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A pilot study of seven days of ceftriaxone therapy for children with Salmonella enterocolitis.

BACKGROUND: The most effective therapy for non-typhoid Salmonella enterocolitis is still unknown. Traditionally, unless extraintestinal complications are present, antimicrobial drugs are not recommended, since earlier trials have shown that antibiotics such as ampicillin, chloramphenicol, or co-trimoxazole, do not shorten the duration of diarrhea and may even prolong convalescent fecal carriage of the bacteria. However, the recently-developed third generation cephalosporin ceftriaxone has been used successfully in the treatment of typhoid fever and other systemic salmonellosis. A controlled, pilot study was therefore undertaken to evaluate the efficacy of intravenous ceftriaxone in the treatment of children with non-typhoid Salmonella enterocolitis. METHODS: Fifteen children with Salmonella enterocolitis and bacteremia who were eligible for antibiotic therapy were given ceftriaxone intravenously for 7 days and 15 children with enterocolitis but without bacteremia who were admitted for supportive treatment during the study period were selected as the control group. Available stool samples collected on days, 7, 14, and 30 after the completion of the drug therapy were checked for the presence of the bacteria using polymerase chain reaction (PCR) and culture methods. RESULTS: The result showed that the duration of diarrhea was not significantly affected by ceftriaxone treatment. However, the difference in the rate of clearance of Salmonella from stools, as defined by negative stool cultures and PCR, was statistically significant between the two groups on posttreatment days 7 and 14. Only one patient given ceftriaxone was shown to have recrudescence of the bacteria in feces on day 14. One month after therapy, PCR was positive in two of the ten cases tested and one of these two experienced a relapse of diarrhea, whereas bacterial carriage was maintained in 63% of the control patients. CONCLUSION: A prompt eradication of Salmonella in feces was observed in most of the patients treated with ceftriaxone in this study. If further studies confirm the efficacy of this therapy and the risk of inducing drug resistance is minimal, the epidemiologic problem created by convalescent fecal bacterial carriage may justify a short-course of ceftriaxone therapy for children with Salmonella enterocolitis.

Ceftriaxone↗

Current prognosis in necrotizing enterocolitis with portal vein gas.

OBJECTIVE: To investigate anecdotal reports that portal vein gas in necrotizing enterocolitis is no longer associated with a poor prognosis. PATIENTS AND METHODS: Twelve cases of neonatal necrotizing enterocolitis with portal vein gas from 1988 to 1994 were identified retrospectively from the radiology dictation system in a large university hospital. RESULTS: Two distinct groups of patients with portal vein gas in necrotizing enterocolitis were identified. In 3 of the 12 children, portal vein gas was identified on abdominal films after the diagnosis of necrotizing enterocolitis. These infants had no serious sequelae. By contrast, in 8 of the 9 infants with portal vein gas seen on the initial film at presentation, emergent surgery was required. Four of these infants died from complications of necrotizing enterocolitis and 2 died from sepsis related to total parenteral nutrition. The remaining 2 children have short bowel syndrome, 1 is dependent on total parenteral nutrition and 1 requires continuous gastrostomy tube feedings. CONCLUSION: The children with portal vein gas on the initial abdominal film continue to have a guarded prognosis.

Enterocolitis, Pseudomembranous↗

Association of Clostridium difficile with enterocolitis and lactose intolerance in a foal.

Diagnoses of Clostridium difficile enterocolitis and lactose intolerance were made in a neonatal foal with persistent diarrhea. It was determined that the foal had lactose intolerance on the basis of the results of a lactose tolerance test, and a diagnosis of C difficile enterocolitis was subsequently made. The foal responded to oral administration of metronidazole and lactase. Lactose intolerance is a secondary problem most commonly associated with rotavirus infection, but it can be caused by any condition affecting the small intestine. Because C difficile can affect the small intestine in foals, it was presumably the cause of the lactose intolerance in this foal with persistent diarrhea. Oral administration of lactase was not initially successful in this foal, most likely because of ongoing C difficile enterocolitis. Presumably, metronidazole was an effective treatment for C difficile enterocolitis and administration of lactase allowed for normal digestion of milk until endogenous lactose production returned. Clostridium difficile enterocolitis and lactose intolerance should be considered as differential diagnoses in neonatal foals with diarrhea, especially when the foal is bright and alert.

Animals↗

Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth-weight neonates.

