Influence of pathogen and focus of infection on procalcitonin values in sepsis patients with bacteremia or candidemia

Daniel O Thomas-Rüddel, Bernhard Poidinger, Matthias Kott, Manfred Weiss, Konrad Reinhart, Frank Bloos, MEDUSA study group, Daniel O Thomas-Rüddel, Bernhard Poidinger, Matthias Kott, Manfred Weiss, Konrad Reinhart, Frank Bloos, MEDUSA study group

Abstract

Background: This study aimed to evaluate the accuracy of procalcitonin (PCT) serum concentrations to diagnose Gram-negative bacteremia and the association of PCT serum concentrations with more specific pathogens and the focus of infection.

Methods: Secondary analysis of the prospectively collected patient-level dataset from a cluster randomized quality improvement trial was performed. The trial included sepsis patients with organ dysfunction treated in the participating intensive care units from 2011 to 2015. Test performance for the prediction of Gram-negative bacteremia was assessed by receiver operating curve analysis. Independent effects of specific pathogen groups and foci of infection on PCT concentrations were assessed by linear logistic regression models.

Results: Blood cultures (BC) and PCT concentrations had been taken in 4858 of 6561 documented patients. PCT was significantly higher in Gram-negative bacteremia compared to Gram-positive bacteremia or candidemia (p < 0.001). The area under the curve was 0.72 (95% confidence interval 0.71-0.74) for the prediction of Gram-negative bacteremia compared to all other blood culture results including negative blood cultures. The optimized cutoff value was 10 ng/ml (sensitivity 69%, specificity 35%). PCT differed significantly between specific groups of pathogens (p < 0.001) with highest concentrations in Escherichia coli, Streptococcus species and other Enterobacteriaceae. PCT was highest in urogenital followed by abdominal infection and lowest in respiratory infection (p < 0.001). In a linear regression model, Streptococci, E. coli and other Enterobacteriaceae detected from BC were associated with three times higher PCT values. Urogenital or abdominal foci of infection were associated with twofold increased PCT values independent of the pathogen.

Conclusions: Serum PCT concentrations are higher in patients with Gram-negative bacteremia than in patients with Gram-positive bacteremia or candidemia. However, the discriminatory power of this difference is too low to guide therapeutic decisions. Variations in PCT serum concentrations are not determined solely by Gram-negative or Gram-positive bacteria but are also affected by distinct groups of pathogens and different foci of infection.

Trial registration: ClinicalTrials.gov, NCT01187134 . Registered on 23 August 2010.

Keywords: Bacteremia; Focal infection; Gram-negative bacteria; Gram-positive bacteria; Procalcitonin; Sepsis.

Conflict of interest statement

Ethics approval and consent to participate

The original trial whose dataset was analyzed was approved by the local ethics committees at each participating institution and by the responsible state data protection boards. The need for informed consent was waived by all committees and data protection boards. The main vote was by the ethics committee of the University Hospital Jena (2910-08/10). A list of all involved ethical bodies is supplied as Additional file 1. No ethics approval was necessary for this secondary analysis.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Initial PCT concentrations (ng/ml, median and IQR) associated with Gram stain (a) or type of pathogen (b) detected in blood culture drawn at sepsis onset, or associated with focus of infection (c). Significantly different (p < 0.001) in all three comparisons. n denotes number of cases represented by each bar and superscript letters denote homogeneous subsets
Fig. 2
Fig. 2
Median and IQR of PCT concentrations associated with focus of infection in combination with most frequent blood culture results. Associations of focus and pathogens independent from each other (see Tables 5 and 6)

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