Neonatal Nosocomial Infection Surveillance: Incidences by Site and a Cluster of Necrotizing Enterocolitis

Hentschel, Juliane; Veer, I. De; Gastmeier, Petra; Rüden, H.; Obladen, Michael

doi:10.1007/pl00012176

Cited by 29 publications

(15 citation statements)

References 23 publications

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“…We found a 41% increased risk of sepsis for SGA infants. VLBW infants were at increased risk for nosocomial infection, even after adjusting for length of NICU stay 33. The most important risk factors for nosocomial infection in this study were gestational age (adjusted ORs 1.35–2.01) and length of stay (adjusted ORs 2.03–5.74).…”

Section: Discussionmentioning

confidence: 53%

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Nosocomial infection in small for gestational age newborns with birth weight <1500 g: a multicentre analysis

Bartels

Schwab

Geffers

et al. 2007

Archives of Disease in Childhood - Fetal and Neonatal Edition

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Objective: To investigate whether preterm newborns who are small for gestational age are at increased risk of nosocomial infections and necrotising enterocolitis. Design, setting and subjects: The German national surveillance system for nosocomial infection in very low birthweight infants uses the US Centers for Disease Control and Prevention criteria. 2918 newborns (24-28 weeks), born between 2000 and 2004, were selected after application of predefined inclusion criteria to ensure similar proportions of small and appropriate weight for gestational age newborns across gestational age groups. Main outcome measures: The outcome criterion was at least one episode of nosocomial sepsis, pneumonia or necrotising enterocolitis. Adjusted odds ratios and corresponding 95% CIs were calculated based on general estimating equation models. Results: The study population consisted of 13% (n = 392) small and 87% (n = 2526) appropriate weight for gestational age infants. 33% (n = 950) of the infants experienced at least one episode of sepsis: 42% (n = 163) of small and 31% (n = 787) of appropriate weight for gestational age newborns (adjusted OR 1.41, 95% CI 1.05 to 1.89). Pneumonia was diagnosed in 6% (n = 171) of infants: 8.4% (n = 33) of small and 5.5% (n = 138) of appropriate weight for gestational age newborns (adjusted OR 1.57, 95% CI 1.19 to 5.57). Necrotising enterocolitis was documented in 5.2% (n = 152) of infants: 7.1% (n = 28) of small and 4.9% of (n = 124) appropriate weight for gestational age newborns (adjusted OR 1.20, 95% confidence interval 0.75 to 1.94). Conclusions: Growth-retarded preterm infants seem to be at increased risk of nosocomial infection, irrespective of the responsible pathogen. Future immunological research should elucidate potential causal associations.

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Section: Discussionmentioning

confidence: 53%

“…Sepsis and NEC are the most common infections in VLBW infants 33. Moreover, NEC is the most frequent surgical emergency 37.…”

Section: Discussionmentioning

confidence: 99%

Nosocomial infection in small for gestational age newborns with birth weight <1500 g: a multicentre analysis

Bartels

Schwab

Geffers

et al. 2007

Archives of Disease in Childhood - Fetal and Neonatal Edition

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“…Specifically, the onset of NEC occurs at a time when the intestinal lumen is colonized by Gram-negative flora (54,55), which usually occurs at ϳ8 -10 days after birth (56 -58). Additional evidence for a role for bacteria in the pathogenesis of NEC is found in the fact that NEC outbreaks occur in clusters within neonatal intensive care units in a pattern that is indicative of an infective etiology (59) and that NEC clinically responds to the administration of broad-spectrum antibiotic therapy (60,61). A specific role for Gram-negative bacterial LPS in the pathogenesis of NEC is supported by the results of studies performed in newborn rats and piglets in which the oral or i.v.…”

Section: Discussionmentioning

confidence: 99%

A Critical Role for TLR4 in the Pathogenesis of Necrotizing Enterocolitis by Modulating Intestinal Injury and Repair

