Skip to main content
Top
Published in: Intensive Care Medicine 6/2007

01-06-2007 | Pediatric Original

Lipopolysaccharide-binding protein, lipopolysaccharide, and soluble CD14 in sepsis of critically ill neonates and children

Authors: Maja Pavcnik-Arnol, Sergej Hojker, Metka Derganc

Published in: Intensive Care Medicine | Issue 6/2007

Login to get access

Abstract

Objective

To compare the diagnostic accuracy of lipopolysaccharide-binding protein (LBP) for sepsis in critically ill neonates and children with the two markers participating in the same inflammatory pathway, lipopolysaccharide and soluble CD14.

Design and setting

Prospective, observational study in a multidisciplinary neonatal and pediatric intensive care unit.

Patients

47 critically ill neonates and 49 critically ill children with systemic inflammatory response syndrome (SIRS) and suspected sepsis, classified into two groups: those with and those without sepsis.

Interventions

Serum LBP, lipopolysaccharide, soluble CD14, C-reactive protein, and procalcitonin were measured on 2 consecutive days. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and predictive values were evaluated.

Results

AUC for LBP on the first day of suspected infection was 0.97 in neonates aged under 48 h, 0.93 in neonates over 48 h and 0.82 in children. AUCs for lipopolysaccharide and soluble CD14 were 0.77 and 0.74 in neonates under 48 h, 0.53 and 0.76 in neonates over 48 h, and 0.72 and 0.53 in children. AUCs for procalcitonin and C-reactive protein were 0.65 and 0.89 in neonates under 48 h, 0.65 and 0.91 in neonates over 48 h, and 0.76 and 0.69 in children.

