Lipopolysaccharide-binding Protein: a Possible Diagnostic Marker for Gram-negative Bacteremia in Neutropenic Cancer Patients

Overview

Journal Intensive Care Med

Specialty Critical Care

Date 2003 Oct 22

PMID 14569424

Citations 16

Authors

Claudi S M Oude Nijhuis

Edo Vellenga

Simon M G J Daenen

Winette T A van der Graaf

Jourik A Gietema

Harry J M Groen

Willem A Kamps

Eveline S J M de Bont

Affiliations

Soon will be listed here.

Abstract

Objective: Cancer patients with febrile neutropenia after chemotherapy have a variable risk of bacterial infection. Especially Gram-negative bacteremia is associated with high mortality and/or morbidity. Early diagnosis of patients with Gram-negative bacteremia at the onset of febrile neutropenia is potentially useful in tailoring therapy.

Design And Setting: Prospective study at the Department of Pediatric Oncology and Internal Medicine of a university hospital.

Patients: Were analyzed 66 febrile neutropenic episodes in 57 adults and children. Patients were divided into four groups: those with Gram-negative bacteremia, Gram-positive bacteremia, clinical sepsis, or fever of unknown origin.

Measurements And Results: Plasma lipopolysaccharide-binding protein (LBP) and C-reactive protein (CRP) concentrations were determined. LBP at the onset of febrile neutropenia was significantly higher in patients with Gram-negative bacteremia than those with fever of unknown origin and those with Gram-positive bacteremia. Using a cutoff value for LBP proved to have much greater sensitivity, specificity, and positive and negative predictive value for Gram-negative bacteremia than the best cutoff value for CRP.

Conclusions: An initial high LBP level might predict Gram-negative bacteremia in cancer patients with febrile neutropenia. These results may have potential clinical impact by allowing therapy to be initiated for these patients at a very early stage.

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References

Freifeld A, Marchigiani D, Walsh T, Chanock S, Lewis L, Hiemenz J . A double-blind comparison of empirical oral and intravenous antibiotic therapy for low-risk febrile patients with neutropenia during cancer chemotherapy. N Engl J Med. 1999; 341(5):305-11. DOI: 10.1056/NEJM199907293410501. View

Waage A, Remick D, Steinshamn S, Deforge L, Lamvik J . Interleukin 8 in serum in granulocytopenic patients with infections. Br J Haematol. 1994; 86(1):36-40. DOI: 10.1111/j.1365-2141.1994.tb03249.x. View

Vreugdenhil A, Snoek A, van t Veer C, Greve J, Buurman W . LPS-binding protein circulates in association with apoB-containing lipoproteins and enhances endotoxin-LDL/VLDL interaction. J Clin Invest. 2001; 107(2):225-34. PMC: 199173. DOI: 10.1172/JCI10832. View

Faure E, Equils O, Sieling P, Thomas L, Zhang F, Kirschning C . Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J Biol Chem. 2001; 275(15):11058-63. DOI: 10.1074/jbc.275.15.11058. View

Talcott J, Finberg R, Mayer R, Goldman L . The medical course of cancer patients with fever and neutropenia. Clinical identification of a low-risk subgroup at presentation. Arch Intern Med. 1988; 148(12):2561-8. View

Jack R, Fan X, Bernheiden M, Rune G, Ehlers M, Weber A . Lipopolysaccharide-binding protein is required to combat a murine gram-negative bacterial infection. Nature. 1997; 389(6652):742-5. DOI: 10.1038/39622. View

De Bont E, Vellenga E, Swaanenburg J, Fidler V, Kamps W . Plasma IL-8 and IL-6 levels can be used to define a group with low risk of septicaemia among cancer patients with fever and neutropenia. Br J Haematol. 1999; 107(2):375-80. DOI: 10.1046/j.1365-2141.1999.01707.x. View

Bodey G, Buckley M, SATHE Y, Freireich E . Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med. 1966; 64(2):328-40. DOI: 10.7326/0003-4819-64-2-328. View

Pizzo P . Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med. 1993; 328(18):1323-32. DOI: 10.1056/NEJM199305063281808. View

10.

Opal S, Scannon P, Vincent J, White M, Carroll S, Palardy J . Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock. J Infect Dis. 1999; 180(5):1584-9. DOI: 10.1086/315093. View

11.

Svaldi M, Hirber J, Lanthaler A, Mayr O, Faes S, Peer E . Procalcitonin-reduced sensitivity and specificity in heavily leucopenic and immunosuppressed patients. Br J Haematol. 2001; 115(1):53-7. DOI: 10.1046/j.1365-2141.2001.03083.x. View

12.

Yang R, Mark M, Gray A, Huang A, Xie M, Zhang M . Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Nature. 1998; 395(6699):284-8. DOI: 10.1038/26239. View

13.

. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992; 20(6):864-74. View

14.

Engel A, Mack E, Kern P, Kern W . An analysis of interleukin-8, interleukin-6 and C-reactive protein serum concentrations to predict fever, gram-negative bacteremia and complicated infection in neutropenic cancer patients. Infection. 1998; 26(4):213-21. DOI: 10.1007/BF02962366. View

15.

De Bont E, Vellenga E, Swaanenburg J, Kamps W . Procalcitonin: a diagnostic marker of bacterial infection in neutropenic cancer patients with fever?. Infection. 2001; 28(6):398-400. DOI: 10.1007/s150100070014. View

16.

Martin T, Rubenfeld G, Ruzinski J, GOODMAN R, Steinberg K, Leturcq D . 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. 1997; 155(3):937-44. DOI: 10.1164/ajrccm.155.3.9117029. View

17.

Sickles E, Greene W, Wiernik P . Clinical presentation of infection in granulocytopenic patients. Arch Intern Med. 1975; 135(5):715-9. View