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      CD64 and Group II Secretory Phospholipase A2 (sPLA2-IIA) as Biomarkers for Distinguishing Adult Sepsis and Bacterial Infections in the Emergency Department

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          Abstract

          Introduction

          Early diagnosis of sepsis and bacterial infection is imperative as treatment relies on early antibiotic administration. There is a need to develop new biomarkers to detect patients with sepsis and bacterial infection as early as possible, thereby enabling prompt antibiotic treatment and improving the survival rate.

          Methods

          Fifty-one adult patients with suspected bacterial sepsis on admission to the Emergency Department (ED) of a teaching hospital were included into the study. All relevant cultures and serology tests were performed. Serum levels for Group II Secretory Phospholipase A2 (sPLA2-IIA) and CD64 were subsequently analyzed.

          Results and Discussion

          Sepsis was confirmed in 42 patients from a total of 51 recruited subjects. Twenty-one patients had culture-confirmed bacterial infections. Both biomarkers were shown to be good in distinguishing sepsis from non-sepsis groups. CD64 and sPLA2-IIA also demonstrated a strong correlation with early sepsis diagnosis in adults. The area under the curve (AUC) of both Receiver Operating Characteristic curves showed that sPLA2-IIA was better than CD64 (AUC = 0.93, 95% confidence interval (CI) = 0.83–0.97 and AUC = 0.88, 95% CI = 0.82–0.99, respectively). The optimum cutoff value was 2.13μg/l for sPLA2-IIA (sensitivity = 91%, specificity = 78%) and 45 antigen bound cell (abc) for CD64 (sensitivity = 81%, specificity = 89%). In diagnosing bacterial infections, sPLA2-IIA showed superiority over CD64 (AUC = 0.97, 95% CI = 0.85–0.96, and AUC = 0.95, 95% CI = 0.93–1.00, respectively). The optimum cutoff value for bacterial infection was 5.63μg/l for sPLA2-IIA (sensitivity = 94%, specificity = 94%) and 46abc for CD64 (sensitivity = 94%, specificity = 83%).

          Conclusions

          sPLA2-IIA showed superior performance in sepsis and bacterial infection diagnosis compared to CD64. sPLA2-IIA appears to be an excellent biomarker for sepsis screening and for diagnosing bacterial infections, whereas CD64 could be used for screening bacterial infections. Both biomarkers either alone or in combination with other markers may assist in decision making for early antimicrobial administration. We recommend incorporating sPLA2-IIA and CD64 into the diagnostic algorithm of sepsis in ED.

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          Most cited references53

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          Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock.

          Serum lactate is a potentially useful biomarker to risk-stratify patients with severe sepsis; however, it is plausible that elevated serum lactate is simply a manifestation of clinically apparent organ dysfunction and/or shock (i.e., refractory hypotension). To test whether the association between initial serum lactate level and mortality in patients presenting to the emergency department (ED) with severe sepsis is independent of organ dysfunction and shock. Single-center cohort study. The primary outcome was 28-day mortality and the risk factor variable was initial venous lactate (mmol/L), categorized as low ( or = 4). Potential covariates included age, sex, race, acute and chronic organ dysfunction, severity of illness, and initiation of early goal-directed therapy. Multivariable logistic regression analyses were stratified on the presence or absence of shock. The ED of an academic tertiary care center from 2005 to 2007. Eight hundred thirty adults admitted with severe sepsis in the ED. None. Mortality at 28 days was 22.9% and median serum lactate was 2.9 mmol/L. Intermediate (odds ratio [OR] = 2.05, p = 0.024) and high serum lactate levels (OR = 4.87, p < 0.001) were associated with mortality in the nonshock subgroup. In the shock subgroup, intermediate (OR = 3.27, p = 0.022) and high serum lactate levels (OR = 4.87, p = 0.001) were also associated with mortality. After adjusting for potential confounders, intermediate and high serum lactate levels remained significantly associated with mortality within shock and nonshock strata. Initial serum lactate was associated with mortality independent of clinically apparent organ dysfunction and shock in patients admitted to the ED with severe sepsis. Both intermediate and high serum lactate levels were independently associated with mortality.
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            Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis.

