How to use biomarkers of infection or sepsis at the bedside: guide to clinicians

Abstract

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In this context, biomarkers could be considered as indicators of either infection or dysregulated host response or response to treatment and/or aid clinicians to prognosticate patient risk. More than 250 biomarkers have been identified and evaluated over the last few decades, but no biomarker accurately differentiates between sepsis and sepsis-like syndrome. Published data support the use of biomarkers for pathogen identification, clinical diagnosis, and optimization of antibiotic treatment. In this narrative review, we highlight how clinicians could improve the use of pathogen-specific and of the most used host-response biomarkers, procalcitonin and C-reactive protein, to improve the clinical care of patients with sepsis. Biomarker kinetics are more useful than single values in predicting sepsis, when making the diagnosis and assessing the response to antibiotic therapy. Finally, integrated biomarker-guided algorithms may hold promise to improve both the diagnosis and prognosis of sepsis. Herein, we provide current data on the clinical utility of pathogen-specific and host-response biomarkers, offer guidance on how to optimize their use, and propose the needs for future research.

Keywords: Antibiotic stewardship; Biomarkers; Diagnosis; Intensive care unit; Sepsis.

Fig. 1

The three vectors of the sepsis approach: systemic manifestations, organ dysfunction and microbiological documentation (see text). Biomarkers could provide additional information in the vector systemic manifestations (host-response biomarkers e.g., C-reactive protein–CRP, and procalcitonin–PCT), organ dysfunction (e.g., kidney injury biomarkers) and microbiological documentation (pathogen-specific biomarkers—see Table 1). Biomarkers can be classified as prognostic, predictive and theranostic. Prediction refers also to the ability of a biomarker to predict the occurrence of sepsis before its clinical suspicion (presymptomatic) as well as identify the response to therapy. For this purpose, biomarkers kinetics are more informative than a single value. A useful biomarker for the assessment of response to therapy should decline or return to baseline levels with successful therapy or remain elevated or increase if sepsis is treatment-refractory. To evaluate the clinical course, the biomarker should exhibit a large amplitude of variation, and neither ‘exhaustion’ nor ‘fatigue’ behavior with prolonged sepsis episodes

Fig. 2

User's guide for biomarker-guided antibiotic therapy. Starting antibiotics in critically ill patients with suspicion of sepsis should be done irrespective of any biomarker level. But this should be reassessed daily. Use the clinical course, the organ dysfunction course (with SOFA score), the kinetics of biomarkers and the duration of antibiotic therapy to ascertain the optimal duration of therapy. PCT, procalcitonin; CRP, C-reactive protein; SOFA, sequential organ failure assessment, NOTE–CRP and PCT thresholds should be used only as indicative and orientation; These recommendations do not apply to immune-compromised patients nor to patients with infections requiring long-term antibiotic therapy, like endocarditis or osteomyelitis. Adapted from Salluh Crit Care 2014; 18:142 [74]. *Do not use CRP or PCT levels to guide decision to initiate antibiotic therapy