Conclusions

In critically ill neonates and children LBP concentration on the first day of suspected sepsis is a better marker of sepsis than lipopolysaccharide, soluble CD14, procalcitonin, and in neonates younger than 48 h and children, also a better marker than C-reactive protein. Lipopolysaccharide and soluble CD14 are not suitable markers for the differentiation of infectious and noninfectious SIRS.
Literature
1.
go back to reference Proulx F, Fayon M, Farrell C, Lacroix J, Gauthier M (1996) Epidemiology of sepsis and multiple dysfunction syndrome in children. Chest 109:1033–1037PubMed Proulx F, Fayon M, Farrell C, Lacroix J, Gauthier M (1996) Epidemiology of sepsis and multiple dysfunction syndrome in children. Chest 109:1033–1037PubMed
2.
go back to reference Turner D, Hammerman C, Rudensky B, Schlesinger Y, Goia C, Schimmel MS (2006) Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram. Arch Dis Child Fetal Neonatal Ed 91:F283–F286PubMedCrossRef Turner D, Hammerman C, Rudensky B, Schlesinger Y, Goia C, Schimmel MS (2006) Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram. Arch Dis Child Fetal Neonatal Ed 91:F283–F286PubMedCrossRef
3.
go back to reference Bonac B, Derganc M, Wraber B, Hojker S (2000) Interleukin-8 and procalcitonin in early diagnosis of early severe bacterial infection in critically ill neonates. Pflugers Arch [Suppl 5]440:R72–R74PubMedCrossRef Bonac B, Derganc M, Wraber B, Hojker S (2000) Interleukin-8 and procalcitonin in early diagnosis of early severe bacterial infection in critically ill neonates. Pflugers Arch [Suppl 5]440:R72–R74PubMedCrossRef
4.
go back to reference Blommendahl J, Janas M, Laine S, Miettinen A, Ashorn P (2002) Comparison of procalcitonin with CRP and differential white blood cell count for diagnosis of culture-proven neonatal sepsis. Scand J Infect Dis 34:620–622PubMedCrossRef Blommendahl J, Janas M, Laine S, Miettinen A, Ashorn P (2002) Comparison of procalcitonin with CRP and differential white blood cell count for diagnosis of culture-proven neonatal sepsis. Scand J Infect Dis 34:620–622PubMedCrossRef
5.
go back to reference Pavcnik-Arnol M, Hojker S, Derganc M (2004) Lipopolysaccharide-binding protein in critically ill neonates and children with suspected infection: comparison with procalcitonin, interleukin-6, and C-reactive protein. Intensive Care Med 30:1454–1460PubMedCrossRef Pavcnik-Arnol M, Hojker S, Derganc M (2004) Lipopolysaccharide-binding protein in critically ill neonates and children with suspected infection: comparison with procalcitonin, interleukin-6, and C-reactive protein. Intensive Care Med 30:1454–1460PubMedCrossRef
6.
go back to reference Lopez Sastre JB, Perez Solis D, Roques Serradilla V, Fernandez Colomer B, Coto Cotallo GD, Vidal XK, Narabona Lopez E, Garcia del Rio M, Sanchez Luna M, Belaustegui Cueto A, Moro Serrano M, Urbon Artero A, Alvaro Iglesias E, Cotero Lavin A, Martinez Vilalta E, Jimenez Cobos B, Grupo de Hospitales Castrillo (2006) Procalcitonin is not sufficiently reliable to be the sole marker of neonatal sepsis of nosocomial origin. BMC Pediatrics 6:16–22PubMedCrossRef Lopez Sastre JB, Perez Solis D, Roques Serradilla V, Fernandez Colomer B, Coto Cotallo GD, Vidal XK, Narabona Lopez E, Garcia del Rio M, Sanchez Luna M, Belaustegui Cueto A, Moro Serrano M, Urbon Artero A, Alvaro Iglesias E, Cotero Lavin A, Martinez Vilalta E, Jimenez Cobos B, Grupo de Hospitales Castrillo (2006) Procalcitonin is not sufficiently reliable to be the sole marker of neonatal sepsis of nosocomial origin. BMC Pediatrics 6:16–22PubMedCrossRef
7.
go back to reference Casado-Flores J, Blanco-Quiros A, Asensio J, Arranz E, Garrote JA, Nieto M (2003) Serum procalcitonin in children with suspected sepsis: a comparison with C-reactive protein and neutrophil count. Ped Crit Care Med 4:190–195CrossRef Casado-Flores J, Blanco-Quiros A, Asensio J, Arranz E, Garrote JA, Nieto M (2003) Serum procalcitonin in children with suspected sepsis: a comparison with C-reactive protein and neutrophil count. Ped Crit Care Med 4:190–195CrossRef
8.
go back to reference Arkader R, Troster EJ, Lopes MR, Junior RR, Carcillo JA, Leone C, Okay TS (2006) Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome. Arch Dis Child 91:117–120PubMedCrossRef Arkader R, Troster EJ, Lopes MR, Junior RR, Carcillo JA, Leone C, Okay TS (2006) Procalcitonin does discriminate between sepsis and systemic inflammatory response syndrome. Arch Dis Child 91:117–120PubMedCrossRef
