Jianling Xie

Shiga Toxin-Producing Escherichia coli Infection, Antibiotics, and Risk of Developing Hemolytic Uremic Syndrome: A Meta-Analysis

BACKGROUND Antibiotic administration to individuals with Shiga toxin-producing Escherichia coli (STEC) infection remains controversial. We assessed if antibiotic administration to individuals with STEC infection is associated with development of hemolytic uremic syndrome (HUS). METHODS The analysis included studies published up to 29 April 2015, that provided data from patients (1) with STEC infection, (2) who received antibiotics, (3) who developed HUS, and (4) for whom data reported timing of antibiotic administration in relation to HUS. Risk of bias was assessed; strength of evidence was adjudicated. HUS was the primary outcome. Secondary outcomes restricted the analysis to low-risk-of-bias studies employing commonly used HUS criteria. Pooled estimates of the odds ratio (OR) were obtained using random-effects models. RESULTS Seventeen reports and 1896 patients met eligibility; 8 (47%) studies were retrospective, 5 (29%) were prospective cohort, 3 (18%) were case-control, and 1 was a trial. The pooled OR, including all studies, associating antibiotic administration and development of HUS was 1.33 (95% confidence interval [CI], .89-1.99; I(2) = 42%). The repeat analysis including only studies with a low risk of bias and those employing an appropriate definition of HUS yielded an OR of 2.24 (95% CI, 1.45-3.46; I(2) = 0%). CONCLUSIONS Overall, use of antibiotics was not associated with an increased risk of developing HUS; however, after excluding studies at high risk of bias and those that did not employ an acceptable definition of HUS, there was a significant association. Consequently, the use of antibiotics in individuals with STEC infections is not recommended.

Associations Between Hydration Status, Intravenous Fluid Administration, and Outcomes of Patients Infected With Shiga Toxin–Producing Escherichia coli: A Systematic Review and Meta-analysis

Importance The associations between hydration status, intravenous fluid administration, and outcomes of patients infected with Shiga toxin–producing Escherichia coli (STEC) remain unclear. Objective To determine the relationship between hydration status, the development and severity of hemolytic uremic syndrome (HUS), and adverse outcomes in STEC-infected individuals. Data Sources MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials via the OvidSP platform, PubMed via the National Library of Medicine, CINAHL Plus with full text, Scopus, Web of Science, ClinicalTrials.gov, reference lists, and gray literature were systematically searched. Study Selection Two reviewers independently identified studies that included patients with hydration status documentation, proven or presumed STEC infection, and some form of HUS that developed. No language restrictions were applied. Data Extraction and Synthesis Two reviewers independently extracted individual study data, including study characteristics, population, and outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale; strength of evidence was adjudicated using the Grading of Recommendations Assessment, Development, and Evaluation method. Meta-analyses were conducted using random-effects models. Main Outcomes and Measures Development of HUS, complications (ie, oligoanuric renal failure, involvement of the central nervous system, or death), and interventions (ie, renal replacement therapy). Results Eight studies comprising 1511 patients (all children) met eligibility criteria. Unpublished data were provided by the authors of 7 published reports. The median risk-of-bias score was 7.5 (range, 6-9). No studies evaluated the effect of hydration during STEC infections on the risk for HUS. A hematocrit value greater than 23% as a measure of hydration status at presentation with HUS was associated with the development of oligoanuric HUS (OR, 2.38 [95% CI, 1.30-4.35]; I2 = 2%), renal replacement therapy (OR, 1.90 [95% CI, 1.25-2.90]; I2 = 17%), and death (OR, 5.13 [95% CI, 1.50-17.57]; I2 = 55%). Compared with putatively hydrated patients, clinically dehydrated patients had an OR of death of 3.71 (95% CI, 1.25-11.03; I2 = 0%). Intravenous fluid administration up to the day of HUS diagnosis was associated with a decreased risk of renal replacement therapy (OR, 0.26 [95% CI, 0.11-0.60]). Conclusions and Relevance Two predictors of poor outcomes for STEC-infected children were identified: (1) the lack of intravenous fluid administration prior to establishment of HUS and (2) a higher hematocrit value at presentation. These findings point to an association between dehydration and adverse outcomes for children with HUS.

