Bactericidal antibiotics increase tumor necrosis factor-alpha and cardiac output in rats after cecal ligation and puncture.
We hypothesized that treatment of experimental sepsis with bactericidal antibiotics, known to enhance microbial toxin release, would alter tumor necrosis factor-alpha production and the hemodynamic response to the syndrome. In the rat, after cecal ligation and puncture (CLP), elevated serum TNF levels and cardiac output were observed following antibiotic treatment. TNF and cardiac output were elevated to a greater extent in bactericidal-treated than bacteriostatic-treated or antibiotic-untreated rats. Animals treated with bactericidal antibiotics also had significantly greater cardiac outputs than untreated rats. Despite increases in circulating TNF with antibiotic administration, the mortality rate at 96 hr decreased after either bactericidal or bacteriostatic antibiotics. We conclude that elevated TNF after CLP in rats treated with antibiotics is associated with enhanced hemodynamic responses to CLP, but does not increase early mortality. In this model of polymicrobial sepsis, bactericidal and bacteriostatic antibiotics led to different hemodynamic effects without compromising survival.
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
J A
JA
Stockwell
Y C
YC
Huang
Y F
YF
Su
C A
CA
Piantadosi
D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects*; D002432:Cecum / Q000601:surgery*; D002701:Chloramphenicol / Q000494:pharmacology; D004731:Endotoxins / Q000097:blood; D005839:Gentamicins / Q000494:pharmacology; D006439:Hemodynamics; D007700:Kinetics; D008026:Ligation; D008168:Lung / Q000033:anatomy & histology; D009929:Organ Size; D011677:Punctures; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D005839:Gentamicins; D014409:Tumor Necrosis Factor-alpha; D002701:Chloramphenicol; D000667:Ampicillin