BACKGROUND: Necrotizing enterocolitis (NEC) is the most common emergency of the gastrointestinal tract occurring in the neonatal period. There have been published reports which suggest that oral immunoglobulins IgA and IgG produce an immunoprotective effect in the gastrointestinal mucosa. This systematic review was undertaken to clarify the issue. OBJECTIVES: To assess whether oral immunoglobulin administered to preterm and low birth-weight neonates reduces the incidence of necrotizing enterocolitis without adverse effects. SEARCH STRATEGY: The databases MEDLINE, CINAHL, EMBASE (1966 to October 26, 2003) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2003) were searched. Proceedings of the Perinatal Society of Australia and New Zealand were hand searched. The computer neonatal discussion site 'Nicu Net' was also used. Additionally, all references in the identified trials were checked and authors were contacted to request any additional published or unpublished data. No new trials were identified. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials where oral immunoglobulins were used as prophylaxis against necrotizing enterocolitis in preterm (<37 weeks gestation) and/or low birth-weight (<2500 gms) neonates. DATA COLLECTION AND ANALYSIS: The procedures of the Cochrane Neonatal Review Group (CNRG) were used. The two reviewers independently assessed the trials for their methodological quality and subsequent inclusion in the review. Relative risk (RR), risk difference (RD), and number needed to treat (NNT) were used in the analysis. MAIN RESULTS: Five studies on oral immunoglobulin for the prevention of necrotizing enterocolitis were identified of which three met the inclusion criteria. In this review of the three eligible trials (including a total of 2095 neonates) the oral administration of IgG or an IgG/IgA combination did not result in a significant reduction in the incidence of definite NEC [RR 0.84 (95% CI 0.57, 1.25), RD -0.01 (95% CI -0.03, 0.01)], suspected NEC [RR 0.84 (95% CI 0.49, 1.46), RD -0.01 (95% CI -0.02, 0.01)], need for surgery [RR 0.21 (95% CI 0.02, 1.75), RD -0.03 (95% CI -0.06, 0.00)] or death from NEC [RR 1.10 (95% CI 0.47, 2.59), RD 0.00 (95% CI -0.01, 0.01)]. REVIEWER'S CONCLUSIONS: Based on the available trials, the evidence does not support the administration of oral immunoglobulin for the prevention of NEC. There are no randomised controlled trials of oral IgA alone for the prevention of NEC.

Administration, Oral↗

Selective management of patients with neutropenic enterocolitis using peritoneal lavage.

Neutropenic enterocolitis is a symptom complex of fever, abdominal pain, distention, nausea, vomiting, diarrhea, and bloody stools occurring in a patient with a low neutrophil count and is most often seen in patients with acute leukemia after a course of chemotherapy. In most cases, neutropenic enterocolitis is a self-limited condition, but complications of transmural intestinal necrosis and bowel perforation may occur in a small number of patients. Surgical management should be reserved for those patients with bowel wall necrosis or perforation; however, early identification of these patients is difficult. We report our experience with the use of diagnostic peritoneal lavage in three patients with the symptoms and signs of neutropenic enterocolitis. In each case, Gram's stain of lavage fluid revealed no evidence of polymicrobial contamination of the peritoneal cavity. All three patients were managed medically, with resolution of their abdominal symptoms. Peritoneal lavage is helpful in excluding bowel perforation and avoiding unnecessary surgical intervention in patients with neutropenic enterocolitis.

Adult↗

IL-15 is elevated in the patients of postoperative enterocolitis.

Serum interleukin 15 (IL-15) levels were measured in 77 patients who were consecutively admitted to our intensive care unit. Postoperative enterocolitis occurred in four patients and Methicillin-resistant Staphylococcus aureus (MRSA), but not Clostridium difficile, was identified in the faecal specimens from these patients. The IL-15 levels in the patients with MRSA enterocolitis were significantly elevated compared with those of other MRSA infections without enterocolitis including pneumonia (n=6) and cholangitis (n=1), and other MRSA non-colonized patients (n=66) (21.2+/-5.2 pg/ml vs 4.3+/-0.2, 4.3+/-0.5). Notably, an increase in serum IL-15 was observed just before clinical manifestation of severe diarrhoea. Our findings suggest that IL-15 may be associated in the pathogenesis of postoperative enterocolitis and its serum level may be a severity indicator of the disease.

Adult↗

Prophylaxis of necrotizing enterocolitis by oral IgA-IgG: review of a clinical study in low birth weight infants and discussion of the pathogenic role of infection.

