Abstract 1141 Poster Session IV, Tuesday, 5/4 (poster 237)

Abnormal bacterial flora on the skin, and within the respiratory and intestinal tracts, are the main reservoirs for infections acquired by hospitalized newborn infants. Reports suggest that newborn infants are protected from infection by human milk because it helps establish a non-invasive bacterial flora in the intestines. Premature infants often receive cow milk-based formulas rather than human milk placing them at risk for gut-associated infections. The availability of recombinant lactoferrin (rh-LF) allowed us to study whether rh-LF, given by gastric gavage to 4 day old newborn rats, would decrease bacteremia and prevent illness or death after gut infection with Escherichia coli (an infective dose of 1012 colony forming units (CFUs)/kg of body weight). Two doses of rh-LF were given 24 hours before E. coli infection. Forty-eight hours after infection, surviving newborn rats were studied by obtaining quantitative blood and liver cultures. In the control pups receiving oral NaCl (n = 15), all blood cultures were positive (6.7 × 107 ± 4.4 × 107 CFUs/ml), while the rh-LF group (n = 22) had 20 positive blood cultures (7.0 × 104 ± 3.3 × 104 CFUs/ml, mean SEM, P <0.001 v. NaCl). Dying animals had blood cultures that, on average, contained 4.5 × 108 CFU/ml of blood. Aseptic liver touch cultures in the NaCl group were 241 ± 31 CFU, while the rh-LF liver cultures were 114 ± 33 CFU (P <0.01). A clinical scoring system was developed to ascertain the level of illness from infection. Clinical scores of animals in the NaCl and rh-LF groups are shown below: (Table) The differences in no illness and death or dying between the two groups were highly significant (P<0.001). When 5 mg/kg of FeSO4 was given by gavage along with NaCl or rh-LF, bacteriologic results and clinical status were similar to those without iron. The blood cultures obtained in the NaCl group (n = 10) were 2.3 × 107 ± 8.1 × 106 CFU/ml(mean SEM), while the rh-LF group (n = 9) were 2.8 × 105 ± 2.7 × 105 CFU/ml (P<0.05 v. NaCl treated pups). The liver cultures obtained in the NaCl group were 236 ± 41 CFU, while the rh-LF groups cultures were 75 ± 35 CFU (P<0.02). These results suggest that rh-LF does not limit the growth of E. coli by iron restriction. An alternative mechanism of action is that the lactoferricin domain in the N-lobe of rh-LF either exerts an antibacterial effect on E. coli or it binds endotoxin thereby limiting the pro-inflammatory effects of lipopolysaccharide. Regardless of the mechanism, we conclude that, in this newborn rat model, rh-LF treatment reduces bacterial infection, illness and death after massive gut infection with Escherichia coli.

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The research was funded by Ross Laboratories.