Endotoxemia and Bacteremia in Patients With Sepsis Syndrome in the Intensive Care Unit

Guidet, Bertrand; Barakett, V.; Vassal, T.; Petit, J. C.; Offenstadt, G.

doi:10.1378/chest.106.4.1194

Cited by 71 publications

(46 citation statements)

References 34 publications

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“…Considering that co-exposure to TLR agonists and FRT is likely to occur in human sepsis (31,32), the results of this study suggest a possible positive feedback amplification pathway that may contribute to severe sepsis (Fig. 8).…”

Section: Discussionmentioning

confidence: 82%

Toll-like Receptor Agonists and Febrile Range Hyperthermia Synergize to Induce Heat Shock Protein 70 Expression and Extracellular Release

Gupta¹,

Cooper²,

Tulapurkar³

et al. 2013

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 82%

Toll-like Receptor Agonists and Febrile Range Hyperthermia Synergize to Induce Heat Shock Protein 70 Expression and Extracellular Release

Gupta¹,

Cooper²,

Tulapurkar³

et al. 2013

Journal of Biological Chemistry

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“…h Total excluding studies with ND 108 (44) 137 (56) 59 (60) 40 (40) Total all studies 142 (49) 144 (51) 66 (62) 41 (38) a The following bacteria causing bacteremia (with numbers of Limulus amebocyte lysate-positive patients and the total numbers of patients) from 17 studies (2,9,10,11,17,22,23,34,37,39,41,52,54,57,58,59,61) are not included in this analysis: N. meningitides (six of six), Salmonella species (seven of nine), Enterobacter species (13 of 33), and Haemophilus influenzae (eight of nine). ND, no data.…”

Section: (55)mentioning

confidence: 99%

Diagnosis of Endotoxemia with Gram-Negative Bacteremia Is Bacterial Species Dependent: a Meta-Analysis of Clinical Studies

Hurley

2009

J Clin Microbiol

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Endotoxemia is undetectable for up to 60% of cases of bacteremia caused by gram-negative (GN) species, a discordance attributed to the limitations of the Limulus assay for endotoxemia. The lipid A structure of the endotoxin molecule is critical for the sensing of GN bacteria by the host immune system although not so for sensing by the Limulus assay. The lipid A structure of commensal Enterobacteriaceae is hexa-acyl, whereas non-Enterobacteriaceae have a broader range of structures. By using a previously published classification of lipid A structures (R. . This finding is consistent across all the unrestricted studies, even including studies with seemingly contrary results for endotoxemia diagnosis among cases of bacteremia caused by GN bacteria overall. Surprisingly, with bacteremia caused by commensal Enterobacteriaceae, the diagnosis of endotoxemia appears to be unrelated to the Limulus assay sensitivity. Across these 45 studies, the association of endotoxemia with GN bacteremia is variable but consistent for different types of GN bacteremia.There are key structural differences between the lipid A components of the endotoxin molecule (lipopolysaccharide) of different gram-negative (GN) bacteria. Members of the Enterobacteriaceae characteristically have a lipid A structure with a hexa-acyl structure, whereas other lipid A structures are present for non-Enterobacteriaceae (45). These differences in lipid A structure are now known to be critically important for the recognition of GN bacteremia by the host immune system (45) by the MD-2-Toll-like receptor 4 receptor but not for sensing by the clotting proteins of the blood cells of the Limulus polyphemus horseshoe crab, from which the Limulus amebocyte lysate assay is derived (56). If the recognition of hexaacyl lipid A by the host immune system has a role in the pathogenesis of bacteremia, it might be expected that the proportion with detectable endotoxemia among patients with GN bacteremia might depend on the lipid A structure of the isolate.Attempts to define the concordance between GN bacteremia and endotoxemia in patients with sepsis have been elusive. Indeed, two of those studies (15, 54), with over a hundred patients each, concluded that there is no concordance. The purpose of this review is to attempt to reconcile the disparate findings from studies of clinically detected sepsis by examining the proportion with endotoxemia detected by using the Limulus assay for patients with different types of GN bacteremia for which the lipid A structures are known. Of particular interest is the proportion with endotoxemia among cases of bacteremia caused by commensal Enterobacteriaceae versus non-Enterobacteriaceae. The statistical techniques of meta-analysis are used to derive study-specific and summary estimates of these proportions expressed as an OR and more so to obtain estimates of the consistency in these ORs across the panel of studies (24). MATERIALS AND METHODS Data sources.A comprehensive search of the literature from 1966 to April 2009 was performed by using...

