Skip to main content
NCBI home page
Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1995 May;33(5):1278–1282. doi: 10.1128/jcm.33.5.1278-1282.1995

Reappraisal with meta-analysis of bacteremia, endotoxemia, and mortality in gram-negative sepsis.

J C Hurley 1
PMCID: PMC228145  PMID: 7615741

Abstract

Among patients with suspected sepsis, endotoxemia is variably present in association with gram-negative bacteremia. A total of 738 patients with suspected sepsis from 11 studies could be classified into four groups: 131 (18%) patients had both endotoxemia and gram-negative bacteremia (group 1), 87 (12%) had only gram-negative bacteremia (group 2), and 143 (19%) had only endotoxemia (group 3); in 377 (51%) patients neither could be detected (group 4). By the statistical techniques of meta-analysis, the fatality risk for patients with either endotoxemia or gram-negative bacteremia or both was estimated with group-specific case fatality rates from these studies and expressed as an odds ratio (OR; 95% confidence interval [95% CI]) versus patients with these factors absent. This risk was increased marginally when endotoxemia was detected without gram-negative bacteremia (OR, 2.3; 95% CI, 1.3 to 4.0) or the converse (OR, 2.0; 95% CI, 1.0 to 3.8), in contrast to the striking increase when both endotoxemia and gram-negative bacteremia were detected (OR, 6.3; 95% CI, 4.0 to 10.0). Alone, neither endotoxemia nor gram-negative bacteremia is a strong predictor of outcome in patients with suspected sepsis. However, in combination, the two identify a subpopulation with a substantially increased risk of mortality.