Enteropathogen detection in children with diarrhoea, or vomiting, or both, comparing rectal flocked swabs with stool specimens: an outpatient cohort study

BACKGROUND Enteropathogen detection traditionally relies on diarrhoeal stool samples, but these are inconvenient to collect if they are not immediately available, leading to suboptimum return rates of samples and delayed or missed diagnostic opportunities. We sought to compare the enteropathogen yields of rectal swabs and stool specimens in children with diarrhoea or vomiting, or both. METHODS The Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) did a study in three outpatient cohorts in Calgary and Edmonton (AB, Canada)-children enrolled in the Pediatric Emergency Research Canada emergency departments, children receiving routine vaccinations at a Calgary health clinic, and symptomatic children who met criteria for treatment at home. Eligible participants were children younger than 18 years, with at least three episodes of vomiting or diarrhoea in the preceding 24 h and fewer than 7 days of symptoms. After excluding those enrolled within the previous fortnight, unable to follow-up, or having psychiatric illness, neutropenia, or requiring emergent care, we attempted to collect rectal swabs and stool from all participants. Specimens were tested with the multianalyte assay Luminex xTAG Gastrointestinal Pathogen Panel, an in-house five-virus panel and bacterial culture. Primary outcomes were comparative yield (calculated as the proportion of submitted paired specimens only in which at least one pathogen was identified) and overall yield (which calculated the proportion of study participants in whom at least one pathogen was identified in all specimens, where unsubmitted specimens were analysed as negative). We used McNemars test to do pathogen-specific analyses, and generalised estimating equations (GEE) for the global (ie, any) pathogen analyses, with adjustments made for the presence of diarrhoea, location, and their interactions with specimen type. FINDINGS Between Dec 12, 2014, and Aug 31, 2016, we studied 1519 eligible participants, 1147 (76%) of whom provided stool specimens and 1514 (>99%) provided swab specimens. 871 (76%) of 1147 stool specimens and 1024 (68%) of 1514 swabs were positive for any pathogen (p<0·0001). Comparative yield adjusted odds ratios (ORs) for stool specimens relative to swabs were 1·24 (95% CI 1·11-1·38) in children with diarrhoea at presentation and 1·76 (1·47-2·11) in children without diarrhoea. GEE analysis identified an interaction between the presence of diarrhoea and specimen type (p=0·0011) and collection location (p=0·0078). In an overall yield analysis, pathogen yield was 57% (871 of 1519 children) for stool specimens and 67% (1024 of 1519 children) for rectal swabs, with an unadjusted OR of 0·65 (95% CI 0·59-0·72) for stool relative to swab. INTERPRETATION Rectal swabs should be done when enteropathogen identification and rapid detection are needed, appropriate molecular diagnostic technology is available, and a stool specimen is not immediately available. In view of their high yield, we urge that the recommendation against the use of rectal swabs as diagnostic specimens be reconsidered. FUNDING Alberta Innovates-Health Solutions Team Collaborative Research Innovation Opportunity.

Province-Wide Review of Pediatric Shiga Toxin-Producing Escherichia coli Case Management

Objective To identify the gaps in the care of children infected with Shiga toxin‐producing Escherichia coli (STEC), we sought to quantitate care received and management timelines. Such knowledge is crucial to the design of interventions to prevent the development of hemolytic uremic syndrome (HUS). Study design We conducted a retrospective case‐series study of 78 children infected with STEC in Alberta, Canada, through the linkage of microbiology and laboratory results, telephone health advice records, hospital charts, physician billing submissions, and outpatient antimicrobial dispensing databases. Outcomes were the time intervals between initial presentation and reporting of positive culture result and symptom onset to HUS and to describe the proportions that had baseline blood work performed and received antibiotics. Results Seventy‐eight children infected with STEC were identified; 13% (10/78) developed HUS. Median time from initial presentation to laboratory stool sample receipt was 33 hours (IQR 18, 42); time to positive culture was 120 hours (IQR 86, 205). Time from symptom onset to HUS diagnosis was 188 ± 37 hours. Baseline blood tests were obtained in 74% (58/78) of infected children. Antibiotics were administered to 50% (5/10) of those who developed HUS and 22% (15/78) of those who did not; P = .11. The provincial telephone advice system received 31 calls regarding 24 children infected with STEC; 23% (7/31) of callers were recommended to seek emergency department care. Conclusions A significant proportion of children developed HUS following multiple interactions with the health care system. Delays in the confirmation of STEC infection occurred. There are numerous opportunities to improve the timing, monitoring, and interventions in children infected with STEC.

Management of Shiga toxin producing Escherichia coli-infected children: A multi-national, multi-specialty survey: Bloody diarrhoea and E. coli Infection

Research has highlighted the potential role that hydration status may play in predicting outcomes in Shiga toxin‐producing Escherichia coli (STEC)‐infected children. Because little is known about the management of STEC‐infected children in the pre‐haemolytic uremic syndrome phase, we compared paediatric emergency medicine and nephrologist‐stated management approaches to STEC‐infected children.