9.
go back to reference Zweigner J, Schumann RR, Weber JR (2006) The role of lipopolysaccharide-binding protein in modulating the innate immune response. Microb Infect 8:946–952CrossRef Zweigner J, Schumann RR, Weber JR (2006) The role of lipopolysaccharide-binding protein in modulating the innate immune response. Microb Infect 8:946–952CrossRef
10.
go back to reference Opal SM, Scannon PJ, Vincent JL, White M, Carroll SF, Palardy JE, Parejo NA, Pribble JP, Lemke JH (1999) Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock. J Infect Dis 180:1584–1589PubMedCrossRef Opal SM, Scannon PJ, Vincent JL, White M, Carroll SF, Palardy JE, Parejo NA, Pribble JP, Lemke JH (1999) Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock. J Infect Dis 180:1584–1589PubMedCrossRef
11.
go back to reference Blairon L, Wittebole X, Laterre PF (2003) Lipopolysaccharide-binding protein serum levels in patients with severe sepsis due to gram-positive and fungal infections. J Infect Dis 187:287–291PubMedCrossRef Blairon L, Wittebole X, Laterre PF (2003) Lipopolysaccharide-binding protein serum levels in patients with severe sepsis due to gram-positive and fungal infections. J Infect Dis 187:287–291PubMedCrossRef
12.
go back to reference Berner R, Furll B, Stelter F, Drose J, Muller HP, Schutt C (2002) Elevated levels of lipopolysaccharide-binding protein and soluble CD14 in plasma in neonatal early-onset sepsis. Clin Diagn Lab Immunol 9:440–445PubMedCrossRef Berner R, Furll B, Stelter F, Drose J, Muller HP, Schutt C (2002) Elevated levels of lipopolysaccharide-binding protein and soluble CD14 in plasma in neonatal early-onset sepsis. Clin Diagn Lab Immunol 9:440–445PubMedCrossRef
13.
go back to reference Behrendt D, Dembinski J, Heep A, Bartman P (2004) Lipopolysaccharide binding protein in preterm infants. Arch Dis Child Fetal Neonatal Ed 89:F551–F554PubMedCrossRef Behrendt D, Dembinski J, Heep A, Bartman P (2004) Lipopolysaccharide binding protein in preterm infants. Arch Dis Child Fetal Neonatal Ed 89:F551–F554PubMedCrossRef
14.
go back to reference Orlikowsky TW, Trug C, Neunhoeffer F, Deperschmidt M, Eichner M, Poets CF (2006) Lipopolysaccharide-binding protein in noninfected neonates and those with suspected early-onset bacterial infection. J Perinatol 26:115–119PubMedCrossRef Orlikowsky TW, Trug C, Neunhoeffer F, Deperschmidt M, Eichner M, Poets CF (2006) Lipopolysaccharide-binding protein in noninfected neonates and those with suspected early-onset bacterial infection. J Perinatol 26:115–119PubMedCrossRef
15.
go back to reference Triantafilou M, Triantafilou K (2005) The dynamics of LPS recognition: complex orchestration of multiple receptors. J Endotoxin Res 11:5–11PubMed Triantafilou M, Triantafilou K (2005) The dynamics of LPS recognition: complex orchestration of multiple receptors. J Endotoxin Res 11:5–11PubMed
16.
go back to reference Scheifele DW, Melton P, Whitchelo V (1981) Evaluation of the Limulus test for endotoxemia in neonates with suspected sepsis. J Pediatr 98:899–903PubMedCrossRef Scheifele DW, Melton P, Whitchelo V (1981) Evaluation of the Limulus test for endotoxemia in neonates with suspected sepsis. J Pediatr 98:899–903PubMedCrossRef
17.
go back to reference Blanco A, Solis G, Arranz E, Coto GD, Ramos A, Telleria (1996) Serum levels of CD14 in neonatal sepsis by Gram-positive and Gram-negative bacteria. Acta Paediatr 85:728–732PubMed Blanco A, Solis G, Arranz E, Coto GD, Ramos A, Telleria (1996) Serum levels of CD14 in neonatal sepsis by Gram-positive and Gram-negative bacteria. Acta Paediatr 85:728–732PubMed
18.
go back to reference Pavcnik-Arnol M, Hojker S, Derganc M (2006) Lipopolysaccharide-binding protein in critically ill children with suspected infection: comparison with lipopolysaccharide, soluble CD14, procalcitonin, and C-reactive protein. In: Book of abstracts of European Academy of Paediatrics; 2006 Oct 7–10, Barcelona. Barcelona: Kenes, p 62 Pavcnik-Arnol M, Hojker S, Derganc M (2006) Lipopolysaccharide-binding protein in critically ill children with suspected infection: comparison with lipopolysaccharide, soluble CD14, procalcitonin, and C-reactive protein. In: Book of abstracts of European Academy of Paediatrics; 2006 Oct 7–10, Barcelona. Barcelona: Kenes, p 62
19.
