Inflammatory cytokine measurement quickly discriminates gram-negative from gram-positive bacteremia in pediatric hematology/oncology patients with septic shock

Abstract

We performed a prospective study to evaluate the ability of inflammatory cytokines in discriminating gram-negative from gram-positive bacteremia in septic shock. During the study period, the serum inflammatory cytokine levels were measured at the onset of septic shock by flow cytometry in pediatric hematology/oncology patients with septic shock. One hundred episodes of septic shock were enrolled. Of 97 episodes of monomicrobial infection, 73.2 % were caused by gram-negative bacteremia and 26.8 % by gram-positive bacteremia. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were closely related to the pediatric index of mortality 2 (PIM2) score and mortality. However, although the PIM2 score and mortality were comparable, the IL-6, IL-10, and TNF-α levels were significantly higher in patients with gram-negative bacteremia (GNB) than those with gram-positive bacteremia (median levels, pg/mL: IL-6: 784.1 vs. 254.4, P = 0.001; IL-10: 192.2 vs. 19.7, P < 0.001; TNF-α: 4.2 vs. 2.0, P < 0.001). Of the three cytokines, IL-10 was the most useful biomarker for GNB prediction in the derivation cohort and a cutoff value of 50 pg/mL showed a sensitivity of 70.8 % and a specificity of 80.0 %, with a positive predictive value of 89.5 %. When this cutoff value was applied to the validation cohort, the sensitivity, specificity, and positive predictive value were 80.9, 75.0, and 90.5 %, respectively. Flow cytometry-based inflammatory cytokine measurement is a helpful adjuvant approach for early and quick discrimination of gram-negative from gram-positive bacteremia in pediatric hematology/oncology patients with septic shock which might be useful for evaluating the severity of shock and the selection and/or timely withdrawal or switch of antibiotics.