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Observational Study
. 2017 Jul 20;12(7):e0181704.
doi: 10.1371/journal.pone.0181704. eCollection 2017.

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

Lars Ljungström  1 , Anna-Karin Pernestig  2 , Gunnar Jacobsson  1   3 , Rune Andersson  3   4 , Barbara Usener  5 , Diana Tilevik  2
Affiliations
Observational Study

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

Lars Ljungström et al. PLoS One. .

Abstract

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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Conflict of interest statement

Competing Interests: bioMérieux 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.

Figures

Fig 1
Fig 1. Definitions of verified bacterial sepsis, severe bacterial sepsis, and bacterial septic shock according to Sepsis-2 and Sepsis-3, respectively.
SIRS, systemic inflammatory response syndrome; MAP, mean arterial pressure.
Fig 2
Fig 2. Distribution of 1,572 episodes of adult patients with suspected sepsis depending on presence of bacterial infection and whether the criteria for Sepsis-2 and/or Sepsis-3 were fulfilled.
Fig 3
Fig 3. Comparisons of levels of single biomarkers stratified by patient categories.
i. Others (i.e., non-verified bacterial infection, viral infection, and no infection) (n = 698); ii. Verified bacterial infection (n = 874); iii. Verified bacterial sepsis (Sepsis-2) (n = 667); iv. Verified severe bacterial sepsis/septic shock (Sepsis-2) (n = 169); v. Verified bacterial sepsis (Sepsis-3) (n = 560). (A) Procalcitonin (PCT), (B) C-reactive protein (CRP), (C) Lactate, (D) Neutrophil-lymphocyte count ratio (NLCR).
Fig 4
Fig 4. AUC for the biomarkers evaluated in the present study.
Error bars represent 95% CI. The red dotted lines represent a reference line corresponding to AUC = 0.5. The three-biomarker consists of a combination of CRP, lactate, and NLCR, whereas the four-biomarker consists of a combination of PCT, CRP, lactate, and NLCR. (A) AUC for diagnosis of bacteraemia. (B) AUC for diagnosis of verified bacterial infection. (C) AUC for diagnosis of verified bacterial sepsis using Sepsis-2 criteria irrespective severity (i.e., sepsis, severe sepsis, and septic shock). (D) AUC for diagnosis of verified severe bacterial sepsis/septic shock using Sepsis-2 criteria. (E) AUC for diagnosis of verified bacterial sepsis using Sepsis-3 criteria irrespective severity (i.e., sepsis and septic shock). AUC, area under receiver operating caracteristic curve; CI, confidence interval; CRP, C reactive protein; NLCR, neutrophil-lymphocyte ratio; PCT, procalcitonin.
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