Calprotectin - Bacterial Marker | World Antibiotic Awarness Week 2019
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World Antibiotic Awareness Week 2019

antibiotic awareness - calprotectin

World Antibiotic Awareness Week 2019

Each November, World Antibiotic Awareness Week (WAAW) aims to increase global awareness of antibiotic resistance and to encourage best practices among the general public, health workers and policy makers to avoid the further emergence and spread of antibiotic resistance [1].

Better diagnostic biomarkers to avoid antibiotic overuse

The correct distinction between acute viral and bacterial infections is a major clinical challenge. Treating misclassified viral infections with antibiotics leads to unnecessary use of antibiotics. The increasing problem with antibiotic resistant bacteria further stresses the need of improved diagnostic markers that can effectively and precisely distinguish between bacterial and viral infections.

Neutrophils – bacterial infections marker

Activation of neutrophils is one of the earliest responses to bacterial infection. As part of the body’s defence against bacteria, the neutrophil granulocytes are activated [2].

The neutrophil granulocytes attack the invading bacteria by releasing its cytosol at the site of infection. In this process a wide range of proteins may be released into the blood stream [3]. These proteins, including calprotectin, can be used as biomarkers for activation of neutrophil granulocytes.

Calprotectin is released into the blood circulation upon neutrophil activation due to bacterial infection. It is one of the most abundant proteins in the cytosol of neutrophils, accounting for 40-50% of the total protein content [4, 5, 6].

antibiotic awareness - calprotectin

Calprotectin – a novel test for differentiating bacterial from viral infections

Because neutrophils are activated early in the course of an infection, calprotectin has the potential to be an early biomarker for bacterial infections. An important example is the recent study that shows that calprotectin increases within the first 2-3 hours after in vitro exposure to E. coli and endotoxins [7].

As previously shown for another neutrophil activation marker, human neutrophil lipocalin, calprotectin can therefore, in theory, be able to distinguish better between bacterial and viral infections than for example C-reactive protein (CRP) [8] and support more informed treatment decisions for antibiotic stewardship.

Calprotectin levels in bacterial sepsis

Plasma/serum calprotectin appears to be a useful early marker of bacterial infections in critically ill patients, with better predictive characteristics than white blood cell count (WBC) and procalcitonin (PCT) [9]. It has therefore been found to be a promising biomarker for sepsis in several studies performed in the last five years [9, 10, 11, 12, 13].

In one of the studies [13] the level of calprotectin in 66 patients with bacterial sepsis, was compared to the level in 24 patients with viral infections and 26 healthy controls. The study results showed significantly higher levels of calprotectin in patients with bacterial sepsis compared to patients with viral infections [p<0.05] and healthy controls [p<0.001].

Bartokova et al

Fig. 1 Bartakova et al (2019) [13]

 

As shown figure 1 above Bartáková et al [13] demonstrates that at the time of admission, the calprotectin serum levels were significantly higher in the bacterial sepsis group than in the viral infection group (and the healthy controls group).

The receiver operating characteristic (ROC) analysis showed that the ability to discriminate between bacterial sepsis and viral infection resulted in an area under the curve (AUC) value of 90.97 [13].

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A more selective use of antibiotics

Rapid determination of calprotectin, which is possible with a turbidimetric calprotectin immunoassay, can be an improvement in the management of infections. The scientific results presented above suggest that calprotectin can confirm the presence of bacterial infections and distinguish these from acute viral infections, especially in critical ill patients, which can be valuable as a tool in antibiotic stewardship.

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references

[1] https://www.who.int/news-room/events/detail/2019/11/18/default-calendar/world-antibiotic-awareness-week-2019

[2] Mantovani et al (2011). Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. Jul 25;11(8):519-31

[3] Bjarli et al (1998). “Blodet Og Kroppens Forsvarssystem.” In Menneskekroppen Fysiologi Og Anatomi. Gyldendal Akademisk. 268–97

[4] Dale et al (1983). “Purification and Partial Characterization of a Highly Immunogenic Human Leukocyte Protein, the L1 Antigen.” European Journal of Biochemistry / FEBS 134 (1): 1–6

[5] Striz et al (2004). Calprotectin – a pleiotropic molecule in acute and chronic inflammation. Physiol Res. 53(3):245-53

[6] Voganatsi et al (2001). Mechanism of extracellular release of human neutrophil calprotectin complex. J. Leukoc. Biol. 70 (1), 130 –134

[7] Lipcsey et al (2019). The time course of calprotectin liberation from human neutrophil granulocytes after Escherichia coli and endotoxin challenge. Innate Immun. Aug;25(6):369-373

[8] Xu et al (1995). Serum measurements of human neutrophil lipocalin (HNL) discriminate between acute bacterial and viral infections. Scand J Clin Lab Invest. Apr;55(2):125-31

[9] Jonsson et al (2017). Calprotectin as an early biomarker of bacterial infections in critically ill patients: an exploratory cohort assessment. Critical Care and Resuscitation, Volume 19 Number 3

[10] Gao et al (2015). Diagnostic and prognostic value of myeloid-related protein complex 8/14 for sepsis. Am J Emerg Med. Sep;33(9):1278-82

[11] Huang et al (2016). Serum Calprotectin Expression as a Diagnostic Marker for Sepsis in Postoperative Intensive Care Unit Patients. J Interferon Cytokine Res 36(10):607-16

[12] Simm et al (2016). Performance of plasma calprotectin as a biomarker of early sepsis: a pilot study. Biomark Med 10(8):811-8

[13] Bartáková et al (2019). Calprotectin and calgranulin C serum levels in bacterial sepsis. Diagn Microbiol Infect Dis. Mar;93(3):219-226

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