Neutrophil CD64 expression as a diagnostic marker for sepsis in adult patients: a meta-analysis

Wang et al. Critical Care (2015) 19:245 DOI 10.1186/s13054-015-0972-z RESEARCH Open Access Neutrophil CD64 expression as a diagnostic marker for sepsis in adult patients: a meta-analysis Xiao Wang1, Zhong-Yun Li2, Ling Zeng1, An-Qiang Zhang3, Wei Pan1, Wei Gu1* and Jian-Xin Jiang1* Abstract Introduction: Neutrophil CD64 (nCD64) expression appears to be a promising marker of bacterial infections. The aim of this meta-analysis was to assess the accuracy of nCD64 expression for the diagnosis of sepsis in critically ill adult patients. Methods: We systematically searched PubMed, Embase, ISI Web of Knowledge, and the Cochrane Library for literature published between database inception and 19 May 2014, as well as reference lists of identified primary studies. Studies were included if they included assessment of the accuracy of nCD64 expression for sepsis diagnosis in adult patients and provided sufficient information to construct a 2×2 contingency table. Results: A total of 8 studies comprising 1986 patients fulfilled the inclusion criteria for the final analysis. The pooled sensitivity and specificity were 0.76 (95 % confidence interval [CI], 0.73–0.78) and 0.85 (95 % CI, 0.82–0.87), respectively. The positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio were 8.15 (95 % CI, 3.82–17.36), 0.16 (95 % CI, 0.09–0.30), and 60.41 (95 % CI, 15.87–229.90), respectively. The area under the summary receiver operating characteristic curve of nCD64 expression with Q* value were 0.95 (Q* =0.89). Conclusions: On the basis of our meta-analysis, nCD64 expression is a helpful marker for early diagnosis of sepsis in critically ill patients. The results of the test should not be used alone to diagnose sepsis, but instead should be interpreted in combination with medical history, physical examination, and other test results. Introduction Sepsis is the most common cause of mortality in critically ill patients worldwide [1]. Delays in diagnosis and treatment often result in rapid progression to circulatory collapse, multiple organ failure, and eventually death [2]. Therefore, early diagnosis sepsis and timely treatment can improve patients’ outcome and reduce costs [3, 4]. The diagnosis of sepsis is sometimes challenging, because the diagnosis is based on systemic inflammatory response syndrome (SIRS) in the presence of a known infection. SIRS is very common in many conditions, such as surgery, trauma, and pancreatitis [5, 6]. Microbiological culture is a gold standard for distinguishing sepsis from non-infectious conditions. However, incubation of bacteria * Correspondence: ; 1 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Changjiang Road 10 Yuzhong District, Chongqing, China Full list of author information is available at the end of the article may take a long time, and during this period, the condition of patients may rapidly deteriorate. Additionally, blood culture always has poor sensitivity [7]. Thus, there is an urgent need of a biomarker that can identify sepsis in an early stage so that timely and appropriate use of antibiotics can be initiated [8]. CD64, one of the high-affinity immunoglobulin Fcγ receptors, is constitutively expressed on monocytes and eosinophils. Recently, an increasing number of studies have been performed to investigate the role of neutrophil CD64 (nCD64) expression in the diagnosis of bacterial infection and sepsis [9–22]. Davis et al. indicated that nCD64 expression could improve the accuracy of diagnosing infection or sepsis [9]. Cardelli et al. reported that nCD64 expression had higher sensitivity and specificity than procalcitonin (PCT) in detecting sepsis [10]. However, these studies had limited numbers of patients and conflicting results [11–13]; thus, no firm conclusions could be drawn. © 2016 Wang et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Wang et al. Critical Care (2015) 19:245 The authors of some meta-analyses have investigated the accuracy of nCD64 expression for the diagnosis of bacterial infection [23–25]. However, these studies included adults, children, and neonates, and patients with rheumatoid arthritis, local infections, and sepsis were mixed. None of these studies specially investigated the ability of nCD64 to diagnose sepsis in critically ill patients. Additionally, many more related studies have been published during the last 2 years. We aimed to conduct a meta-analysis to investigate the role of nCD64 expression for sepsis diagnosis in critically ill adult patients. Methods A protocol was designed before this study was undertaken, as recommended by the Quality of Reporting of Meta-analyses statement [26]. All analyses are based on previously published studies; thus, neither ethical approval nor patient consent was required. Search strategy and selection criteria We systematically searched PubMed, Embase, ISI Web of Knowledge, and the Cochrane Library to identify all studies that included assessment of the accuracy of nCD64 expression for the diagnosis of sepsis. Our search terms were “(CD64 OR “Fc gamma receptor”) AND (sepsis OR “septic shock” OR septicemia).” We searched the databases for literature published between database inception and 19 May 2014. Additionally, the reference lists of each primary study identified, as well as previous review articles, were hand-searched to identify other potentially eligible studies. Eligibility of a study for the meta-analysis was based on the following selection criteria: assessed the diagnostic accuracy of nCD64 expression for sepsis; had a welldefined reference standard for sepsis, which included the use of accepted definitions by the American College of Chest Physicians/Society of Critical Care Medicine [27]; and provided sufficient information to construct a 2×2 contingency table. We included only publications written in English. Studies conducted on special groups of neonates and those that included patients who did not have SIRS or were not critically ill were excluded. Two investigators (XW and ZYL) reviewed all the studies independently. Disagreements were resolved through discussion with a third investigator (AQZ). Data extraction Two investigators (XW and ZYL) reviewed all eligible studies and carefully extracted data. The data extracted from each study included the following details: first author, publication year, country of origin, clinical setting, patient demographics, sample size, analytical method, cutoff value, sensitivity, and specificit (...truncated)