Procalcitonin as a diagnostic marker and IL-6 as a prognostic marker for sepsis

Abstract

The diagnosis and prognosis of sepsis after antimicrobial therapy among systemic inflammatory response syndrome (SIRS) patients were evaluated with the biomarkers procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell counts.

Among 177 consecutive SIRS patients, 78 exhibited sepsis, with Escherichia coli (23.1%) being the most common pathogen. PCT showed the best diagnostic performance, with 74.4% and 93.7% sensitivity and 86.7% and 75.2% specificity among sepsis and severe sepsis/septic shock patients, respectively. PCT, IL-6, and CRP levels were significantly increased in nonsurvivors compared to survivors. Serial measurements at 0, 12, 24, 48, 72, and 96 h showed that IL-6 showed better kinetics in the survivor group and was decreased in more than 86% of survivors by the second day.

PCT can support the diagnosis of bacterial infection, especially in septic shock and severe sepsis patients. IL6 exhibited the better kinetics for monitoring the effectiveness of antibiotic treatment.

Introduction

Identification of sepsis in patients with fever and other clinical symptoms and signs is crucial for timely implementation of antimicrobial treatment and predicting prognosis (Giamarellos-Bourboulis et al., 2002). Diagnosis of sepsis is difficult because the signs and symptoms of sepsis overlap with those of viral infections (Hausfater et al., 2007); moreover, sepsis may be obscured by noninfectious causes of systemic inflammatory response syndrome (SIRS) (Tang et al., 2007). In addition, culture-negative bacterial infection hinders the diagnosis of sepsis (Fariñas-Alvarez et al., 2002, Labelle et al., 2010). Microbiologic methods as well as identification of biomarkers and molecular markers have been explored as strategies for detecting sepsis. Among tested biomarkers, procalcitonin (PCT) has been reported to be one of the most accurate (Assicot et al., 1993, Claessens et al., 2010, Meisner et al., 1999, Reinhart and Meisner, 2011). However, the sensitivity and specificity of PCT show marked variation in relation to the severity of infection and cut-off values, with reported sensitivity ranging from 35.0% to 96.5% and specificity ranging from 70.0% to 100% (Brunkhorst et al., 2000, Chan et al., 2004, Gaini et al., 2006, Guven et al., 2001, Hausfater et al., 2002, Suprin et al., 2000). Moreover, some earlier studies have produced conflicting results regarding PCT (Tang et al., 2007). In addition to PCT, C-reactive protein (CRP) has been suggested as a sepsis-related biomarker. The reported sensitivity and specificity ranges for CRP are 63.5% to 76.0% and 74.0% to 84.4%, respectively. White blood cell (WBC) counts, another putative diagnostic indicator of sepsis, shows a sensitivity range of 36.2% to 47.4% and a specificity range of 46.7% to 81.6%.

Clinically, the prognosis of septic patients following treatment is also important. Some studies have shown that PCT might be valuable as a follow-up marker for predicting prognosis in septic or critically ill patients (Clec'h et al., 2004, Jensen et al., 2006, Meisner et al., 1999, Reinhart and Meisner, 2011, Schroder et al., 1999). However, few studies have addressed the potential prognostic value of interleukin-6 (IL-6), CRP, erythrocyte sedimentation rate (ESR), or WBC counts in septic patients.

Therefore, in this study, we evaluated the accuracy of the following inflammatory biomarkers in distinguishing sepsis from SIRS: PCT, IL-6, CRP, ESR, and WBC counts. In addition, these markers were evaluated for their usefulness as follow-up indicators of the success of antimicrobial treatment and predictors of prognosis.