Leaphart

Cavallo

Gribar

et al. 2007

The Journal of Immunology

426

507

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Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in preterm infants and is characterized by translocation of LPS across the inflamed intestine. We hypothesized that the LPS receptor (TLR4) plays a critical role in NEC development, and we sought to determine the mechanisms involved. We now demonstrate that NEC in mice and humans is associated with increased expression of TLR4 in the intestinal mucosa and that physiological stressors associated with NEC development, namely, exposure to LPS and hypoxia, sensitize the murine intestinal epithelium to LPS through up-regulation of TLR4. In support of a critical role for TLR4 in NEC development, TLR4-mutant C3H/HeJ mice were protected from the development of NEC compared with wild-type C3H/HeOUJ littermates. TLR4 activation in vitro led to increased enterocyte apoptosis and reduced enterocyte migration and proliferation, suggesting a role for TLR4 in intestinal repair. In support of this possibility, increased NEC severity in C3H/HeOUJ mice resulted from increased enterocyte apoptosis and reduced enterocyte restitution and proliferation after mucosal injury compared with mutant mice. TLR4 signaling also led to increased serine phosphorylation of intestinal focal adhesion kinase (FAK). Remarkably, TLR4 coimmunoprecipitated with FAK, and small interfering RNA-mediated FAK inhibition restored enterocyte migration after TLR4 activation, demonstrating that the FAK-TLR4 association regulates intestinal healing. These findings demonstrate a critical role for TLR4 in the development of NEC through effects on enterocyte injury and repair, identify a novel TLR4-FAK association in regulating enterocyte migration, and suggest TLR4/FAK as a therapeutic target in this disease.

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“…39). An altered bacterial colonization pattern (40), the protective role of probiotics (41)(42)(43), occasional clustering of NEC in neonatal intensive care units (44), the observation that NEC does not occur in a sterile environment in utero, and the absence of NEC-like pathology in an acute NEC model in germfree rats (8) suggest that bacteria play a role in NEC pathogenesis, but underlying defects in host-pathogen interactions that might lead to NEC are unknown. Our present report elucidates the importance of bacteria and TLR4 on intestinal inflammation and necrosis and shows that 1) exposure to bacteria contribute to NEC in the neonatal rat model, 2) TLR4 gene expression decreases in intestines of healthy, MF pups after birth to very low levels, but increases in villus epithelium in formula-fed/ asphyxia-stressed rats, 3) high TLR4 expression correlates with increased iNOS and Gro/CINC (i.e., the functional correlate to human IL-8) expression, 4) the site of increased TLR4 and iNOS expression is the intestinal epithelium, and 5) in a novel neonatal mouse model of NEC, TLR4 mutant mice (C3H/HeJ) have a decreased incidence of NEC compared with control animals (C3HeB/FeJ).…”

Section: Discussionmentioning

confidence: 99%

The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis

Jilling

Simon

Lü

et al. 2006

The Journal of Immunology

354

330

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Bacteria are thought to contribute to the pathogenesis of necrotizing enterocolitis (NEC), but it is unknown whether their interaction with the epithelium can participate in the initiation of mucosal injury or they can act only following translocation across a damaged intestinal barrier. Our aims were to determine whether bacteria and intestinal epithelial TLR4 play roles in a well-established neonatal rat model and a novel neonatal murine model of NEC. Neonatal rats, C57BL/6J, C3HeB/FeJ (TLR4 wild type), and C3H/HeJ (TLR4 mutant) mice were delivered by Cesarean section and were subjected to formula feeding and cold asphyxia stress or were delivered naturally and were mother-fed. NEC incidence was evaluated by histological scoring, and gene expression was quantified using quantitative real-time PCR from cDNA generated from intestinal total RNA or from RNA obtained by laser capture microdissection. Spontaneous feeding catheter colonization or supplementation of cultured bacterial isolates to formula increased the incidence of experimental NEC. During the first 72 h of life, i.e., the time frame of NEC development in this model, intestinal TLR4 mRNA gradually decreases in mother-fed but increases in formula feeding and cold asphyxia stress, correlating with induced inducible NO synthase. TLR4, inducible NO synthase, and inflammatory cytokine induction occurred in the intestinal epithelium but not in the submucosa. NEC incidence was diminished in C3H/HeJ mice, compared with C3HeB/FeJ mice. In summary, bacteria and TLR4 play significant roles in experimental NEC, likely via an interaction of intraluminal bacteria and aberrantly overexpressed TLR4 in enterocytes.

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Neonatal Nosocomial Infection Surveillance: Incidences by Site and a Cluster of Necrotizing Enterocolitis

Cited by 29 publications

References 23 publications

Nosocomial infection in small for gestational age newborns with birth weight <1500 g: a multicentre analysis

Nosocomial infection in small for gestational age newborns with birth weight <1500 g: a multicentre analysis

A Critical Role for TLR4 in the Pathogenesis of Necrotizing Enterocolitis by Modulating Intestinal Injury and Repair

The Roles of Bacteria and TLR4 in Rat and Murine Models of Necrotizing Enterocolitis

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