Full Text

The Full Text of this article is available as a PDF (181.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersen B. M., Solberg O. Endotoxin liberation and invasivity of Neisseria meningitidis. Scand J Infect Dis. 1984;16(3):247–254. doi: 10.3109/00365548409070397. [DOI] [PubMed] [Google Scholar]
  2. Bland L. A., Villarino M. E., Arduino M. J., McAllister S. K., Gordon S. M., Uyeda C. T., Valdon C., Potts D., Jarvis W. R., Favero M. S. Bacteriologic and endotoxin analysis of salvaged blood used in autologous transfusions during cardiac operations. J Thorac Cardiovasc Surg. 1992 Mar;103(3):582–588. [PubMed] [Google Scholar]
  3. Brandtzaeg P., Kierulf P., Gaustad P., Skulberg A., Bruun J. N., Halvorsen S., Sørensen E. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J Infect Dis. 1989 Feb;159(2):195–204. doi: 10.1093/infdis/159.2.195. [DOI] [PubMed] [Google Scholar]
  4. Brock-Utne J. G., Gaffin S. L., Wells M. T., Gathiram P., Sohar E., James M. F., Morrell D. F., Norman R. J. Endotoxaemia in exhausted runners after a long-distance race. S Afr Med J. 1988 May 7;73(9):533–536. [PubMed] [Google Scholar]
  5. Butler T., Levin J., Do Quang C. u., Walker R. I. Bubonic plague: detection of endotoxemia with the limulus test. Ann Intern Med. 1973 Nov;79(5):642–646. doi: 10.7326/0003-4819-79-5-642. [DOI] [PubMed] [Google Scholar]
  6. Butler T., Levin J., Linh N. N., Chau D. M., Adickman M., Arnold K. Yersinia pestis infection in Vietnam. II. Quantiative blood cultures and detection of endotoxin in the cerebrospinal fluid of patients with meningitis. J Infect Dis. 1976 May;133(5):493–499. doi: 10.1093/infdis/133.5.493. [DOI] [PubMed] [Google Scholar]
  7. Casey W. F., Hauser G. J., Hannallah R. S., Midgley F. M., Khan W. N. Circulating endotoxin and tumor necrosis factor during pediatric cardiac surgery. Crit Care Med. 1992 Aug;20(8):1090–1096. doi: 10.1097/00003246-199208000-00004. [DOI] [PubMed] [Google Scholar]
  8. Danner R. L., Elin R. J., Hosseini J. M., Wesley R. A., Reilly J. M., Parillo J. E. Endotoxemia in human septic shock. Chest. 1991 Jan;99(1):169–175. doi: 10.1378/chest.99.1.169. [DOI] [PubMed] [Google Scholar]
  9. Danner R. L., Natanson C., Elin R. J., Hosseini J. M., Banks S., MacVittie T. J., Parrillo J. E. Pseudomonas aeruginosa compared with Escherichia coli produces less endotoxemia but more cardiovascular dysfunction and mortality in a canine model of septic shock. Chest. 1990 Dec;98(6):1480–1487. doi: 10.1378/chest.98.6.1480. [DOI] [PubMed] [Google Scholar]
  10. Das J., Schwartz A. A., Folkman J. Clearance of endotoxin by platelets: role in increasing the accuracy of the Limulus gelation test and in combating experimental endotoxemia. Surgery. 1973 Aug;74(2):235–240. [PubMed] [Google Scholar]
  11. Dofferhoff A. S., Bom V. J., de Vries-Hospers H. G., van Ingen J., vd Meer J., Hazenberg B. P., Mulder P. O., Weits J. Patterns of cytokines, plasma endotoxin, plasminogen activator inhibitor, and acute-phase proteins during the treatment of severe sepsis in humans. Crit Care Med. 1992 Feb;20(2):185–192. doi: 10.1097/00003246-199202000-00007. [DOI] [PubMed] [Google Scholar]
  12. Feldman S., Pearson T. A. The Limulus test and gram-negative bacillary sepsis. Am J Dis Child. 1974 Aug;128(2):172–174. doi: 10.1001/archpedi.1974.02110270046009. [DOI] [PubMed] [Google Scholar]
  13. Fossard D. P., Kakkar V. V. The Limulus test in experimental and clinical endotoxaemia. Br J Surg. 1974 Oct;61(10):798–804. doi: 10.1002/bjs.1800611013. [DOI] [PubMed] [Google Scholar]
  14. Harthug S., Bjorvatn B., Osterud B. Quantitation of endotoxin in blood from patients with meningococcal disease using a limulus lysate test in combination with chromogenic substrate. Infection. 1983 Jul-Aug;11(4):192–195. doi: 10.1007/BF01641194. [DOI] [PubMed] [Google Scholar]
  15. Hurley J. C. Concordance of endotoxemia with gram-negative bacteremia in patients with gram-negative sepsis: a meta-analysis. J Clin Microbiol. 1994 Sep;32(9):2120–2127. doi: 10.1128/jcm.32.9.2120-2127.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hurley J. C. Endotoxemia: methods of detection and clinical correlates. Clin Microbiol Rev. 1995 Apr;8(2):268–292. doi: 10.1128/cmr.8.2.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hurley J. C. Sepsis management and antiendotoxin therapy after nebacumab. A reappraisal. Drugs. 1994 Jun;47(6):855–861. doi: 10.2165/00003495-199447060-00001. [DOI] [PubMed] [Google Scholar]