go back to reference Goldstein B, Giroir B, Randolph A, the Members of the International Consensus Conference on Pediatric Sepsis (2005) International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6:2–8PubMedCrossRef Goldstein B, Giroir B, Randolph A, the Members of the International Consensus Conference on Pediatric Sepsis (2005) International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6:2–8PubMedCrossRef
20.
go back to reference Pollack MM, Patel KM, Ruttimann UE (1996) PRISM III: An updated Pediatric Risk of Mortality score. Crit Care Med 24:743–752PubMedCrossRef Pollack MM, Patel KM, Ruttimann UE (1996) PRISM III: An updated Pediatric Risk of Mortality score. Crit Care Med 24:743–752PubMedCrossRef
21.
go back to reference Tobias PS, Soldau K, Ulevitch RJ (1986) Isolation of a lipopolysaccharide-binding acute-phase reactant from rabbit serum. J Exp Med 164:777–793PubMedCrossRef Tobias PS, Soldau K, Ulevitch RJ (1986) Isolation of a lipopolysaccharide-binding acute-phase reactant from rabbit serum. J Exp Med 164:777–793PubMedCrossRef
22.
go back to reference Prucha M, Herold I, Zazula R, Dubska L, Dostal M, Hildebrand T, Hyanek J (2003) Significance of lipopolysaccharide-binding protein (an acute phase protein) in monitoring critically ill patients. Crit Care 7:R154–R159PubMedCrossRef Prucha M, Herold I, Zazula R, Dubska L, Dostal M, Hildebrand T, Hyanek J (2003) Significance of lipopolysaccharide-binding protein (an acute phase protein) in monitoring critically ill patients. Crit Care 7:R154–R159PubMedCrossRef
23.
go back to reference Gaini S, Koldkjaer OG, Pedersen C, Pedersen SS (2006) Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in community-acquired infections and sepsis: a prospective study. Crit Care 10:R53–R62PubMedCrossRef Gaini S, Koldkjaer OG, Pedersen C, Pedersen SS (2006) Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in community-acquired infections and sepsis: a prospective study. Crit Care 10:R53–R62PubMedCrossRef
24.
go back to reference Myc A, Buck J, Gonin J, Reynolds B, Hammerling U, Emanuel D (1997) The level of lipopolysaccharide-binding protein is significantly increased in plasma in patients with the systemic inflammatory response syndrome. Clin Diagn Lab Immunol 4:113–116PubMed Myc A, Buck J, Gonin J, Reynolds B, Hammerling U, Emanuel D (1997) The level of lipopolysaccharide-binding protein is significantly increased in plasma in patients with the systemic inflammatory response syndrome. Clin Diagn Lab Immunol 4:113–116PubMed
25.
go back to reference Takeshita S, Tsujimoto H, Kawase H, Kawamura Y, Sekine I (2002) Increased levels of lipopolysaccharide binding protein in plasma in children with Kawasaki disease. Clin Diagn Lab Immunol 9:205–206PubMedCrossRef Takeshita S, Tsujimoto H, Kawase H, Kawamura Y, Sekine I (2002) Increased levels of lipopolysaccharide binding protein in plasma in children with Kawasaki disease. Clin Diagn Lab Immunol 9:205–206PubMedCrossRef
26.
go back to reference Bortolussi R, Rajaraman K, Qing G, Rajaraman R (1997) Fibronectin enhances in vitro lipopolysaccharide priming of polymorphonuclear leukocytes. Blood 89:4182–4189PubMed Bortolussi R, Rajaraman K, Qing G, Rajaraman R (1997) Fibronectin enhances in vitro lipopolysaccharide priming of polymorphonuclear leukocytes. Blood 89:4182–4189PubMed
27.
go back to reference Yaegashi Y, Shirakawa K, Sato N, Suzuki Y, Kojika M, Imai S, Takahashi G, Miyata M, Furusako S, Endo S (2005) Evaluation of a newly identified soluble CD14 subtype as a marker of sepsis. J Infect Chemother 11:234–238PubMedCrossRef Yaegashi Y, Shirakawa K, Sato N, Suzuki Y, Kojika M, Imai S, Takahashi G, Miyata M, Furusako S, Endo S (2005) Evaluation of a newly identified soluble CD14 subtype as a marker of sepsis. J Infect Chemother 11:234–238PubMedCrossRef
28.
go back to reference Cohen J (2000) The detection and interpretation of endotoxaemia. Intensive Care Med 26:S51–S56PubMedCrossRef Cohen J (2000) The detection and interpretation of endotoxaemia. Intensive Care Med 26:S51–S56PubMedCrossRef
29.
go back to reference Martin TR, Rubenfeld GD, Ruzinski JT, Goodman RB, Steinberg KP, Leturcq DJ, Moriarty AM, Raghu G, Baughman RP, Hudson LD (1997) Relationship between soluble CD14, lipopolysaccharide binding protein, and the alveolar inflammatory response in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 155:937–944PubMed Martin TR, Rubenfeld GD, Ruzinski JT, Goodman RB, Steinberg KP, Leturcq DJ, Moriarty AM, Raghu G, Baughman RP, Hudson LD (1997) Relationship between soluble CD14, lipopolysaccharide binding protein, and the alveolar inflammatory response in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med 155:937–944PubMed
