Abstract Background Antimicrobial stewardship involves a delicate balance between the risk of undertreating individuals and the potential societal burden of overprescribing antimicrobials. However, early and accurate diagnosis of bacterial infections in critically ill patients is challenging, as the clinical manifestation is non-specific. Furthermore, the results from microbial cultures may be delayed, resulting in delayed antibiotic treatment, which is associated with increased mortality. Neutrophil activation is a major response to bacterial infection and calprotectin is the most abundant protein in the cytosolic fraction of neutrophils, shown as an early marker for neutrophil activation. The objective of this study was to evaluate the clinical performance of serum calprotectin in identifying bacterial infection in febrile infants presenting to an Emergency Department (ED) relative to other common biomarkers of infection. Methods 141 infants aged 28-90 days with suspected infectious disease presenting to the ED at The Hospital for Sick Children in Toronto, were included in this non-interventional investigation. All biomarkers except calprotectin were used in the routine clinical adjudication of the final diagnosis. Residual serum specimens collected as part of the standard care pathway were stored at -80°C prior to analysis of serum calprotectin using GCAL® assay (Gentian AS, Norway). Chart review was completed for key variables including, age (days), sex, chief complaint and temperature at ED presentation, and available laboratory test results (i.e., C-reactive protein and procalcitonin (Architect, Abbott Diagnostics), WBC count and neutrophil count (XN3000, Sysmex Europe GmbH), urinary leukocytes and nitrates, blood and/or urine bacterial culture). Final diagnosis, admission status, and antibiotic prescription at ED discharge were also extracted. Results Final discharge diagnosis in patient population included bacterial infection (n=23), viral infection (n=22), fever of unknown source (n=54) and other/unknown diagnosis (n=42). Antibiotics were prescribed in 36 cases, although bacterial infection could only be confirmed in 23 cases when final diagnosis was made. Statistically significant differences were observed in serum calprotectin (p<0.001), procalcitonin (p<0.001), and CRP (p<0.001) in patients with bacterial infections compared to patients with other discharge diagnoses. ROC curve analysis was performed for the identification of bacterial infections in the entire clinical cohort (n=141) and in only patients with laboratory confirmed bacterial or viral infection (n=41). Calprotectin and procalcitonin showed higher specificity than CRP and WBC count for differentiation between bacterial and viral infection in both cohorts. Performance of calprotectin in detection of bacterial infections was comparable to the performance of CRP, slightly better than performance of procalcitonin and superior to WBC count. Conclusions In this cohort, one third of the children that were prescribed antibiotics did not have confirmed bacterial infection. Hence, there is a need for adequate diagnostic tools to help discriminate between various kinds of infections. This study confirms serum calprotectin as a valuable biomarker for differentiation between types of infection and estimation of disease severity in febrile infants. Access to fast and accurate analysis of circulating calprotectin, combined with good clinical performance has the potential to make this biomarker a valuable complement to the current diagnostics of patients with bacterial infections and sepsis.
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Oct 4, 2024
Jordan Evans + 7
Open Access