Inflammatory cytokine measurement quickly discriminates gram-negative from gram-positive bacteremia in pediatric hematology/oncology patients with septic shock
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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.
KeywordsCytokine Septic shock Gram-negative bacteremia Interleukin-10 Flow cytometry
- 2.Shime N, Kawasaki T, Saito O, Akamine Y, Toda Y, Takeuchi M, Sugimura H, Sakurai Y, Iijima M, Ueta I, Shimizu N, Nakagawa S (2012) Incidence and risk factors for mortality in paediatric severe sepsis: results from the national paediatric intensive care registry in Japan. Intensive Care Med 38:1191–1197PubMedCrossRefGoogle Scholar
- 7.Feezor RJ, Oberholzer C, Baker HV, Novick D, Rubinstein M, Moldawer LL, Pribble J, Souza S, Dinarello CA, Ertel W, Oberholzer A (2003) Molecular characterization of the acute inflammatory response to infections with gram-negative versus gram-positive bacteria. Infect Immun 71:5803–5813PubMedCrossRefGoogle Scholar
- 10.Lehrnbecher T, Venzon D, de Haas M, Chanock SJ, Kuhl J (1999) Assessment of measuring circulating levels of interleukin-6, interleukin-8, C-reactive protein, soluble Fc gamma receptor type III, and mannose-binding protein in febrile children with cancer and neutropenia. Clin Infect Dis 29:414–419PubMedCrossRefGoogle Scholar
- 13.Spasova MI, Terzieva DD, Tzvetkova TZ, Stoyanova AA, Mumdzhiev IN, Yanev IB, Genev ED (2005) Interleukin-6, interleukin-8, interleukin-10, and C-reactive protein in febrile neutropenia in children with malignant diseases. Folia Med (Plovdiv) 47:46–52Google Scholar
- 14.Prat C, Sancho JM, Dominguez J, Xicoy B, Gimenez M, Ferra C, Blanco S, Lacoma A, Ribera JM, Ausina V (2008) Evaluation of procalcitonin, neopterin, C-reactive protein, IL-6 and IL-8 as a diagnostic marker of infection in patients with febrile neutropenia. Leuk Lymphoma 49:1752–1761PubMedCrossRefGoogle Scholar
- 22.Tang Y, Liao C, Xu X, Song H, Shi S, Yang S, Zhao F, Xu W, Chen X, Mao J, Zhang L, Pan B (2011) Evaluation of Th1/Th2 cytokines as a rapid diagnostic tool for severe infection in paediatric haematology/oncology patients by the use of cytometric bead array technology. Clin Microbiol Infect 17:1666–1673PubMedCrossRefGoogle Scholar
- 26.Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL (2008) Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med 34:17–60PubMedCrossRefGoogle Scholar