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      Development and Validation of a Risk Score for Predicting Invasive Candidiasis in Intensive Care Unit Patients by Incorporating Clinical Risk Factors and Lymphocyte Subtyping

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          Abstract

          Objective

          To develop and validate a rapid invasive candidiasis (IC)-predictive risk score in intensive care unit (ICU) patients by incorporating clinical risk factors and parameters of lymphocyte subtyping.

          Methods

          A prospective cohort study of 1054 consecutive patients admitted to ICU was performed. We assessed the clinical characteristics and parameters of lymphocyte subtyping at the onset of clinical signs of infection and their potential influence on IC diagnosis. A risk score for early diagnosis of IC was developed and validated based on a logistic regression model.

          Results

          Sixty-nine patients (6.5%) had IC. Patients in the cohort (N=1054) were randomly divided into a development (n=703) or validation (n=351) cohorts. Multivariate logistic regression identified that CD8+ T-cell count ≤143 cells/mm 3, receipt of high-dose corticosteroids (dose ≥50 mg prednisolone equivalent), receipt of carbapenem/tigecycline, APACHE II score≥15, (1,3)-β-D-glucan (BDG) positivity and emergency gastrointestinal/hepatobiliary (GIT/HPB) surgery were significantly related with IC. IC risk score was calculated using the following formula: CD8+ T-cell count ≤143 cells/mm 3 + receipt of high-dose corticosteroids + receipt of carbapenem/tigecycline + APACHE II score ≥15 + BDG positivity + emergency GIT/HPB surgery ×2. The risk scoring system had good discrimination and calibration with area under the receiver operating characteristic (AUROC) curve of 0.820 and 0.807, and a non-significant Hosmer-Lemeshow test P=0.356 and P=0.531 in the development and validation cohorts, respectively. We categorized patients into three groups according to risk score: low risk (0-2 points), moderate risk (3-4 points) and high risk (5-7 points). IC risk was highly and positively associated with risk score (Pearson contingency coefficient=0.852, P for trend=0.007). Candida score had a moderate predicting efficacy for early IC diagnosis. The AUROC of the risk score was significantly larger than that of Candida score (0.820 versus 0.711, Z=2.013, P=0.044).

          Conclusions

          The predictive scoring system, which used both clinical factors and CD8+ T cell count, served as a clinically useful predictive model for rapid IC diagnosis in this cohort of ICU patients.

          Clinical Trial Registration

          chictr.org.cn, identifier ChiCTR-ROC-17010750.

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          Most cited references25

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          Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.

          Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.
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            Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America.

            It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
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              Septic shock attributed to Candida infection: importance of empiric therapy and source control.

              Delayed treatment of candidemia has previously been shown to be an important determinant of patient outcome. However, septic shock attributed to Candida infection and its determinants of outcome have not been previously evaluated in a large patient population. A retrospective cohort study of hospitalized patients with septic shock and blood cultures positive for Candida species was conducted at Barnes-Jewish Hospital, a 1250-bed urban teaching hospital (January 2002-December 2010). Two hundred twenty-four consecutive patients with septic shock and a positive blood culture for Candida species were identified. Death during hospitalization occurred among 155 (63.5%) patients. The hospital mortality rate for patients having adequate source control and antifungal therapy administered within 24 hours of the onset of shock was 52.8% (n = 142), compared to a mortality rate of 97.6% (n = 82) in patients who did not have these goals attained (P < .001). Multivariate logistic regression analysis demonstrated that delayed antifungal treatment (adjusted odds ratio [AOR], 33.75; 95% confidence interval [CI], 9.65-118.04; P = .005) and failure to achieve timely source control (AOR, 77.40; 95% CI, 21.52-278.38; P = .001) were independently associated with a greater risk of hospital mortality. The risk of death is exceptionally high among patients with septic shock attributed to Candida infection. Efforts aimed at timely source control and antifungal treatment are likely to be associated with improved clinical outcomes.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                27 April 2022
                2022
                : 12
                : 829066
                Affiliations
                [1] 1 Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College , Beijing, China
                [2] 2 Department of Critical Care Medicine, Beijing Jishuitan Hospital , Beijing, China
                Author notes

                Edited by: Alessandro Russo, Magna Græcia University, Italy

                Reviewed by: Nkechi Azie, Scynexis, United States; Fengmei Guo, Southeast University, China; Jianfeng Wu, The First Affiliated Hospital of Sun Yat-sen University, China

                *Correspondence: Hao Wang, newwanghao@ 123456gmail.com ; Na Cui, pumchcn@ 123456163.com

                This article was submitted to Clinical Microbiology, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2022.829066
                9091371
                35573797
                10ee6ec6-6341-4159-8abf-84b483eec19a
                Copyright © 2022 Zhang, Cheng, Li, Chen, Zhao, Wang and Cui

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 December 2021
                : 29 March 2022
                Page count
                Figures: 4, Tables: 4, Equations: 0, References: 25, Pages: 8, Words: 4270
                Categories
                Cellular and Infection Microbiology
                Original Research

                Infectious disease & Microbiology
                invasive candidiasis,risk prediction,critical care,lymphocyte subtyping,cd8+ t cell

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