Serum biomarkers to differentiate Gram-negative, Gram-positive and fungal infection in febrile patients

Introduction. Contamination of specimens and overuse of broad spectrum antibiotics contribute to false positives and false negatives, respectively. Therefore, useful and applicable biomarkers of bacteremia are still required. Hypothesis/Gap Statement. IL-6 can be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. Aim. We aimed to evaluate the diagnostic efficiency of neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT) and interleukin-6 (IL-6) in discriminating Gram-negative (G − ) bacteria from Gram-positive (G + ) bacteria and fungi in febrile patients. Methodology. A total of 567 patients with fever were evaluated. Serum levels of IL-6, PCT, NLR and CRP were compared among a G − group ( n =188), a G + group ( n =168), a fungal group ( n =38) and a culture negative group ( n =173). Sensitivity, specificity, Yuden’s index and area under the Receiver operating characteristic (ROC) curve (AUC) were obtained to analyse the diagnostic abilities of these biomarkers in discriminating bloodstream infection caused by different pathogens. Results. Serum IL-6 and PCT in the G − group increased significantly when compared with both the G + group and fungal group ( P <0.05). AUC of IL-6 (0.767, 95 % CI:0.725–0.805) is higher than AUC of PCT (0.751, 95 % CI:0.708–0.796) in discriminating the G − group from G + group. When discriminating the G − group from fungal group, the AUC of IL-6 (0.695, 95 % CI:0.651–0.747) with a cut-off value of 464.3 pg ml −1 was also higher than the AUC of PCT (0.630, 95 % CI:0.585–0.688) with a cut-off value of 0.68 ng ml −1 . Additionally, AUC of NLR (0.685, 95 % CI:0.646–0.727) in discriminating the fungal group from G + group at the cut-off value of 9.03, was higher than AUC of IL-6, PCT and CRP. Conclusion. This study suggests that IL-6 could be used as a serum biomarker to discriminate among bacterial infections and fungal infections in febrile patients with a bloodstream infection. In addition, NLR is valuable to discriminate fungal infections from Gram-positive infections in febrile patients with a bloodstream infection.