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
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