Serum Calprotectin Levels and Inflammatory Biomarker Profiles in Adults with Culture-Confirmed Bacteremia

Background/Objectives: Circulating calprotectin reflects neutrophil and monocyte activation and has been proposed as a host-response biomarker in bacterial infection. However, its behavior in microbiologically confirmed bacteremia and its relationship with established inflammatory biomarkers remain incompletely defined. This exploratory study compared serum calprotectin and conventional inflammatory and hematological markers between adults with culture-confirmed bacteremia and controls without known comorbidities and examined calprotectin within the broader systemic inflammatory response associated with bacteremia. Methods: This prospective observational comparative study included 47 adults with culture-confirmed bacteremia and 30 controls without known comorbidities. Serum calprotectin, interleukin-6 (IL-6), C-reactive protein (CRP), procalcitonin, erythrocyte sedimentation rate (ESR), and hematological indices were compared between groups. Receiver operating characteristic (ROC) analyses were used descriptively to characterize between-group separation and were not intended to estimate clinical diagnostic accuracy. Hierarchical multivariable logistic regression was performed to assess the association between serum calprotectin and bacteremia after adjustment for age and sex. An extended model including the neutrophil-to-lymphocyte ratio (NLR), red cell distribution width–coefficient of variation (RDW-CV), and platelet count was considered exploratory. Gram-staining subgroups and 28-day outcomes were also examined. Results: Serum calprotectin concentrations were significantly higher in the bacteremia group than in controls (89.11 [80.16–95.35] vs. 62.90 [53.87–82.27] ng/mL; p < 0.001). Calprotectin showed an apparent area under the curve (AUC) of 0.840 (95% confidence interval [CI], 0.735–0.926), which was lower than those observed for IL-6, CRP, and procalcitonin. These ROC estimates reflect between-group separation within the present sample and should not be interpreted as estimates of diagnostic accuracy in patients with suspected infection. After adjustment for age and sex, each 10 ng/mL increase in calprotectin was associated with higher odds of belonging to the bacteremia group (adjusted odds ratio [aOR], 2.46; 95% CI, 1.58–3.85; p < 0.001). No biomarker significantly differentiated Gram-positive from Gram-negative bacteremia after false discovery rate (FDR) adjustment, and serum calprotectin was not associated with 28-day mortality. Conclusions: Serum calprotectin was elevated in adults with culture-confirmed bacteremia, consistent with activation of the systemic innate immune response. However, its apparent between-group discrimination was lower than that of IL-6, CRP, and procalcitonin, and it was not associated with Gram classification or 28-day mortality. Because the comparator group did not represent clinically similar patients undergoing evaluation for suspected infection, these findings should be interpreted as an exploratory characterization of the host response to bacteremia rather than as evidence of clinical diagnostic accuracy or added diagnostic value. Studies using clinically relevant comparator groups are needed to determine whether calprotectin provides incremental information beyond established biomarkers.