  18. Koch T., Duncker H. P., Axt R., Schiefer H. G., van Ackern K., Neuhof H. Alterations of bacterial clearance induced by endotoxin and tumor necrosis factor. Infect Immun. 1993 Aug;61(8):3143–3148. doi: 10.1128/iai.61.8.3143-3148.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Levin J., Poore T. E., Young N. S., Margolis S., Zauber N. P., Townes A. S., Bell W. R. Gram-negative sepsis: detection of endotoxemia with the limulus test. With studies of associated changes in blood coagulation, serum lipids, and complement. Ann Intern Med. 1972 Jan;76(1):1–7. doi: 10.7326/0003-4819-76-1-1. [DOI] [PubMed] [Google Scholar]
  20. MANTEL N., HAENSZEL W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959 Apr;22(4):719–748. [PubMed] [Google Scholar]
  21. Martinez L. A., Quintiliani R., Tilton R. C. Clinical experience on the detection of endotoxemia with the limulus test. J Infect Dis. 1973 Jan;127(1):102–105. doi: 10.1093/infdis/127.1.102. [DOI] [PubMed] [Google Scholar]
  22. Mattsby-Baltzer I., Lindgren K., Lindholm B., Edebo L. Endotoxin shedding by enterobacteria: free and cell-bound endotoxin differ in Limulus activity. Infect Immun. 1991 Feb;59(2):689–695. doi: 10.1128/iai.59.2.689-695.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. McCartney A. C., Banks J. G., Clements G. B., Sleigh J. D., Tehrani M., Ledingham I. M. Endotoxaemia in septic shock: clinical and post mortem correlations. Intensive Care Med. 1983;9(3):117–122. doi: 10.1007/BF01772577. [DOI] [PubMed] [Google Scholar]
  24. Mege J. L., Sanguedolce M. V., Purgus R., Moulin B., Bongrand P., Capo C., Olmer M. Chronic and intradialytic effects of high-flux hemodialysis on tumor necrosis factor-alpha production: relationship to endotoxins. Am J Kidney Dis. 1992 Nov;20(5):482–488. doi: 10.1016/s0272-6386(12)70260-3. [DOI] [PubMed] [Google Scholar]
  25. Mellado M. C., Rodríguez-Contreras R., Fernandez-Crehuet M., Lopez-Gigosos R., Delgado Rodriguez M., Galvez-Vargas R. Endotoxin liberation by strains of N. meningitidis isolated from patients and healthy carriers. Epidemiol Infect. 1991 Apr;106(2):289–295. doi: 10.1017/s0950268800048433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shenep J. L., Flynn P. M., Barrett F. F., Stidham G. L., Westenkirchner D. F. Serial quantitation of endotoxemia and bacteremia during therapy for gram-negative bacterial sepsis. J Infect Dis. 1988 Mar;157(3):565–568. doi: 10.1093/infdis/157.3.565. [DOI] [PubMed] [Google Scholar]
  27. Stumacher R. J., Kovnat M. J., McCabe W. R. Limitations of the usefulness of the Limulus assay for endotoxin. N Engl J Med. 1973 Jun 14;288(24):1261–1264. doi: 10.1056/NEJM197306142882402. [DOI] [PubMed] [Google Scholar]
  28. Taveira da Silva A. M., Kaulbach H. C., Chuidian F. S., Lambert D. R., Suffredini A. F., Danner R. L. Brief report: shock and multiple-organ dysfunction after self-administration of Salmonella endotoxin. N Engl J Med. 1993 May 20;328(20):1457–1460. doi: 10.1056/NEJM199305203282005. [DOI] [PubMed] [Google Scholar]
  29. Thompson S. G., Pocock S. J. Can meta-analyses be trusted? Lancet. 1991 Nov 2;338(8775):1127–1130. doi: 10.1016/0140-6736(91)91975-z. [DOI] [PubMed] [Google Scholar]
  30. Wortel C. H., von der Möhlen M. A., van Deventer S. J., Sprung C. L., Jastremski M., Lubbers M. J., Smith C. R., Allen I. E., ten Cate J. W. Effectiveness of a human monoclonal anti-endotoxin antibody (HA-1A) in gram-negative sepsis: relationship to endotoxin and cytokine levels. J Infect Dis. 1992 Dec;166(6):1367–1374. doi: 10.1093/infdis/166.6.1367. [DOI] [PubMed] [Google Scholar]
  31. Yoshida M., Obayashi T., Tamura H., Tanaka S., Kawai T., Sakamoto S., Miura Y. Diagnostic and prognostic significance of plasma endotoxin determination in febrile patients with haematological malignancies. Eur J Cancer. 1994;30A(2):145–147. doi: 10.1016/0959-8049(94)90074-4. [DOI] [PubMed] [Google Scholar]
  32. Young L. S. Opsonizing antibodies, host factors, and the limulus assay for endotoxin. Infect Immun. 1975 Jul;12(1):88–92. doi: 10.1128/iai.12.1.88-92.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yusuf S., Peto R., Lewis J., Collins R., Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis. 1985 Mar-Apr;27(5):335–371. doi: 10.1016/s0033-0620(85)80003-7. [DOI] [PubMed] [Google Scholar]
  34. van Deventer S. J., Buller H. R., ten Cate J. W., Sturk A., Pauw W. Endotoxaemia: an early predictor of septicaemia in febrile patients. Lancet. 1988 Mar 19;1(8586):605–609. doi: 10.1016/s0140-6736(88)91412-2. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES