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Nosocomial necrotising enterocolitis outbreaks: epidemiology and control measures.

UNLABELLED: Necrotising enterocolitis (NEC) is one of the most serious gastrointestinal diseases among newborns and it mainly affects those in intensive care units. The aetiology of the disease has been reported to be multifactorial and both sporadic cases and nosocomial outbreaks have occurred. In this report, we review 17 epidemics of NEC reported in the literature between 1973 and 1999. The number of confirmed cases ranged from 1 to 32 with an average of 10.5 confirmed cases. On average, 16.15% of cases required surgery (range 0-66.6%). The average mortality rate was 6.25% (range 0-87.5%). The mean age at disease onset was 9.5 days (range 6.6-29 days). Most of the infants had low birth weight (median weight 1,395 g; range 1,112-2,788 g, calculated on the reported mean weights). The main risk factors associated with NEC were: low birth weight, low gestational age, low Apgar score, perinatal complications, hyaline membrane disease, and umbilical catheterisation. The bacteria involved often included Enterobacteriaceae, particularly Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae type 3305573. The causative role of Clostridia in NEC is controversial. With regard to viral agents, coronarovirus, rotavirus and enterovirus, such as echovirus type 22, were isolated during some of the epidemics. The recommended control measures for NEC epidemics are those used for epidemics of other orofaecally transmitted infections. CONCLUSION: Understanding the epidemiology of necrotising enterocolitis is fundamental if adequate preventive control measures are to be developed and applied.

Cross Infection↗

Detection of Candida mannoproteinemia in patients with neutropenic enterocolitis.

To assess the role of Candida spp. in the etiology of neutropenic enterocolitis complicating aggressive cytotoxic chemotherapy, a dot immunobinding assay for an immunodominant Candida mannoprotein antigen was employed in 20 patients with hematologic malignancies. Candida antigen was detected in at least one serum sample from 12 (60%) patients. Eleven (92%) patients were cured when an antifungal agent was added to the antibacterial treatment. In eight patients a selective anticandidal therapy with fluconazole was administered on the basis of positive Candida mannoproteinemia, and treatment was successful in all cases but one. Detection of Candida mannoproteinemia seems to be a useful diagnostic tool in patients with neutropenic enterocolitis and represents an additional tool for selecting a less empiric, low toxic antifungal treatment with fluconazole.

Adolescent↗

Enterocolitis associated with cocaine use.

PURPOSE: Cocaine use has been reported to cause gastrointestinal complications. This retrospective review describes the presentation and clinical course of cocaine-associated enterocolitis. METHODS: Charts with a diagnoses of colitis or abdominal pain, between 1991 to 2001, were reviewed for a positive urine drug screen or documented cocaine use. Data about the patients' symptoms and physical findings, results of clinical studies, and outcome were collected. RESULTS: There were 18 patients identified. The interval from last use to the onset of pain was fewer than one day for seven patients, one to three days for seven patients, and more than three days for four patients. Physical examination demonstrated diffuse peritonitis in 2 patients, tenderness localized to a single quadrant in 11 patients, and tenderness in two or more quadrants in 5 patients. Computed tomography was obtained in 11 patients with 10 demonstrating signs of inflammation or ischemia. The anatomic locations of disease were proximal colon (14 patients), small bowel/gastric (1 patient), and distal colon (3 patients). The initial management was nonoperative in 15 patients. One patient presented in shock and died. Another developed peritonitis and underwent laparotomy. Surgical intervention occurred in four patients (3 initially, 1 on Day 4) for peritonitis. Two died postoperatively, a 50-percent surgical mortality. CONCLUSIONS: Cocaine-associated enterocolitis usually presents within three days of cocaine use. Inflammatory or ischemic changes are most common in the proximal colon. The majority of patients will recover with nonoperative therapy; however, those who develop peritonitis and undergo laparotomy have a 50 percent mortality.

Adult↗

Association with selected bacteria does not cause enterocolitis in IL-10 gene-deficient mice despite a systemic immune response.

