Lipid X, the major
monosaccharide precursor of
lipid A, is nontoxic and has previously been shown to protect mice and sheep from the harmful effects of
endotoxin. To test the hypothesis that
lipid X could be therapeutic against
infections with gram-negative organisms, neutropenic ICR mice were infected by intramuscular inoculation of Escherichia coli and subsequently treated with
lipid X alone or in combination with the
antibiotic ticarcillin.
Lipid X slightly prolonged survival; treated mice had a significantly improved rate of survival 18 h after intramuscular inoculation as compared with controls (P less than 0.025). By 24 h, however, this difference disappeared. When
lipid X was combined with
ticarcillin, survival differences were both significant and prolonged. Treatment of mice with one to two doses of
lipid X for a total dose of 1 mg intravenously and with 1,200 mg of
ticarcillin per kg every 6 h improved survival over a 48-h treatment period from 5 to 23% (P less than 0.0025). Treatment with
lipid X and
ticarcillin over a broad range of
antibiotic dosages in 362 mice demonstrated improved survival of two- to fourfold (P less than 0.0001 at 24 h after inoculation, P less than or equal to 0.0005 at 48 h, and P less than or equal to 0.0001 at 5 days).
Lipid X enabled the dose of
ticarcillin necessary to protect 50% of mice from death to be reduced by two- to fivefold. Pretreatment with
lipid X was not necessary to improve survival: 16 of 17 (94%) infected and visibly ill animals that received
lipid X and
ticarcillin 6 h after thigh inoculation survived versus 30 of 44 (68%) control animals treated with
ticarcillin alone (P less than 0.0001).
Lipid X had no antimicrobial activity in vitro.
Lipid X is a novel agent that enhances survival in an animal model of severe
infection with gram-negative organisms.