Bacterial toxins and enteral feeding of premature infants at risk for necrotizing enterocolitis

Concordance between gram-negative enteric and other toxin-producing bacteria in blood and stool culture, endotoxin (lipopolysaccharide), and interleukin 6 (IL-6) was measured in 60 preterm infants (600-1600 g) as a clinical index in neonatal necrotizing enterocolitis (NEC). Escherichia coli, Klebsiella, Enterobacter, and Clostridium spp, identified by routine bacteriology, were each strongly associated with elevated concentrations of endotoxin (P < 0.01) in stool filtrates with Clostridium spp most strongly associated with NEC disease. Stool filtrate endotoxin (endotoxin units [EU] per gram) measured by a Limulus amebocyte lysate assay was age-dependent. Samples from stage I NEC (61%) and infants with advanced disease (67%) had notably elevated levels of stool endotoxin (>10 ln EU/g) compared with NEC-negative (47%) samples tested. Plasma and stool IL-6 generally tested at the low, nonmeasurable limit of the enzyme-linked immunosorbent assay (ELISA) for NEC-negative (88%) and stage I NEC (93%), although a small proportion of samples (25%) from infants with stage II or II NEC had elevated stool concentrations of IL-6. We conclude that identification of toxin-producing organisms and endotoxin elevations in stool filtrates are more useful than circulating levels of endotoxin in plasma in predicting mucosally limited disease in the gastrointestinal tract. The prognostic value of monitoring stool endotoxin in infants with overgrowth of gram-negative bacteria has implications for therapeutic strategies for patients with early and advanced stages of disease. Monitoring inflammatory cytokines (IL-6) in relation to endotoxin values in stool appears of limited clinical value in controlling this devastating disease in preterm neonates.