factors.

An evaluation of the performance of the Dynamiker® Fungus (1-3)-ß-D-Glucan Assay to assist in the diagnosis of invasive aspergillosis, invasive candidiasis and Pneumocystis pneumonia.

Invasive fungal disease (IFD) can be caused by a range of pathogens. Conventional diagnosis has the capacity to detect most causes of IFD, but poor performance limits impact. The introduction of non-culture diagnostics, including the detection of (1-3)-ß-D-Glucan (BDG), has shown promising performance for the detection of IFD in variety of clinical settings. Recently, the Dynamiker® Fungus (1-3)-ß-D-Glucan assay (D-BDG) was released as an IFD diagnostic test. This article describes an evaluation of the D-BDG assay for the diagnosis of invasive aspergillosis (IA), invasive candidiasis (IC) and Pneumocystis pneumonia (PCP) across several high-risk patient cohorts and provides comparative data with the Associates of Cape Cod Fungitell® and BioRad Platelia™ Aspergillus Ag (GM) assays. There were 163 serum samples from 121 patients tested, from 21 probable IA cases, 28 proven IC cases, six probable PCP cases, one probable IFD case, 14 possible IFD cases and 64 control patients. For proven/probable IFD the mean BDG concentration was 209pg/ml, significantly greater than the control population (73pg/ml; P: <.0001). The sensitivity, specificity, and diagnostic odds ratio for proven/probable IFD was 81.4%, 78.1%, and 15.5, respectively. Significant BDG false positivity (9/13) was associated post abdominal surgery. D-BDG showed fair and good agreement with the Fungitell®, and GM assays, respectively. In conclusion, the D-BDG provides a useful adjunct test to aid the diagnosis of IFD, with technical flexibility that will assist laboratories processing low sample numbers. Further, large scale, prospective evaluation is required to confirm the clinical validity and determine clinical utility.

Infecciones fúngicas en un Servicio de Terapia Intensiva de Adultos de un hospital especializado / Fungal infections in Intensive Care Service of a specialized hospital Adults

RESUMEN Introducción: las infecciones fúngicas son frecuentes en las Unidades de Terapia Intensiva, debida a múltiples factores predisponentes. Objetivos: determinar la prevalencia de infecciones fúngicas y las características clínicas de los pacientes afectados. Metodología: estudio observacional, descriptivo, retrospectivo, realizado en pacientes adultos internados en el Servicio de Terapia Intensiva del Hospital Nacional (Itauguá, Paraguay) en el año 2013. Resultados: fueron incluidos 1034 pacientes, encontrándose 85 con infección por hongos (prevalencia 8,22%). Las especies más frecuentemente aisladas fueron: Cándida spp. (51,76%), C. tropicalis (27,06%) y C. albicans (14,12%). Las comorbilidades más frecuentes fueron hipertensión arterial (91,76%), diabetes mellitus (44,71%) y obesidad (28,24%). Los sitios de aislamientos predominantes fueron el urocultivo (51,76%), hemocultivo (22,35%) y secreción traqueal (21,18%). Hubo 26 óbitos (30,59%). Los factores asociados al óbito fueron los score APACHE y SOFA elevados. Conclusiones: la prevalencia de infecciones fúngicas fue 8,22%, con predominio de Cándida spp. La mortalidad fue 30,59%.

ABSTRACT Introduction: fungal infections are common in intensive care units due to multiple risk factors. Objectives: To determine the prevalence of fungal infections and clinical characteristics of affected patients. Methodology: observational, descriptive and retrospective study, conducted in adult patients admitted to the Intensive Care Service of the National Hospital (Itauguá, Paraguay) in 2013. Results: 1034 patients were included, been 85 with patients affected fungal infection (prevalence 8, 22%). The most frequently isolated species were: Candida spp. (51.76%), C. tropicalis (27.06%) and C. albicans (14.12%). The most common comorbidities were hypertension (91.76%), diabetes mellitus (44.71%) and obesity (28.24%). Predominant sites of isolation were urine culture (51.76%), blood culture (22.35%) and tracheal secretion (21.18%). There were 26 deaths (30.59%). Factors associated with death were the high APACHE score and SOFA. Conclusions: The prevalence of fungal infections were 8.22%, with a predominance of Candida spp. Mortality was 30.59%.

High ferritin levels are associated with hepatosplenic candidiasis in hematopoietic stem cell transplant candidates.

OBJECTIVES: Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Hepatosplenic candidiasis (HSC) is defined as a distinct form of invasive candidiasis, with liver, spleen, and kidney involvement, in patients with hematological disorders. METHODS: The charts of 255 patients (male/female 168/87; median age 35 (range 16-71) years) who were evaluated pre-HSCT at the Gazi University Hospital Stem Cell Transplantation Unit between 2003 and 2008, were retrospectively reviewed. RESULTS: HSC, which was demonstrated in six (2.3%) patients, was found to be more common in allogeneic HSCT recipients than in autologous HSCT recipients and in patients who had received two or more previous chemotherapy courses than in patients who had received fewer than two (p>0.05). Patients with HSC tended to have a worse performance status than patients without HSC according to the World Health Organization (p=0.001) and Karnofsky scale (p=0.007). Pre-transplantation ferritin (p=0.008) and acute phase reactant levels, including erythrocyte sedimentation rate (p=0.025) and C-reactive protein (p=0.007), were significantly higher in patients with HSC than in patients without HSC. CONCLUSIONS: This study shows the predictive role of pre-transplantation ferritin levels in selecting a subset of patients at increased risk for HSC. Pre-transplantation risk assessment and targeted strategies might lower the morbidity and mortality of IFI in HSCT recipients.