Biomarkers of Infection: Are They Useful in the ICU?

Abstract

Biomarkers are increasingly used in patients with serious infections in the critical care setting to complement clinical judgment and interpretation of other diagnostic and prognostic tests. The main purposes of such blood markers are (1) to improve infection diagnosis (i.e., differentiation between bacterial vs. viral vs. fungal vs. noninfectious), (2) to help in the early risk stratification and thus provide prognostic information regarding the risk for mortality and other adverse outcomes, and (3) to optimize antibiotic tailoring to individual needs of patients ("antibiotic stewardship").Especially in critically ill patients, in whom sepsis is a major cause of morbidity and mortality, rapid diagnosis is desirable to start timely and specific treatment.Besides some biomarkers, such as procalcitonin, which is well established and has shown positive effects in regard to utilization of antimicrobials and clinical outcomes, there is a growing number of novel markers from different pathophysiological pathways, where the final proof of an added value to clinical judgment and ultimately clinical benefit to patients is still lacking.Without a doubt, the addition of blood biomarkers to clinical medicine has had a strong impact on the way we care for patients today. Recent trials show that as an adjunct to other clinical and laboratory parameters these markers provide important information about risks for bacterial infection and resolution of infection. Moreover, biomarkers can help to optimize management of patients with serious illness in the intensive care unit, thereby offering more individualized treatment courses with overall improvements in clinical outcomes.

Fig. 1

Types of biomarkers and examples of their potential use.

Fig. 2

PCT use in patients with severe illness in the ICU. Note: caution in patients with immunosuppression (including HIV), cystic fibrosis, pancreatitis, trauma, pregnancy, high volume transfusion, malaria; PCT-guided stewardship should not be applied to patients with chronic infections (e.g., abscess, osteomyelitis, endocarditis). ICU, intensive care unit; PCT, procalcitonin. (Adapted from Schuetz et al. 21 )

Fig. 3

Immunological and nonimmunological response through biomarkers and mediators to a bacterial pathogen and the resulting multiorgan dysfunction. Biomarkers and their impact on organ function can help confirm a diagnosis, to assess the patients risk for mortality and morbidity as well as to tailor individual treatment. Once the source of infection is controlled due to adequate treatment, organ function can recover and biomarker abnormalities normalize. Otherwise biomarker abnormalities persist and leading to progredient organ failure and maybe death. aPTT, activated partial thromboplastin time; AT, antithrombin; BNP, B-type natriuretic peptide; CD14 and CD64, integral membrane glycoproteins; CRP, C-reactive protein; DIC, disseminated intravascular coagulation; IL, interleukin; NGAL, neutrophil gelatinase-associated lipocalin; PCT, procalcitonin; PT, prothrombin time; sTNF, soluble tumor necrosis factor; sTREM, soluble triggered receptor expressed on myeloid cells; suPAR, soluble urokinase type plasminogen activator receptor. (Adapted from Reinhart K. et al. New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev 2012;25(4):609–634.)