30.
go back to reference Bas S, Gauthier BR, Spenato U, Stingelin S, Gabay C (2004) CD14 is an acute-phase protein. J Immunol 172:4470–4479PubMed Bas S, Gauthier BR, Spenato U, Stingelin S, Gabay C (2004) CD14 is an acute-phase protein. J Immunol 172:4470–4479PubMed
31.
go back to reference Scott Watson R, Carcillo JA (2005) Scope and epidemiology of pediatric sepsis. Pediatr Crit Care Med [Suppl]6:S3–S5PubMedCrossRef Scott Watson R, Carcillo JA (2005) Scope and epidemiology of pediatric sepsis. Pediatr Crit Care Med [Suppl]6:S3–S5PubMedCrossRef
32.
go back to reference Resch B, Gusenleitner W, Muller WD (2003) Procalcitonin and interleukin-6 in the diagnosis of early-onset sepsis of the neonate. Acta Paediatr 92:243–245PubMedCrossRef Resch B, Gusenleitner W, Muller WD (2003) Procalcitonin and interleukin-6 in the diagnosis of early-onset sepsis of the neonate. Acta Paediatr 92:243–245PubMedCrossRef
33.
go back to reference Kitchens RL, Thompson PA (2003) Impact of sepsis-induced changes in plasma on LPS interactions with monocytes and plasma lipoproteins: roles of soluble CD14, LBP, and acute phase lipoproteins. J Endotoxin Res 9:113–118PubMed Kitchens RL, Thompson PA (2003) Impact of sepsis-induced changes in plasma on LPS interactions with monocytes and plasma lipoproteins: roles of soluble CD14, LBP, and acute phase lipoproteins. J Endotoxin Res 9:113–118PubMed
34.
go back to reference Lequier LL, Nikaidoh H, Leonard SR, Bokovoy JL, White ML, Scannon PJ, Giroir BP (2000) Preoperative and postoperative endotoxemia in children with congenital heart disease. Chest 117:1706–1712PubMedCrossRef Lequier LL, Nikaidoh H, Leonard SR, Bokovoy JL, White ML, Scannon PJ, Giroir BP (2000) Preoperative and postoperative endotoxemia in children with congenital heart disease. Chest 117:1706–1712PubMedCrossRef
35.
go back to reference Bolke E, Jehle PM, Trautmann M, Gotz I, Krebs B, Steinbach G, Orth K (2002) Different acute-phase response in newborns and infants undergoing surgery. Pediatr Res 51:333–338PubMedCrossRef Bolke E, Jehle PM, Trautmann M, Gotz I, Krebs B, Steinbach G, Orth K (2002) Different acute-phase response in newborns and infants undergoing surgery. Pediatr Res 51:333–338PubMedCrossRef
36.
go back to reference Holmlund U, Hoglind A, Larsson AK, Nilsson C, Sverremark Ekstrom E (2003) CD14 and developmet of atopic disease at 2 years of age in children with atopic or non-atopic mothers. Clin Exp Allergy 33:455–463PubMedCrossRef Holmlund U, Hoglind A, Larsson AK, Nilsson C, Sverremark Ekstrom E (2003) CD14 and developmet of atopic disease at 2 years of age in children with atopic or non-atopic mothers. Clin Exp Allergy 33:455–463PubMedCrossRef
37.
go back to reference Takeshita S, Nakatani K, Tsujimoto H, Kawamura Y, Kawase H, Sekine I (2000) Increased levels of circulating soluble CD14 in Kawasaki disease. Clin Exp Immunol 119:376–381PubMedCrossRef Takeshita S, Nakatani K, Tsujimoto H, Kawamura Y, Kawase H, Sekine I (2000) Increased levels of circulating soluble CD14 in Kawasaki disease. Clin Exp Immunol 119:376–381PubMedCrossRef
38.
go back to reference Carrillo EH, Gordon L, Goode E, Davis E, Polk HC (2001) Early elevation of soluble CD14 may help identify trauma patients at high risk for infection. J Trauma 50:810–816PubMedCrossRef Carrillo EH, Gordon L, Goode E, Davis E, Polk HC (2001) Early elevation of soluble CD14 may help identify trauma patients at high risk for infection. J Trauma 50:810–816PubMedCrossRef
39.
go back to reference Marshall JC, Foster D, Vincent JL, Cook DJ, Cohen J, Dellinger RP, Opal S, Abraham E, Brett SJ, Smith T, Mehta S, Derzko A, Romaschin A (2004) Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis 190:527–534PubMedCrossRef Marshall JC, Foster D, Vincent JL, Cook DJ, Cohen J, Dellinger RP, Opal S, Abraham E, Brett SJ, Smith T, Mehta S, Derzko A, Romaschin A (2004) Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis 190:527–534PubMedCrossRef
Metadata
Title
Lipopolysaccharide-binding protein, lipopolysaccharide, and soluble CD14 in sepsis of critically ill neonates and children
Authors
Maja Pavcnik-Arnol
Sergej Hojker
Metka Derganc
Publication date
01-06-2007
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 6/2007
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-007-0626-y

Other articles of this Issue 6/2007

Intensive Care Medicine 6/2007 Go to the issue