Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis

PLOS ONE, Dec 2019

Background Early recognition is a key factor to achieve improved outcomes for septic patients. Combinations of biomarkers, as opposed to single ones, may improve timely diagnosis and survival. We investigated the performance characteristics of sepsis biomarkers, alone and in combination, for diagnosis of verified bacterial sepsis using Sepsis-2 and Sepsis-3 criteria, respectively. Methods Procalcitonin (PCT), neutrophil-lymphocyte count ratio (NLCR), C-reactive protein (CRP), and lactate were determined in a total of 1,572 episodes of adult patients admitted to the emergency department on suspicion of sepsis. All sampling were performed prior to antibiotic administration. Discriminant analysis was used to construct two composite biomarkers consisting of linear combinations of the investigated biomarkers, one including three selected biomarkers (i.e., NLCR, CRP, and lactate), and another including all four (i.e., PCT, NLCR, CRP, and lactate). The diagnostic performances of the composite biomarkers as well as the individual biomarkers were compared using the area under the receiver operating characteristic curve (AUC). Results For diagnosis of bacterial sepsis based on Sepsis-3 criteria, the AUC for PCT (0.68; 95% CI 0.65–0.71) was comparable to the AUCs for the both composite biomarkers. Using the Sepsis-2 criteria for bacterial sepsis diagnosis, the AUC for the NLCR (0.68; 95% CI 0.65–0.71) but not for the other single biomarkers, was equal to the AUCs for the both composite biomarkers. For diagnosis of severe bacterial sepsis or septic shock based on the Sepsis-2 criteria, the AUCs for both composite biomarkers were significantly greater than those of the single biomarkers (0.85; 95% CI 0.82–0.88 for the composite three-biomarker, and 0.86; 95% CI 0.83–0.89 for the composite four-biomarker). Conclusions Combinations of biomarkers can improve the diagnosis of verified bacterial sepsis in the most critically ill patients, but in less severe septic conditions either the NLCR or PCT alone exhibit equivalent performance.

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Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis

July Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis Lars LjungstroÈ m 0 1 Anna-Karin Pernestig 1 Gunnar Jacobsson 0 1 Rune Andersson 1 Barbara Usener 1 Diana Tilevik 1 0 Department of Infectious Diseases, Skaraborg Hospital, SkoÈvde, Sweden, 2 Systems Biology Research Centre, School of Bioscience, University of Sk oÈvde, Sk oÈvde, Sweden, 3 CARe±Center for Antibiotic Resistance Research, Gothenburg University , Gothenburg , Sweden , 4 Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University and Sahlgrenska University Hospital , Gothenburg , Sweden , 5 Department of Clinical Chemistry , Unilabs AB, SkoÈvde , Sweden 1 Editor: Luciano Cesar Pontes Azevedo, Hospital Sirio-Libanes , BRAZIL Background Early recognition is a key factor to achieve improved outcomes for septic patients. Combina tions of biomarkers, as opposed to single ones, may improve timely diagnosis and survival. We investigated the performance characteristics of sepsis biomarkers, alone and in combination, for diagnosis of verified bacterial sepsis using Sepsis-2 and Sepsis-3 criteria, respectively. Methods Procalcitonin (PCT), neutrophil-lymphocyte count ratio (NLCR), C-reactive protein (CRP), and lactate were determined in a total of 1,572 episodes of adult patients admitted to the emergency department on suspicion of sepsis. All sampling were performed prior to antibiotic administration. Discriminant analysis was used to construct two composite biomarkers consisting of linear combinations of the investigated biomarkers, one including three selected biomarkers (i.e., NLCR, CRP, and lactate), and another including all four (i.e., PCT, NLCR, CRP, and lactate). The diagnostic performances of the composite biomarkers as well as the individual biomarkers were compared using the area under the receiver operating characteristic curve (AUC). Results For diagnosis of bacterial sepsis based on Sepsis-3 criteria, the AUC for PCT (0.68; 95% CI 0.65±0.71) was comparable to the AUCs for the both composite biomarkers. Using the Sepsis-2 criteria for bacterial sepsis diagnosis, the AUC for the NLCR (0.68; 95% CI 0.65±0.71) but not for the other single biomarkers, was equal to the AUCs for the both composite biomarkers. For diagnosis of severe bacterial sepsis or septic shock based on the Sepsis-2 beredningsgrupp/), and internal Unilabs R&D Fund (www.unilabs.se). The funding bodies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: bioMeÂrieux Sweden AB (Askim, Sweden) provided instrument for PCT analysis and discount on the used PCT kits. This does not alter our adherence to PLOS ONE policies on sharing data and materials. criteria, the AUCs for both composite biomarkers were significantly greater than those of the single biomarkers (0.85; 95% CI 0.82±0.88 for the composite three-biomarker, and 0.86; 95% CI 0.83±0.89 for the composite four-biomarker). Conclusions Combinations of biomarkers can improve the diagnosis of verified bacterial sepsis in the most critically ill patients, but in less severe septic conditions either the NLCR or PCT alone exhibit equivalent performance. Introduction Sepsis is a life-threatening condition that arises when the host responds to an infection and damages its organs [ 1 ]. It is often difficult to distinguish between bacterial and non-bacterial aetiologies early in suspected sepsis. Clinical signs of sepsis such as tachycardia, leucocytosis, tachypnea, and pyrexia, often overlap with other non-infectious conditions in critically ill patients. Concurrently, it has been shown that prompt diagnosis and early administration of appropriate antibiotic therapy considerably improve the outcomes of septic patients [2±4]. The difficulty in distinguishing between bacterial and non-bacterial aetiologies is also a major cause of the misuse of antibiotics [ 5 ]. Inappropriate or prolonged use of antibiotics may lead to the emergence of antibiotic resistant bacteria [6±8] and to various adverse events [9±11], whereas antibiotic underuse due to delayed or missed diagnosis may result in worsened condition and medical complications [12±16]. There is an unmet need for diagnostic tools differentiating between bacterial and non-bacterial causes of sepsis. Although various biomarkers have been proposed, no single clinical or biological indicator of sepsis has gained general acceptance [17, 18]. The most widely studied biomarkers in patients with suspected bacterial sepsis are C-reactive protein (CRP) and procalcitonin (PCT). Both CRP and PCT are today routinely employed in clinical practice but have limited abilities to distinguish bacterial sepsis from other inflammatory conditions [19]. Even if PCT has an established role as biomarker in septic patients, the diagnostic accuracy of ro (...truncated)


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Lars Ljungström, Anna-Karin Pernestig, Gunnar Jacobsson, Rune Andersson, Barbara Usener, Diana Tilevik. Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis, PLOS ONE, 2017, Volume 12, Issue 7, DOI: 10.1371/journal.pone.0181704