Enhanced toxicity for mice of combinations of antibiotics with Escherichia coli cells or Salmonella typhosa endotoxin.
Enhanced lethality for BALB/c mice has been observed after the administration of Salmonella typhosa endotoxin with either actinomycin D, cycloheximide, or nogalamycin. The dose of actinomycin D required to kill half of the mice (LD(50)) was 0.8 mg/kg in normal animals, 0.35 mg/kg in mice administered 0.08 mg of endotoxin per kg, and 0.28 mg/kg in mice administered 0.2 mg of endotoxin per kg. The LD(50) of endotoxin in normal mice was 12 mg/kg and in mice given 0.4 mg of actinomycin D per kg was 0.067 mg/kg. The LD(50) of actinomycin D in mice administered 1.8 x 10(8) live Escherichia coli cells per kg or 1.8 x 10(9) heat-killed E. coli cells per kg was reduced to 0.4 mg/kg. The LD(50) of cycloheximide was 181 mg/kg in normal animals and 28 mg/kg in mice administered 4 mg of endotoxin per kg. The LD(50) of endotoxin in mice given 120 mg of cycloheximide per kg was 0.02 mg/kg. Enhanced lethality due to various combinations of cycloheximide and endotoxin was abolished by pretreatment of mice with endotoxin. The LD(50) of nogalamycin was 21 mg/kg in normal mice and 13 mg/kg in mice receiving 1 mg of endotoxin per kg.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D003513:Cycloheximide / Q000633:toxicity; D003609:Dactinomycin / Q000633:toxicity; D004357:Drug Synergism; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D006358:Hot Temperature; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D012485:Salmonella typhi; D013997:Time Factors
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D003609:Dactinomycin; D003513:Cycloheximide