Gastroenteritis Severity: A Prospective Cohort Comparison of Children in Emergency Department and Home Settings

Abstract Background While nearly 2 million children are brought to emergency department (ED) annually due to vomiting and/or diarrhea from acute gastroenteritis (AGE), it is estimated that 90% of AGE cases do not seek medical care. We sought to determine whether the disease severity and enteropathogen burden of disease of children with AGE brought for ED care is different from those cared for at home. Methods Subjects were prospectively recruited by the APPETITE team in pediatric EDs in 2 urban centers and via HealthLink, a province-wide nurse telephone advice line. Eligibility criteria included: < 18 years old, AGE defined by ≥ 3 episodes of vomiting or diarrhea in the preceding 24 hours, and < 7 days of symptoms. The primary outcome was index encounter disease severity quantified using the modified Vesikari Scale (MVS) score. To eliminate the impact of the index encounter on the score we excluded the index ED visit and intervention from all calculations. Secondary objectives included the enteropathogen burden of disease. Two rectal swabs and stool were collected and tested for enteropathogens by enteric bacterial culture, Luminex xTAG GPP, and a 5-virus in-house RT-qPCR panel. Results Between December 9, 2014 and December 31, 2016, 1,623 participants were enrolled with 81.5% from the EDs. Median age was 20.1 months. Children who went to ED were less likely to have a family physician (62 vs. 82%, P < 0.001), more likely to have clinical dehydration (Clinical Dehydration Scale score 3 vs 1, P < 0.001) and vomiting (91 vs. 85%, P = 0.004), previously received IV fluids (4.1 vs. 0.7%, P = 0.001) or been admitted (5.4 vs. 1.3%, P = 0.002). The MVS score was similar between groups when the contribution of the index visit to the score was excluded (8.1 vs. 7.8, P = 0.15). Participants recruited in the ED were not significantly more likely to have bacterial pathogens (8.0 vs. 3.7%, P = 0.09) but were less likely to have viral pathogens identified (64.1 vs. 80.7, P < 0.001). Conclusion Children presenting for ED care had disease severity scores that were similar to children managed at home when the contribution of the index ED visit was accounted for. Viral pathogens were more common in AGE receiving care at home while those presenting to the ED and potentially have a clinically greater likelihood of having a bacterial enteropathogen. Disclosures All authors: No reported disclosures.

Iatrogenic Dysnatremias in Children with Acute Gastroenteritis in High-Income Countries: A Systematic Review

Background Acute gastroenteritis (AGE) causing dehydration with or without dysnatremias is a common childhood health challenge. While it is accepted that oral rehydration therapy is preferred, clinical factors or parent and healthcare provider preferences may lead to intravenous rehydration (IVR). Isotonic solutions are increasingly recommended in most scenarios requiring IVR. Nevertheless, children with AGE, having ongoing losses of water and electrolytes, represent a unique population. Objectives To evaluate the association between acquired dysnatremias and IVR in children with AGE. Methods A systematic search of MEDLINE database was conducted through September 14, 2016. Observational studies and clinical trials conducted in high-income countries were included. The Grades of Recommendation, Assessment, Development, and Evaluation approach was used to evaluate the overall quality of evidence for each outcome. Results 603 papers were identified of which 6 were included (3 randomized controlled trials and 3 observational studies). Pooling of patient data was not possible due to significantly different interventions or exposures. Single studies results demonstrated that within 24 h, administration of isotonic saline was not associated with a significant decline in serum sodium while hypotonic solutions (0.2–0.45% saline) were associated, in one study, with mean serum sodium declines from 1.3 mEq/L (139.2, SD 2.9–137.9, SD 2.5) in 133 young infants (aged 1–28 months), to 5.7 (SD 3.1) mEq/L in a subgroup of 18 older children (age mean 5.8, SD 2.7 years). Both isotonic and hypotonic saline were shown to be associated with improvement of baseline hyponatremia in different studies. Baseline hypernatremia was corrected within 4–24 h in 81/83 (99.6%) children using hypotonic saline IVR. Conclusion There is a paucity of publications assessing the risk for acquired dysnatremias associated with IVR in children with AGE. Current high-quality evidence suggests that, short-term use of isotonic solutions is safe and effective in most children with AGE; hypotonic solutions may also be appropriate in some subpopulations, however, the quality of available evidence is low to very low. Further research investigating outcomes associated with IVR use beyond 24 h focusing on specific age groups is required.