Necrotizing enterocolitis, a severe gastrointestinal disease in the neonatal period, affects primarily premature infants. Perinatal complications that predispose the neonate to systemic hypoxia are frequent in infants with necrotizing enterocolitis. Ischemia of the intestinal mucosa may facilitate the invasion of enteric microorganisms in stressed low birth weight infants. Geographical and temporal clustering of outbreaks of the disease and the termination of epidemics by standard infection control underline the importance of infectious agents in the development of this disease. Several studies have established the immunoprotective effect of orally administered antibodies against infection of the gastrointestinal mucosa in children and adults. Anecdotal evidence suggested that feeding of human immune globulin might have a positive effect on the incidence of necrotizing enterocolitis in premature infants. This paper reviews a prospective, randomized, controlled trial of the efficacy of an oral immune globulin preparation (published in detail in the New England Journal of Medicine, Vol. 319, pp 1-7, 1988) and discusses the pathogenic role of infection in necrotizing enterocolitis.

Administration, Oral↗

Prevention of necrotizing enterocolitis in the rat with prenatal cortisone.

Cortisone acetate is known to accelerate maturation of the immature intestine. The effect of prenatal administration of cortisone acetate on the morbidity and mortality of necrotizing enterocolitis was examined in a rat pup model. Pregnant rats were administered cortisone acetate, 20 mg/100 g of body weight, or normal saline by daily IP injection from day 18-21 of gestation. Rat pups were taken from the mothers before suckling was initiated, fed a simulated rat milk formula, and subjected to daily ischemic insults to produce an animal model of necrotizing enterocolitis. Both morbidity and the mortality rates were significantly improved with prenatal cortisone treatment. Maturation of the intestinal mucosal barrier was accelerated with the cortisone treatment as measured by decreased serum concentrations of a fed antigen, ovalbumin. Aerobic bacterial colonization of the small intestine and translocation of bacteria to the liver were decreased in the pups pretreated with steroids. These changes observed in a rat model of necrotizing enterocolitis may explain the decreased incidence of necrotizing enterocolitis in human infants born to mothers who received corticosteroids late in gestation.

Animals↗

Rectal irrigations for the prevention of postoperative enterocolitis in Hirschsprung's disease.

The purpose of this clinical trial was to examine the role of rectal irrigations in the prevention of postoperative enterocolitis in children with Hirschsprung's disease. Over the past 22 years 177 children had surgical treatment for Hirschsprung's disease at a single pediatric hospital. Five children have died of other causes. Of the remaining 172 patients, follow-up clinical information was obtained from 135 (78%). In 1989, all of the children undergoing surgical reconstruction for Hirschsprung's disease were placed on routine postoperative rectal irrigations with normal saline. The parents were instructed in the irrigation technique before leaving the hospital. Irrigations were started 1 to 2 weeks postoperatively and were performed two times a day for 3 months, then once a day for an additional 3 months. There were no complications from the irrigations themselves. A previous report from the authors' institution has documented five sudden deaths over the past 22 years from fulminant postoperative enterocolitis. These five children all had an unremarkable postoperative recovery, then developed a rapidly progressive diarrheal illness. All of these deaths occurred before the institution of routine postoperative irrigations. Of the 135 patients in this review, 40 had the postoperative rectal irrigations. The remaining 95 children serve as historical controls. Data analysis showed that 34 of the 95 children in the nonirrigation cohort developed postoperative enterocolitis compared with 3 of 40 in the rectal irrigation cohort; P < .001 using Fisher's exact test. In the authors' experience, routine postoperative rectal irrigations have significantly decreased the incidence and severity of enterocolitis in children after surgical correction of Hirschsprung's disease.

Child↗

Breast milk and neonatal necrotising enterocolitis.

In a prospective multicentre study on 926 preterm infants formally assigned to their early diet, necrotising enterocolitis developed in 51 (5.5%). Mortality was 26% in stringently confirmed cases. In exclusively formula-fed babies confirmed disease was 6-10 times more common than in those fed breast milk alone and 3 times more common than in those who received formula plus breast milk. Pasteurised donor milk seemed to be as protective as raw maternal milk. Among babies born at more than 30 weeks' gestation confirmed necrotising enterocolitis was rare in those whose diet included breast milk; it was 20 times more common in those fed formula only. Other risk factors included very low gestational age, respiratory disease, umbilical artery catheterisation, and polycythaemia. In formula-fed but not breast-milk-fed infants, delayed enteral feeding was associated with a lower frequency of necrotising enterocolitis. With the fall in the use of breast milk in British neonatal units, exclusive formula feeding could account for an estimated 500 extra cases of necrotising enterocolitis each year. About 100 of these infants would die.

