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Impact of the Beta-Glucan Test on Management of Intensive Care Unit Patients at Risk for Invasive Candidiasis.

ABSTRACT: The 1,3-beta-d-glucan (BDG) test is used for the diagnosis of invasive candidiasis (IC) in intensive care units (ICUs). However, its utility for patient management is unclear. This study assessed the impact of BDG test results on therapeutic decisions. This was a single-center observational study conducted in an ICU over two 6-month periods. All BDG test requests for the diagnosis of IC were analyzed. Before the second period, the ICU physicians received a pocket card instruction (algorithm) for targeted BDG testing in high-risk patients. The performance of the BDG test for IC diagnosis was assessed, as well as its impact on antifungal (AF) prescription. Overall, 72 patients had ?1 BDG test, and 14 (19%) patients had an IC diagnosis. The BDG test results influenced therapeutic decisions in 41 (57%) cases. The impact of the BDG test was positive in 30 (73%) of them, as follows: AF abstention/interruption following a negative BDG result (n?=?27), and AF initiation/continuation triggered by a positive BDG test result and subsequently confirmed IC (n?=?3). In 10 (24%) cases, a positive BDG test result resulted in AF initiation/continuation with no further evidence of IC. A negative BDG result and AF abstention with subsequent IC diagnosis were observed in one case. The positive predictive value (PPV) of BDG was improved if testing was restricted to the algorithm's indications (80% versus 36%, respectively). However, adherence to the algorithm was low (26%), and no benefit of the intervention was observed. The BDG result had an impact on therapeutic decisions in more than half of the cases, which consisted mainly of safe AF interruption/abstention. Targeted BDG testing in high-risk patients improves PPV but is difficult to achieve in ICU.

SUBMITTER: Kritikos A

PROVIDER: S-EPMC7269378 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Impact of the Beta-Glucan Test on Management of Intensive Care Unit Patients at Risk for Invasive Candidiasis.

Kritikos Antonios A Poissy Julien J Croxatto Antony A Bochud Pierre-Yves PY Pagani Jean-Luc JL Lamoth Frederic F

Journal of clinical microbiology 20200526 6

The 1,3-beta-d-glucan (BDG) test is used for the diagnosis of invasive candidiasis (IC) in intensive care units (ICUs). However, its utility for patient management is unclear. This study assessed the impact of BDG test results on therapeutic decisions. This was a single-center observational study conducted in an ICU over two 6-month periods. All BDG test requests for the diagnosis of IC were analyzed. Before the second period, the ICU physicians received a pocket card instruction (algorithm) for ...[more]

PMID: 32238435

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Project description:BackgroundTo investigate the impact of initial antifungal therapeutic strategies on the prognosis of invasive Candida infections (ICIs) in intensive care units (ICUs) in China.MethodsA total of 306 patients with proven ICIs in the China-SCAN study were analyzed retrospectively. Empiric, pre-emptive, and targeted therapy were adopted based on starting criteria including clinical, microbiological, and other conventional prediction rules. The primary outcome was hospital mortality and the secondary endpoints were duration days in ICU and duration days in hospital. The global responses (clinical and microbiological) at the end of the empirical therapy were also assessed.ResultsA total of 268/306 (87.6%) ICI patients received antifungal therapy, including 142/268 (53.0%) initial empirical therapy, 53/268 (19.8%) initial pre-emptive therapy, and 73/268 (27.2%) initial targeted therapy. Compared with the initial empirical antifungal therapy and targeted antifungal therapy, patients with initial pre-emptive antifungal therapy had significantly less clinical remission [11/53 (21.2%) vs. 61/142 (43.3%) vs. 22/73 (30.1%), P = 0.009], higher ICU [26/53 (57.8%) vs. 42/142 (32.2%) vs. 27/73 (43.5%), P = 0.008] and hospital mortality [27/53 (60.0%) vs. 43/142 (32.8%) vs. 29/73 (46.8%), P = 0.004] and more microbiological persistence [9/53 (17.0%) vs. 6/142 (4.2%) vs. 9/73 (12.3%), P = 0.011]. Kaplan-Meier survival analysis revealed that ICI patients with initial pre-emptive antifungal therapy and targeted antifungal therapy were associated with reduced hospital duration compared with patients with initial empirical antifungal therapy after confirmation of fungal infection (log-rank test: P = 0.021). Multivariate regression analysis provided evidence that initial empirical antifungal therapy was an independent predictor for DECREASING the hospital mortality in ICI patients on ICU admission and at ICI diagnosis (odds ratio 0.327, 95% confidence interval 0.160-0.667, P = 0.002; odds ratio 0.351, 95% confidence interval 0.168-0.735, P = 0.006).ConclusionsThe initial therapeutic strategy for invasive candidiasis was independently associated with hospital mortality. Prompt empirical antifungal therapy could be critical to decrease early hospital mortality.Trial registrationClinicaltrials.gov NCT01253954 (retrospectively registration date: December 3, 2010).

