Milo Duane Hilty

Concordance of Bacterial Cultures with Endotoxin and Interleukin-6 in Necrotizing Enterocolitis

Concordance between gram-negative enteric andother toxin-producing bacteria in blood and stoolculture, endotoxin (lipopolysaccharide), andinterleukin-6 (IL-6) was measured in 60 preterm infants(600-1600 g) as a clinical index in neonatal necrotizingenterocolitis (NEC). E. coli, Klebsiella, Enterobacter,and Clostridium spp., identified by routinebacteriology, were each strongly associated withelevated concentrations of endotoxin (P < 0.01) instool filtrates, with Clostridium spp. most stronglyassociated with NEC disease. Stool filtrate endotoxin(EU/g) measured by a Limulus amebocyte lysate assay was age dependent. Samples from stage I NEC (61%)and infants with advanced disease (67%) had notablyelevated levels of stool endotoxin (>10 ln EU/g)compared to NEC-negative (47%) samples tested. Plasmaand stool IL-6 generally tested at the low,nonmeasurable limit of the ELISA for NEC-negative (88%)and stage I NEC (93%), although a small proportion ofsamples (25%) from infants with stage II or III NEC had elevated stool concentrations of IL-6. Weconclude that identification of toxin-producingorganisms and endotoxin elevations in stool filtratesare more useful than circulating levels of endotoxin in plasma in predicting mucosally limited diseasein the gastrointestinal tract. The prognostic value ofmonitoring stool endotoxin in infants with overgrowth ofgram-negative bacteria has implications for therapeutic strategies in patients with earlyand advanced stages of disease. Monitoring inflammatorycytokines (IL-6) in relation to endotoxin values instool appears of limited clinical value in controlling this devastating disease in pretermneonates.

FEEDING OF A PROBIOTIC FOR THE PREVENTION OF COMMUNITY-ACQUIRED DIARRHEA IN YOUNG MEXICAN CHILDREN. † 1089

FEEDING OF A PROBIOTIC FOR THE PREVENTION OF COMMUNITY-ACQUIRED DIARRHEA IN YOUNG MEXICAN CHILDREN. † 1089

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

Bacterial translocation and enteral feeding are factors implicated in neonatal necrotizing enterocolitis (NEC) in the preterm infant. A cohort of 60 preterm low birth‐weight (LBW) infants (600–1,600 g at birth) consecutively admitted to the neonatal intensive care unit (NICU; N = 183) were prospectively followed to evaluate the role of bacterial endotoxins (lipopolysaccharides) and enteral feeding in the development of NEC. Stage I NEC was identified in 14/60 (23%) infants. In all, 15% (9/60) of infants followed, which represented roughly 5% of higher risk, LBW infants admitted to the NICU, progressed to Stage II or III NEC disease. Infants not enterally fed (nothing by mouth [NPO]) were at greatest risk of developing NEC. No infant who was breast milk fed progressed to Stage II or III NEC. The protective effect of breast milk was most evident when compared with the combined group of NPO or formula‐feeding infants per person‐week at risk (RR = .15, P < .04). Toxin‐producing bacteria and endotoxin levels in stool filtrates predicted early and advanced stages of NEC disease. Cytokine concentrations (interleukin‐6 [IL‐6]) in stool appeared of limited value in reflecting mucosally limited disease in the gastrointestinal tract. Overgrowth of toxin‐producing bacteria and their toxin products may adversely affect gut barrier function; monitoring endotoxin concentrations in stool filtrates may be most clinically useful in NPO and formula‐fed infants identified at risk of developing NEC. Am. J. Hum. Biol. 10:211–219, 1998.

BACTERIAL TOXINS AND ENTERAL FEEDING OF PREMATURE INFANTS AT RISK FOR NECROTIZING ENTEROCOLITIS. † 1559

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.