Endotoxin filtration and immune stimulation improve survival from gram-negative sepsis.
Polymyxin B, when bound to a polystyrene fiber (PMX-F), has been used experimentally as an extracorporeal blood filter to reduce serum lipopolysaccharide levels, which are believed to be responsible for physiologic alterations in the septic state. To validate our theory that a combination of PMX-F, systemic antibiotics, and immune stimulation would improve survival, 78 rats were given intravenous doses of Escherichia coli (range, 4.6 to 6.2 X 10(8) colony-forming units/ml). They were then randomized into groups receiving either systemic gentamicin (n = 10); pretreatment with muramyl dipeptide (n = 11); or extracorporeal hemoperfusion through either a sham column (n = 8), PMX-F-packed column with systemic gentamicin (n = 8); or PMX-F-packed column with systemic gentamicin and muramyl dipeptide pretreatment (n = 8). Thirty-three control rats received no treatment. Sham hemoperfusion (13%) and control (21%) rats had the lowest survival rate, although increased improvement was noted in rats treated with gentamicin (30%) or the combination of PMX-F filtration and gentamicin (50%). The most significant improvements occurred in rats pretreated with muramyl dipeptide (53%) and in rats treated with a combination of PMX-F, gentamicin, and muramyl dipeptide (88%). These data show that lipopolysaccharide filtration and nonspecific immune stimulation are additive to antibiotic therapy and are useful as adjunctive measures in the multimodal treatment of experimental gram-negative bacterial infection.
Cheadle
W G
WG
Department of Surgery, University of Louisville, KY 40292.
Hanasawa
K
K
Gallinaro
R N
RN
Nimmanwudipong
T
T
Kodama
M
M
Polk
H C
HC
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000627:therapeutic use; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000991:Antithrombins / Q000627:therapeutic use; D001550:Benzamidines; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D005839:Gentamicins / Q000627:therapeutic use; D016905:Gram-Negative Bacterial Infections / Q000401:mortality / Q000628:therapy*; D006146:Guanidines / Q000627:therapeutic use; D006440:Hemofiltration / Q000379:methods*; D008297:Male; D011112:Polymyxin B / Q000008:administration & dosage / Q000627:therapeutic use; D011137:Polystyrenes; D051381:Rats; D011919:Rats, Inbred Strains; D016019:Survival Analysis
D000276:Adjuvants, Immunologic; D000991:Antithrombins; D001550:Benzamidines; D004731:Endotoxins; D005839:Gentamicins; D006146:Guanidines; D011137:Polystyrenes; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D011112:Polymyxin B; C032855:nafamostat