            Procalcitonin is widely reported as a useful biochemical marker to differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome. In this systematic review, we estimated the diagnostic accuracy of procalcitonin in sepsis diagnosis in critically ill patients. 18 studies were included in the review. Overall, the diagnostic performance of procalcitonin was low, with mean values of both sensitivity and specificity being 71% (95% CI 67-76) and an area under the summary receiver operator characteristic curve of 0.78 (95% CI 0.73-0.83). Studies were grouped into phase 2 studies (n=14) and phase 3 studies (n=4) by use of Sackett and Haynes' classification. Phase 2 studies had a low pooled diagnostic odds ratio of 7.79 (95% CI 5.86-10.35). Phase 3 studies showed significant heterogeneity because of variability in sample size (meta-regression coefficient -0.592, p=0.017), with diagnostic performance upwardly biased in smaller studies, but moving towards a null effect in larger studies. Procalcitonin cannot reliably differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome in critically ill adult patients. The findings from this study do not lend support to the widespread use of the procalcitonin test in critical care settings.
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              Comparison of procalcitonin and C-reactive protein as markers of sepsis.

              To compare the clinical informative value of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations in the detection of infection and sepsis and in the assessment of severity of sepsis. Prospective study. Medicosurgical intensive care unit. Seventy consecutive adult patients who were admitted to the intensive care unit for an expected stay >24 hrs. None. PCT and CRP plasma concentrations were measured daily during the intensive care unit stay. Each patient was examined daily for signs and symptoms of infection and was classified daily in one of the following four categories according to the American College of Chest Physicians/Society of Critical Care Medicine criteria: negative, systemic inflammatory response syndrome, localized infection, and sepsis group (sepsis, severe sepsis, or septic shock). The severity of sepsis-related organ failure was assessed by the sepsis-related organ failure assessment score. A total of 800 patient days were classified into the four categories. The median plasma PCT concentrations in noninfected (systemic inflammatory response syndrome) and localized-infection patient days were 0.4 and 1.4 ng/mL (p <.0001), respectively; the median CRP plasma concentrations were 79.9 and 85.3 mg/L (p =.08), respectively. The area under the receiver operating characteristic curve was 0.756 for PCT (95% confidence interval [CI], 0.675-0.836), compared with 0.580 for CRP (95% CI, 0.488-0.672) (p <.01). The median plasma PCT concentrations in nonseptic (systemic inflammatory response syndrome) and septic (sepsis, severe sepsis, or septic shock) patient days were 0.4 and 3.65 ng/mL (p <.0001), respectively, whereas those for CRP were 79.9 and 115.6 mg/L (p <.0001), respectively. The area under the receiver operating characteristic curve was 0.925 for PCT (95% CI, 0.899-0.952), compared with 0.677 for CRP (95% CI, 0.622-0.733) (p <.0001). The linear correlation between PCT plasma concentrations and the four categories was much stronger than in the case of CRP (Spearman's rho, 0.73 vs. 0.41; p <.05). A rise in sepsis-related organ failure assessment score was related to a higher median value of PCT but not CRP. PCT is a better marker of sepsis than CRP. The course of PCT shows a closer correlation than that of CRP with the severity of infection and organ dysfunction.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 March 2016
                2016
                : 11
                : 3
                : e0152065
                Affiliations
                [1 ]Department of Emergency Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
                [2 ]Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
                [3 ]Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
                Rutgers University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: TLT. Performed the experiments: TLT NSA DNN AI KTA. Analyzed the data: TLT NSA DNN AI KTA. Contributed reagents/materials/analysis tools: TLT NSA DNN AI KTA IZZ WZWN. Wrote the paper: TLT NSA DNN AI KTA IZZ WZWN.

                [¤]

                Current address: Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia

                Article
                PONE-D-15-52584
                10.1371/journal.pone.0152065
                4803226
                27003588
                34f25638-9ec1-425c-a5bb-5d663fe03723
                © 2016 Tan et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 4 December 2015
                : 8 March 2016
                Page count
                Figures: 7, Tables: 3, Pages: 14
                Funding
                This study was supported by the ‘Geran Galakan Penyelidik Muda’ (GGPM-2013-103) and Economic Transformation Programme Research Fund Scheme (ETP-2013-050) from Universiti Kebangsaan Malaysia.
                Categories
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                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Sepsis
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                Pathology and Laboratory Medicine
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                Sepsis
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                Biochemistry
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