Enterocolitis, Pseudomembranous↗

Gemcitabine associated vasculitis leading to necrotizing enterocolitis and death in women undergoing primary treatment for epithelial ovarian/peritoneal cancer.

We present two patients who developed necrotizing enterocolitis following their first cycle of chemotherapy for epithelial ovarian/peritoneal cancer. After optimal cytoreductive surgery, both women received gemcitabine as part of a chemotherapy protocol. One patient developed necrotizing enterocolitis, 1 day after chemotherapy and the other 8 days after chemotherapy. The first patient succumbed to the enterocolitis despite aggressive supportive care. The second patient succumbed despite both aggressive supportive care and surgical intervention. Pathologic review for both patients revealed a drug induced vasculitis causing necrotizing enterocolitis.

Aged↗

Nitroglycerin attenuates the bowel damage of necrotizing enterocolitis in a rabbit model.

Endogenous enteric nitric oxide has multiple functions. Enteric nitric oxide may be diminished in the premature infant and may therefore predispose the immature intestine to injury. The aim of this study was to determine if the infusion of a nitric oxide donor (nitroglycerin) would attenuate intestinal damage in a rabbit model of necrotizing enterocolitis. Transmural injection of rabbit intestinal loops with an acidified solution of casein and calcium gluconate simulates certain aspects of necrotizing enterocolitis. After injection of acidified casein solution into rabbit intestinal loops, twelve rabbits were randomly divided into two groups: six received maintenance fluids only and six received maintenance fluids and a nitroglycerin infusion adjusted to maintain mean arterial pressure 10 mm Hg below baseline (range, 2 to 12 micrograms/kg/min). After 3 hours, the rabbits were killed, and the intestinal tissue graded histologically. Intestinal damage in the nitroglycerin-treated rabbits was significantly less than that of untreated controls (mean histological grade of 0.39 v 1.48, P < .001). In this rabbit model of necrotizing enterocolitis, infusion of the nitric oxide donor nitroglycerin significantly attenuates intestinal damage. We speculate that enteric nitric oxide deficiency, as may exist in the preterm infant, predisposes the intestine to necrotizing enterocolitis.

Animals↗

Role of delayed feeding and of feeding increments in necrotizing enterocolitis.

In spite of a number of studies on necrotizing enterocolitis, there remains controversy concerning prevention regimens, especially with regard to enteral alimentation. This report is of a matched case-control study of the relationship of necrotizing enterocolitis to timing of first feeding, size of feeding volumes and increments, and a risk factor index in 59 case patients with necrotizing enterocolitis and 59 matched control patients. Comparison with control patients showed that case patients were fed earlier, received full-strength formula sooner, and received larger feeding volumes and increments. More highly stressed infants, as measured by the risk index, were more vulnerable to larger feeding increments. Among case patients there was significant correlation of age at first feeding and age at diagnosis (p < 0.0001) even after control for birth weight and risk index score, indicating that delayed feeding was related to delayed onset of disease. These analyses support the theory that earlier, more rapid feeding places stressed infants at greater risk for the development of necrotizing enterocolitis, and that infants with more severe respiratory problems are more vulnerable to such feeding practices.

Birth Weight↗

Necrotizing enterocolitis in low-birth-weight infants fed an elemental formula.

The incidence of necrotizing enterocolitis in the newborn infant has increased within the same time period that increasing emphasis has been placed on oral alimentation of very small infants. A prospective investigation was conducted to determine the nutritional efficacy as well as the incidence of necrotizing enterocolitis of a standard cow milk formula compared with an elemental formula. Sixteen infants who weighed less than 1,200 gm were randomized and fed one of the two formulas. The clinical status of the two groups was similar. Seven of eight (87.5%) infants fed the elemental formula and two of eitht (25%) fed the standard cow milk formula developed necrotizing enterocolitis (p less than 0.02). The hypertonicity of the elemental diet may have contributed to the increased incidence of necrotizing enterocolitis in infants fed this formula.

Animals↗

Heat-stable enterotoxigenic Escherichia coli and necrotizing enterocolitis: lack of an association.

During an outbreak of diarrhea in a special care nursery caused by heat-stable enterotoxigenic Escherichia coli (serotype 078:H11:K80), nine (4.3%) of the 205 infants in the nursery developed necrotizing enterocolitis. Cases of necrotizing enterocolitis were not significantly more common in infants colonized or infected with these organisms; heat-stable enterotoxigenic E. coli was isolated from 5(56%) of nine cases of necrotizing ecterocolitis and from 27(38%) of the 71 infants without necrotizing enterocolitis who were also cultured. Our findings suggest that caution should be taken in implicating enterotoxigenic E. coli as a cause of necrotizing enterocolitis.