Resident bacteria have been implicated to play a major role in the development of inflammatory bowel disease. While luminally sterile IL-10 gene-deficient mice remain disease-free, their conventionally raised littermates develop enterocolitis associated with increased numbers of luminal and mucosal adherent bacteria. To investigate the role of defined bacteria on the initiation and development of this enterocolitis, we associated luminally sterile IL-10 gene-deficient mice with pure strains of resident bacteria. Axenic, luminally sterile mice were either monoassociated with viridans group Streptococcus or Clostridium sordellii or co-associated with Bacteroides vulgatus and Clostridium sordellii. Seven to 22 weeks later the mice were analyzed for intestinal histologic injury, epithelial permeability, and an inflammatory immune response to bacterial antigens. Despite optimal colonization none of the tested bacteria caused intestinal inflammation, release of inflammatory cytokines from the epithelia, or disruption of the epithelial barrier integrity. However, in the case of association with Bacteroides vulgatus and Clostridium sordellii, a systemic immune response to bacterial-derived antigens was measured, with a magnitude similar to that seen in conventional sick Il-10 gene-deficient mice. This response was not detected in mice associated with viridans group Streptococcus. We conclude that colonization of the intestinal lumen with individual bacterial species may not be sufficient to alter epithelial barrier integrity, increase intestinal cytokine release, or cause intestinal inflammation in susceptible IL-10 gene-deficient mice, despite the ability of these same bacteria to stimulate a systemic response.

Animals↗

Intestinal stenosis resulting from necrotizing enterocolitis.

Fourteen infants with intestinal stenosis as a late sequela of necrotizing enterocolitis were treated at Texas Children's and Ben Taub General Hospitals from 1972 to 1979. Barium enema studies are the keystone in making the diagnosis and should be performed in any infant with abdominal distention or poor feeding after recovery from acute necrotizing enterocolitis. Spontaneous resolution of stenosis is a definite clinical entity, and nonobstructed infants should be given a trial for resolution. This trial should be for a limited time. The operative therapy for the infant with obstruction or the infant who fails to have spontaneous resolution of stenosis must be individualized. Resection with primary anastomosis best serves those infants with limited stenotic lesions, minimal dilatation of the intestinal lumen and no other complicating medical problems. Intestinal diversion with later resection and enterostomy closure should be reserved for infants with intestinal obstruction and complicating medical problems.

Adolescent↗

An animal model of necrotizing enterocolitis induced by infant formula and ischemia in developing piglets.

BACKGROUND/AIMS: The lipid component of piglet formula (0.5% fat) causes increased mucosal permeability in 1-day-old piglets after ischemia/reperfusion. The present study examined if luminal exposure to infant formulas (3.5% fat) and ischemia/reperfusion result in an animal model of necrotizing enterocolitis and if injury is dependent on the formula fat composition. METHODS: Plasma-to-lumen clearance of 51Cr-ethylenediamine-tetraacetic acid was measured, and morphology was evaluated during luminal perfusion with preterm, term, and delipidated preterm cow milk-based infant formulas before and after ischemia/reperfusion in 1-day-old and 1-month-old piglet jejunoileum. In a separate set of experiments, a 1-2-cm segment of ileum was exteriorized and opened to expose the mucosal surface, and the villi were superfused with the above formulas (no ischemia). RESULTS: Before ischemia, clearances were markedly higher for intestinal loops perfused with preterm formula than for loops perfused with term and delipidated formulas in 1-day-old animals. After ischemia, clearances in loops perfused with preterm formula were significantly greater and grossly hemorrhagic and histologically necrotic compared with loops perfused with delipidated formula (minimal injury). Superfusion with preterm formula caused diffuse hyperemia and hemorrhage into intestinal villi. CONCLUSIONS: Luminal perfusion of 1-day-old piglet jejunoileum with predigested and bile acid-solubilized preterm infant formula, in combination with ischemia/reperfusion, produces an animal model of necrotizing enterocolitis, but only if the lipid fraction of the formula is present.

Animal Feed↗

T-cryptantigen exposure in neonatal necrotizing enterocolitis.

