Effectiveness of Steroid/Antibiotic Treatment in Primates Administered LD100 Escherichia coli

Hinshaw, Lerner B.; Beller-Todd, B K; Archer, L. T.; Benjamin, Bruce; Flournoy, D. J.; Passey, Richard B.; Wilson, Michael F.

doi:10.1097/00000658-198107000-00009

Cited by 56 publications

(19 citation statements)

References 6 publications

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“…These studies clearly documented the outstanding effectiveness of the combined treatment regimen of ste-25 roid and antibiotics in several species of animals subjected to lethal septic shock. 24,[28][29][30][31][32][33][34][35][36][37][38][39][40][41] These findings add support to the results of the human clinical study reported by Schumer ( Table 5).…”

Section: Animal Studiessupporting

confidence: 80%

Corticosteroids in Shock

Hinshaw¹

1985

Semin Respir Crit Care Med

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Section: Animal Studiessupporting

confidence: 80%

Corticosteroids in Shock

Hinshaw¹

1985

Semin Respir Crit Care Med

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“…Antibiotic treatment concomitant with dexamethasone treatment is more effective than dexamethasone treatment alone for treatment of shock resulting from exposure to live bacteria (Pitcairn et al 1975, Hinshaw et al 1981. For example, antibiotics in combination with dexamethasone protect against S. aureus whereas dexamethasone alone was ineffective (Silverstein et al 2000, Silverstein & Johnson 2003.…”

Section: Live Bacteriamentioning

confidence: 99%

Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products

Webster

Sternberg

2004

Journal of Endocrinology

164

124

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The hypothalamic-pituitary-adrenal (HPA) axis is activated during many bacterial and viral infections, resulting in an increase in circulating glucocorticoid levels. This HPA axis activation and glucocorticoid response are critical for the survival of the host, as demonstrated by the fact that removal of the HPA axis (by adrenalectomy or hypophysectomy) or glucocorticoid receptor (GR) blockade enhances the severity of the infection and in some cases enhances the mortality rate. Replacement with a synthetic glucocorticoid reverses these effects by reducing the severity of the infection and provides protection against lethal effects. In addition, some bacteria and viral infections have been shown to affect the GR directly. These have been described and the implications of such an effect discussed.

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“…But, baboons and other monkey species tend to be remarkably resistant to the lethal effects of intravenously administered LPS or viable bacteria. Thus, in the classic Hinshaw model of lethal sepsis in baboons, the animals are infused with more than 10 10 colony forming units (cfu)/kg of viable E. coli bacteria 65 . Blood cultures in this model contain 10 3 to 10 7 cfu/ml, i.e., levels of bacteria that are much greater than are commonly observed in lethal human septic shock.…”

mentioning

confidence: 99%

Animal models of sepsis

Fink¹

2013

Virulence

324

284

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Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism.

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Effectiveness of Steroid/Antibiotic Treatment in Primates Administered LD100 Escherichia coli

Cited by 56 publications

References 6 publications

Corticosteroids in Shock

Corticosteroids in Shock

Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products

Animal models of sepsis

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