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“…Eight unrestricted studies [12,14,15,16,17,34,35,36] undertaken in an ICU setting were identified reporting the results for a total of 233 GN bacteremic patients of which 76 (33%) had a fatal outcome (table 1). In these studies E. coli was the most common GN bacteremia and had the least mortality (107 with 27 deaths; 25%), versus non- E. coli Enterobacteriaceae (75 with 26 deaths; 35%) and versus non-Enterobacteriaceae (51 with 23 deaths; 45%).…”

Section: Resultsmentioning

confidence: 99%

“…On the one hand, studies of patients with plague [7,8], or meningococcemia [9], have found a quantitative correlation between the level of endotoxemia and the degree of organ dysfunction or mortality. On the other hand, larger studies of sepsis in which the type of GN bacteremias were not restricted to any specific GN species type [10,11,12,13,14,15,16,17,18,19,20], have generated findings that were contradictory. In aggregate, the results from these studies indicate that endotoxemia detection is a borderline predictor of mortality risk (odds ratio <2) [4,21].…”

Section: Introductionmentioning

confidence: 99%

Prognostic Value of Endotoxemia in Patients with Gram-Negative Bacteremia Is Bacterial Species Dependent

Hurley

Opal²

2013

J Innate Immun

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The prognostic impact of endotoxemia detection in sepsis is unclear. Endotoxemia is detectable in <70% of patients with Gram-negative (GN) bacteremias. Mortality proportion data were available from 27 published studies of patients with GN bacteremia in various settings. Among ten studies restricted to specific types of GN bacteremia, endotoxemia was associated with significantly increased mortality risk for Neisseria meningitidis (4 studies; 138 bacteremias; OR 26.0; 95% CI, 1.6-321) but not for Salmonella enterica serovar Typhi (3 studies; 36 bacteremias; OR 0.89; 95% CI, 0.01-74.1). For 17 unrestricted studies (319 GN bacteremic patients), endotoxemia was associated with an increased mortality risk with non-Escherichia coli Enterobacteriaceae such as Klebsiella and Enterobacter species (97 bacteremias; OR 3.7; 95% CI, 1.3-10.3). By contrast, E. coli (144 bacteremias; OR 0.78; 95% CI, 0.36-1.7), and non-Enterobacteriaceae species such as Pseudomonas species (78 bacteremias; OR 1.7; 95% CI, 0.7-4.6) had no increased mortality risk. That endotoxemia detection is predictive of mortality among patients bacteremic with non-E. coli Enterobacteriaceae but not E. coli is surprising given the presumed commonality of the hexa-acyl lipid A structure among Enterobacteriaceae species.

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Endotoxemia and Bacteremia in Patients With Sepsis Syndrome in the Intensive Care Unit

Cited by 71 publications

References 34 publications

Toll-like Receptor Agonists and Febrile Range Hyperthermia Synergize to Induce Heat Shock Protein 70 Expression and Extracellular Release

Toll-like Receptor Agonists and Febrile Range Hyperthermia Synergize to Induce Heat Shock Protein 70 Expression and Extracellular Release

Diagnosis of Endotoxemia with Gram-Negative Bacteremia Is Bacterial Species Dependent: a Meta-Analysis of Clinical Studies

Prognostic Value of Endotoxemia in Patients with Gram-Negative Bacteremia Is Bacterial Species Dependent

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