Sixty-two infants with necrotizing enterocolitis were prospectively evaluated for evidence of the Thomson-Friedenreich cryptantigen (TCA) on their red cell surfaces. The TCA is exposed when bacterially derived neuraminidase acts on the surface of the red cells, cleaving off the N-acetylneuraminic acid, which hides the antigen. Seventeen patients (27%) had red cell TCA exposure as demonstrated by agglutination of their red cells by peanut lectin. This test is a simple agglutination procedure, which can be easily performed and yields results in a matter of minutes. Patients with TCA exposure require surgery 76% of the time compared with 18% of the time of those who did not demonstrate this phenomenon, a highly significant difference (P less than .01). All patients strongly positive for TCA exposure had intestinal perforations found at laparotomy. Patients with TCA exposure had clostridia cultured from blood, peritoneal fluid, or stool in 88% of the cases. Isolation of Clostridium perfringens was highly associated with strong TCA exposure and advanced disease. Since naturally occurring anti-TCA is found in normal adult plasma, hemolysis was observed in TCA-exposed patients who received plasma-containing blood products. The presence of TCA exposure in babies with necrotizing enterocolitis had prognostic and therapeutic implications. It indicates the need for antibiotic coverage against anaerobic organisms, strict avoidance of plasma-containing blood products, and the use of washed blood products if the patient is to be transfused. It also alerts the surgeon to the possibility of early operative intervention.

Agglutination Tests↗

Indium 111 oxine-labeled leukocytes for early diagnosis of ischemic enterocolitis.

The feasibility of the use of indium 111 oxine-labeled autologous leukocytes for the diagnosis of ischemic enterocolitis in vivo was examined in an experimental model of ischemia in dogs. A 30-cm segment of small intestine was devascularized by ligating the arteries and veins from the last arcade in 7 dogs. A sham operation was performed in 3 control dogs. 111In oxine-labeled autologous white blood cells were infused 3.5 hours after operation. Anterior and lateral nuclear scanning was performed at 6 and 24 hours postinfusion with a gamma camera equipped with a low-energy magnifying multihole collimator. The animals were killed after 24 hours. The gross and microscopic appearance of the bowel was evaluated. The radioactivity in the serial specimens of the bowel was measured. In vivo scans were positive (ie, increased uptake in the bowel loop) in all dogs with intestinal ischemia at 6 and 24 hours. No significant uptake was noted in control dogs. Rectilinear scan of the bowel removed at autopsy showed a correlation between the area of infarction and tracer accumulation. In addition, there was a progressive decrease in uptake of 111In oxine from the center of the ischemic lesions to the periphery. Forty percent of the total radioactivity was measured at the center of the lesion, whereas only 6.5% was present at 22.5 cm from the center. Thus the ratio between the ischemic and normal tissue was 10:1 (range, 6.5 to 16). These studies demonstrate that 111In oxine-labeled autologous white blood cells can be used for the diagnosis of ischemic enterocolitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Colonic hyperganglionosis presenting as neonatal enterocolitis and multiple strictures.

Neuronal intestinal dysplasia (NID) usually mimics Hirschsprung's disease, but rarely presents as neonatal enterocolitis. The authors report a case of colonic hyperganglionosis, which is a form of NID, presenting with postenterocolitis intestinal strictures. NID should be considered as a possible (although rare) cause of neonatal enterocolitis and may present with intestinal strictures.

Colon↗

Enterocolitis associated with Hirschsprung's disease: a clinical-radiological characterization based on 168 patients.

The enterocolitis associated with Hirschsprung's disease (HD) has not been clearly characterized. This study was undertaken to analyze the clinical and radiological findings of Hirschsprung's enterocolitis (HEC) in 168 patients treated from July 1974 through October 1992. HEC occurred in 57 patients (33.9%), either preoperatively (13; 7.7%) or postoperatively (36; 21.4%). In eight patients (4.8%), it occurred pre- and postoperatively. The number of bouts of HEC per patient ranged from one to six (mean, 2.2). The major presenting features were abdominal distension (83%), explosive diarrhea (69%), vomiting (51%), fever (34%), lethargy (27%), rectal bleeding (5%), and colonic perforation (2.5%). There were no deaths directly related to HEC. The analysis of 150 plain x-rays of the abdomen, taken at the onset of HEC or in between bouts, showed that colonic dilatation was the most sensitive radiological finding (90% sensitivity), but it had poor specificity (24%). However, an intestinal cutoff sign (gaseous intestinal distension with abrupt cutoff at the level of the pelvic brim) was both sensitive (74%) and specific (86%) for HEC. Barium enema was of limited value in the diagnosis of HEC bouts because most of the radiographic findings persisted for prolonged periods after cessation of such bouts. The authors conclude that (1) HEC can be characterized as abdominal distension and explosive diarrhea associated with the intestinal cutoff sign and (2) the occurrence of explosive diarrhea in any patient with HD is suggestive of HEC, even in the absence of systemic symptoms, and should be treated to avoid the morbidity and potential mortality of HEC.