Animals↗

Necrotizing enterocolitis can be caused by polycythemic hyperviscosity in the newborn dog.

Although necrotizing enterocolitis has been associated with polycythemia in human infants, a causal relationship has not been established. Forty-six unanesthetized puppies were studied (age 6 to 14 days). Normovolemic polycythemia (Hct 0.70) was induced in 19 pups by exchange transfusion with 75 ml/kg packed red blood cells. Hypervolemic polycythemia (Hct 0.70) was induced in 14 pups by transfusion with 50 ml/kg RBC. Thirteen pups received exchange transfusion with whole blood and served as controls (Hct 0.40). Gross autopsy was performed on all pups 24 hours after transfusion or at death. Necrotizing enterocolitis was defined as areas of violaceous discoloration of the bowel associated with blood in the intestinal lumen. Although lesions appeared throughout the bowel in some pups, involvement of the distal small bowel was most common. Diagnosis was confirmed by microscopic examination. Both gross and microscopic lesions appeared similar to those in necrotizing enterocolitis in human infants. The disorder was seen in 11 of 19 pups with normovolemic polycythemia, eight of 14 pups with hypervolemic polycythemia, and only one of 13 control animals (P less than 0.01). Polycythemia can cause necrotizing enterocolitis in the newborn dog.

Animals↗

Selective kallikrein-kinin system activation in inbred rats differentially susceptible to granulomatous enterocolitis.

BACKGROUND & AIMS: Crohn's disease is characterized by unrestrained inflammation with a genetic component. Genetic susceptibility and activation of the kalli-krein-kinin (contact) system were investigated in experimental enterocolitis and extraintestinal inflammation induced by bacterial polymers. METHODS: Kinetics of inflammation in inbred Lewis and Buffalo rats injected subserosally with peptidoglycan-polysaccharide polymers were correlated with in vivo and in vitro activation of the contact system. RESULTS: Lewis rats had a biphasic course of enterocolitis. Acute inflammation peaked 1 day after injection, gradually decreasing until day 14 when intestinal inflammation spontaneously reactivated and persisted for 16 weeks, accompanied by arthritis, granulomatous hepatitis, anemia, and leukocytosis. Self-limited acute enterocolitis in Buffalo rats resolved by 24 days without extraintestinal involvement. Consumption of the precursor proteins prekalli-krein and high-molecular-weight kininogen indicated activation of the plasma contact system in Lewis rats and closely correlated with chronic intestinal inflammation. Contact system activation did not occur in Buffalo rats, even during acute inflammation. In vitro studies showed a decreased rate of kininogen cleavage in Buffalo plasma. CONCLUSIONS: Selective in vivo and in vitro activation of the contact system in susceptible Lewis rats suggests that this pathway is one determinant of genetic susceptibility to granulomatous enterocolitis and systemic complications.

Acute-Phase Proteins↗

The effects of Lactobacillus strains and oat fiber on methotrexate-induced enterocolitis in rats.

BACKGROUND & AIMS: Administration of methotrexate to rats on an elemental diet results in severe enterocolitis and death. Lactobacilli, an integral part of the healthy gastrointestinal microecology, may provide therapeutic benefits to help the recovery from enterocolitis. The purpose of this study was to evaluate the effects of lactobacilli and oatbase on methotrexate-induced enterocolitis in rats. METHODS: Rats received continuous intragastric infusion of elemental diet or with supplementation of oatbase, Lactobacillus reuteri R2LC, and Lactobacillus plantarum DSM 9843, with and without fermentation, from the beginning of the study. Methotrexate (20 mg/kg) was injected intraperitoneally on day 3, and the sampling was performed on day 6. RESULTS: Lactobacilli and oatbase decreased body weight loss and intestinal permeability and increased bowel mucosal mass in enterocolitic rats. Administration of lactobacilli, but not oatbase, decreased the intestinal myeloperoxidase level, reestablished intestinal microecology, and reduced bacterial translocation to extraintestinal sites. Both lactobacilli and oatbase reduced plasma endotoxin levels. The effects of lactobacilli were greater with fermentation than without fermentation or oatbase alone, and L. plantarum was more effective in reducing intestinal pathogens than L. reuteri. CONCLUSIONS: Exogenous administration of lactobacilli, especially L. plantarum with fermentation, is helpful in reducing the severity of enterocolitis in rats.

Animals↗