PMID: 6398946Jan 1, 1984Paper

Endotoxemia induced by antibiotic therapy: a mechanism for adrenal corticosteroid protection in gram-negative sepsis

Transactions of the Association of American Physicians
C A Johnston, S E Greisman

Abstract

The following have been demonstrated: With a standardized model of P. mirabilis peritonitis in ICR mice, when optimal doses of an aminoglycoside antibiotic (kanamycin) are given so as to reduce mortality maximally, abrupt and significant increments occur in endotoxemia, which cannot be attributed to impairment of clearance of endotoxin. Within the antibiotic-treated groups, these increments in endotoxemia correlate with mortality. The level of endotoxemia in the antibiotic-treated survivors is significantly greater than in animals dying without antibiotic therapy. MP, although unable to reduce mortality from P. mirabilis peritonitis in the absence of antibiotic therapy, does so when endotoxin is added to the challenge inoculum. It is concluded from these observations that aminoglycoside antibiotic treatment can shift the lethal mechanisms during P. mirabilis peritonitis from those involving bacterial proliferation and low levels of endotoxemia to those involving bacterial death and release of large amounts of endotoxin. It is postulated that this shift in lethal mechanisms could account for the ability of MP to reduce mortality when used in conjunction with antibiotics. Finally, since animals surviving after antibiotic treatmen...Continue Reading

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