Barium Sulfate↗

[Necrotizing enterocolitis during pregnancy in a woman operated on at six months of Hirschsprung's disease].

Necrotizing enterocolitis is a rare and severe complication of Hischsprung's disease. Aggravation of unknown or undertreated Hischsprung's disease may be seen during pregnancy. To our knowledge, the following case is the first combining those two elements: necrotizing enterocolitis in a 20 years old women operated on of Hischsprung's disease when she was six months. The final diagnosis was made 24 hours later. Definitive treatment was a three-stage ileal pouch-anal anastomosis.

Adult↗

Prevalence of pigs infected by Salmonella Typhimurium at slaughter after an enterocolitis outbreak.

A cross-sectional study was performed to estimate the prevalence of slaughter pigs infected by Salmonella typhimurium after an enterocolitis outbreak in a commercial pig farm, which was characterised by diarrhoea during the growing phase. Anatomopathological and histopathological findings were suggestive of salmonellosis, which was further confirmed by isolation of S. typhimurium from organs and faeces samples from diseased animals. Ileocolic lymph nodes were aseptically collected from 43 pigs during slaughter procedures. The estimated prevalence of Salmonella-infected pigs was 53.48% [confidence interval (CI): 42.94:64.02%]. This finding demonstrates that the carriage of S. typhimurium at slaughter might be high if pigs originate from a batch previously affected by Salmonella-enterocolitis outbreak at the pre-harvest pork production chain.

Abattoirs↗

Food protein-induced enterocolitis syndrome: case presentations and management lessons.

Enterocolitis induced in infants by cow's milk and/or soy protein has been recognized for decades. Symptoms typically begin in the first month of life in association with failure to thrive and may progress to acidemia and shock. Symptoms resolve after the causal protein is removed from the diet but recur with a characteristic symptom pattern on re-exposure. Approximately 2 hours after reintroduction of the protein, vomiting ensues, followed by an elevation of the peripheral blood polymorphonuclear leukocyte count, diarrhea, and possibly lethargy and hypotension. The disorder is generally not associated with detectable food-specific IgE antibody. There are increasing reports of additional causal foods, prolonged clinical courses, and onset outside of early infancy, leading to description of a food protein-induced enterocolitis syndrome. The disorder poses numerous diagnostic and therapeutic challenges. The purpose of this report is to delineate the characteristic clinical features and review the possible pathophysiologic basis to frame a rational strategy toward management.

Allergens↗

Nucleated red blood cells in preterm infants who have necrotizing enterocolitis.

Absolute nucleated red blood cell counts for 23 preterm newborn infants who subsequently had development of necrotizing enterocolitis were significantly higher than for 23 control infants. These infants may have been exposed to relative intrauterine hypoxemia, a possible risk factor for the development of necrotizing enterocolitis.

Case-Control Studies↗

Spontaneous liver hemorrhage during laparotomy for necrotizing enterocolitis: a potential role for recombinant factor VIIa.

Necrotizing enterocolitis remains a serious condition in very low birth weight infants, particularly in those infants who require surgery. Perioperative hemorrhage is a potentially fatal complication in this population. We describe our experience in 4 premature infants with necrotizing enterocolitis who received recombinant factor VIIa to manage life-threatening intraoperative hemorrhage.

Enterocolitis, Necrotizing↗

Experience of long-term synbiotic therapy in seven short bowel patients with refractory enterocolitis.