Project description:Background(1,3)-β-D-Glucan has been widely used in clinical practice for the diagnosis of invasive Candida infections. However, such serum biomarker showed potential to guide antimicrobial therapy in order to reduce the duration of empirical antifungal treatment in critically ill septic patients with suspected invasive candidiasis.MethodsThis was a single-centre, randomized, open-label clinical trial in which critically ill patients were enrolled during the admission to the intensive care unit (ICU). All septic patients who presented invasive Candida infection risk factors and for whom an empirical antifungal therapy was commenced were randomly assigned (1:1) in those stopping antifungal therapy if (1,3)-β-D-glucan was negative ((1,3)-β-D-glucan group) or those continuing the antifungal therapy based on clinical rules (control group). Serum 1,3-β-D-glucan was measured at the enrolment and every 48/72 h over 14 days afterwards. The primary endpoint was the duration of antifungal treatment in the first 30 days after enrolment.ResultsWe randomized 108 patients into the (1,3)-β-D-glucan (n = 53) and control (n = 55) groups. Median [IQR] duration of antifungal treatment was 2 days [1-3] in the (1,3)-β-D-glucan group vs. 10 days [6-13] in the control group (between-group absolute difference in means, 6.29 days [95% CI 3.94-8.65], p < 0.001). Thirty-day mortality was similar (28.3% [(1,3)-β-D-glucan group] vs. 27.3% [control group], p = 0.92) as well as the overall rate of documented candidiasis (11.3% [(1,3)-β-D-glucan group] vs. 12.7% [control group], p = 0.94), the length of mechanical ventilation (p = 0.97) and ICU stay (p = 0.23).ConclusionsIn critically ill septic patients admitted to the ICU at risk of invasive candidiasis, a (1,3)-β-D-glucan-guided strategy could reduce the duration of empirical antifungal therapy. However, the safety of this algorithm needs to be confirmed in future, multicentre clinical trial with a larger population.Trial registrationClinicalTrials.gov, NCT03117439 , retrospectively registered on 18 April 2017.

Project description:Critically ill intensive care unit (ICU) patients commonly develop severe muscle wasting and impaired muscle function, leading to delayed recovery, with subsequent increased morbidity and financial costs, and decrease quality of life of survivors. Acute Quadriplegic Myopathy (AQM) is one of the most common neuromuscular disorders associated with ICU-acquired muscle weakness. Although there are no available treatments for the ICU-acquired muscle weakness, it has been demonstrated that early mobilization can improve its prognosis and functional outcomes. This study aims at improving our understanding of the effects of passive mechanical loading on skeletal muscle structure and function by using a unique experimental rat ICU model allowing analyses of the temporal sequence of changes in mechanically ventilated and pharmacologically paralyzed animals at durations varying from 6 h to 14 days. Results show that passive mechanical loading alleviated the muscle wasting and the loss of force-generation associated with the ICU intervention, resulting in a doubling of the functional capacity of the loaded vs. unloaded muscles after a 2-week ICU intervention. We demonstrated that the improved maintenance of muscle structure and function is likely a consequence of a reduced oxidative stress, and a reduced loss of the molecular motor protein myosin. A complex temporal gene expression pattern, delineated by microarray analysis, was observed with loading-induced changes in transcript levels of sarcomeric proteins, muscle developmental processes, stress response, ECM/cell adhesion proteins and metabolism. Thus, the results from this study show that passive mechanical loading alleviates the severe negative consequences on muscle structure and function associated with mechanical silencing in ICU patients, strongly supporting early and intense physical therapy in immobilized ICU patients. This study aims to unravel the effects of passive mechanical loading on skeletal muscle structure and function in an experimental rat ICU model at duration varying between 6h and 14 days. A total of 23 experimental female Sprague-Dawley rats were included in this study. The experimental rats were anaesthetized, treated with the neuromuscular blocking agent (NMBA) M-NM-1-cobrotoxin, mechanically ventilated and monitored for durations varying from 6h to 4 days (n=13), from 5 to 8 days (n=4), and from 9 to 14 days (n=6). The left leg of the animal was activated for 6 hours at the shortest duration and 12 hours per day at durations 12 hours and longer throughout the experiment, using a mechanical lever arm that produced a continuous passive maximal ankle joint flexions-extensions at a speed of 13.3 cycles per minute. Muscle biopsies were obtained from gastrocnemius muscle (proximal part) immediately after euthanasia, were quickly frozen in liquid propane cooled by liquid nitrogen, and stored at -80M-BM-0C. RNA was extracted.

Project description:ObjectiveTo 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.MethodsA 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.ResultsSixty-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/mm3, 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/mm3 + 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).ConclusionsThe 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 registrationchictr.org.cn, identifier ChiCTR-ROC-17010750.

Dataset Information

Impact of the Beta-Glucan Test on Management of Intensive Care Unit Patients at Risk for Invasive Candidiasis.

Publications

Impact of the Beta-Glucan Test on Management of Intensive Care Unit Patients at Risk for Invasive Candidiasis.

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