Prevention of the generalized Shwartzman reaction and endotoxin lethality by polymyxin B localized in tissues.

Abstract:

:Pretreatment with multiple doses of polymyxin B and colistimethate was evaluated as to its ability to sequester sufficient antibiotic in tissues to neutralize the effects of endotoxin in three animal models. Animals were challenged with endotoxin 24, 48, or 72 h after the last dose of antibiotic when there was minimal or not detectable drug in serum. Pretreatment with polymyxin B was successful in preventing the generalized Shwartzman reaction in rabbits and reducing endotoxin lethality in mice; however, large doses (20 mg per kg per day for 2 or 4 days) were required. Prolongation by more than 24 h of the interval between the last dose of polymyxin B and endotoxin challenge resulted in reduction or loss of protection. Dogs were unable to tolerate the high polymyxin B dosage which was protective in the mouse and rabbit. Lower, nontoxic doses of polymyxin B in dogs did not prevent endotoxin shock and lethality, even when challenged as soon as 1 h after the last dose. Pretreatment with colistimethate was ineffective in all three animal models.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Craig WA,Turner JH,Kunin CM

doi

10.1128/IAI.10.2.287-292.1974

subject

Has Abstract

pub_date

1974-08-01 00:00:00

pages

287-92

issue

2

eissn

0019-9567

issn

1098-5522

journal_volume

10

pub_type

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