BACKGROUND/PURPOSE: Probiotic and prebiotic therapies are potent new strategies to treat various intestinal diseases, including inflammatory bowel disease and viral and bacterial infections. Synbiotics is defined as the combined use of probiotics and prebiotics and is expected to have a stronger effect on intestinal diseases than probiotics or prebiotics alone, but there has been no report of its clinical application. The authors designed a protocol for synbiotic therapy composed of Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides and preliminarily ascertained its clinical effects in humans. METHODS: This protocol of synbiotic therapy was applied for more than 1 year to 7 malnourished patients with short bowels who suffered from refractory enterocolitis. RESULTS: The therapeutic protocol improved the intestinal bacterial flora (inducing the domination by anaerobic bacteria and suppressing the residence of pathogenic bacteria) and increased short chain fatty acids in the feces (from 27.8 to 65.09 micromol/g wet feces). All patients but 1 accelerated their body weight gain, and 5 patients showed increased serum rapid turnover proteins. CONCLUSIONS: This protocol for synbiotic therapy might be a potent modulator of intestinal flora and a promising strategy to treat short bowel patients with refractory enterocolitis.

Adolescent↗

Protective effect of tumor necrosis factor alpha antibody on experimental necrotizing enterocolitis in the rat.

BACKGROUND: Necrotizing enterocolitis (NEC) is a common and devastating disorder of premature infants. Elevated proinflammatory cytokines, especially tumor necrosis factor alpha (TNF-alpha), have been implicated in the pathogenesis of NEC. The aim of this study was to evaluate the effects of TNF-alpha on the inflammatory response in NEC by immunoneutralizing TNF-alpha with a selective antibody. METHODS: Neonatal Sprague-Dawley rats were divided in 3 groups: group 1 (n = 20), a NEC-like enterocolitis was induced by formula feeding, asphyxia, and cold exposure; group 2 (n = 9), animals were treated like in group 1 and additionally received TNF-alpha antibody intraperitoneally; and group 3 (n = 17), animals were dam-fed (controls). Animals were killed in case of imminent death or after 96 hours. Specimens from small bowel were processed for blinded histologic (H&E) and immunhistologic (myeloperoxidase [MPO]) analysis. RESULTS: In group 1, animals developed severe NEC (mean NEC score, 3.28 +/- 0.32; mean MPO, 65.85 +/- 9.46). In group 2, animals developed mild NEC (mean NEC score, 1.72 +/- 0.41; mean MPO, 34.33 +/- 9.69; P < .05). In group 3, no NEC was induced (mean NEC score, 0.0 +/- 0; mean MPO, 6 +/- 1.32; P < .05). CONCLUSION: Tumor necrosis factor alpha antibody may have an attenuating effect on experimental NEC in rats.

Animals↗

Heparin-binding epidermal growth factor-like growth factor decreases the incidence of necrotizing enterocolitis in neonatal rats.

PURPOSE: We have previously demonstrated that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent intestinal cytoprotective agent. The aim of this study was to determine the effect of enterally administered HB-EGF on the incidence of necrotizing enterocolitis (NEC) in neonatal rats. METHODS: Necrotizing enterocolitis was induced in neonatal rats delivered by C-section on day 21 of gestation by exposure to repeated cycles of hypoxia and hypothermia plus administration of hypertonic formula feeding (HHHTF) plus enteral administration of lipopolysaccharide (LPS) (2 mg/kg). Neonatal rats were randomly assigned to breast-feeding, hypertonic formula feeding, HHHTF + LPS, and HHHTF + LPS with HB-EGF (600 mug/kg) supplementation in the formula. Animals were monitored until 96 hours of life and assessed for death, histological NEC, and intestinal mucosal permeability. RESULTS: The incidence of NEC in the HHHTF group was higher than that in the breast-feeding or hypertonic formula feeding groups. With administration of HB-EGF, the incidence and severity of NEC were significantly decreased. Administration of HB-EGF also increased rat pup survival rate and extended survival time. In addition, treatment with HB-EGF significantly decreased intestinal permeability to fluorescein isothiocyanate-dextran. CONCLUSIONS: We conclude that HB-EGF reduces the incidence and severity of NEC in a neonatal rat model, with simultaneous preservation of gut barrier integrity. These results support our contention that HB-EGF administration may represent a useful therapeutic and prophylactic therapy for the treatment of NEC.

Administration, Oral↗