Eileen J. Klein

Relative Nephroprotection During Escherichia coli O157:H7 Infections: Association With Intravenous Volume Expansion

Objective. The hemolytic uremic syndrome (HUS) consists of hemolytic anemia, thrombocytopenia, and renal failure. HUS is often precipitated by gastrointestinal infection with Shiga toxin–producing Escherichia coli and is characterized by a variety of prothrombotic host abnormalities. In much of the world, E coli O157:H7 is the major cause of HUS. HUS can be categorized as either oligoanuric (which probably signifies acute tubular necrosis) or nonoligoanuric. Children with oligoanuric renal failure during HUS generally require dialysis, have more complicated courses, and are probably at increased risk for chronic sequelae than are children who experience nonoligoanuric HUS. Oligoanuric HUS should be avoided, if possible. The presentation to medical care of a child with definite or possible E coli O157:H7 infections but before HUS ensues affords a potential opportunity to ameliorate the course of the subsequent renal failure. However, it is not known whether events that occur early in E coli O157:H7 infections, particularly measures to expand circulating volume, affect the likelihood of experiencing oligoanuric HUS if renal failure develops. We attempted to assess whether pre-HUS interventions and events, especially the volume and sodium content of intravenous fluids administered early in illness, affect the risk for developing oligoanuric HUS after E coli O157:H7 infections. Methods. We performed a prospective cohort study of 29 children with HUS that was confirmed microbiologically to be caused by E coli O157:H7. Infected children were enrolled when they presented with acute bloody diarrhea or as contacts of patients who were known to be infected with E coli O157:H7, or if they had culture-confirmed infection, or if they presented with HUS. HUS was defined as hemolytic anemia (hematocrit <30%, with fragmented erythrocytes on peripheral-blood smear), thrombocytopenia (platelet count of <150000/mm3), and renal insufficiency (serum creatinine concentration that exceeded the upper limit of normal for age). A wide range of pre-HUS variables, including demographic factors, clinical history, medications given, initial laboratory values, and volume and content of parenteral fluid administered, were recorded and entered into analysis. Estimates of odds ratios were adjusted for possible confounding effects using logistic regression analysis. Twenty-nine children who were <10 years old, had HUS confirmed to be caused by E coli O157:H7, and were hospitalized at the Childrens Hospital and Regional Medical Center, Seattle, were studied. The main outcome measured was development of oligoanuric renal failure. Oligoanuria was defined as a urine output <0.5 mL/kg per hour for at least 24 consecutive hours. Results. As a group, the children with oligoanuric renal failure presented to medical attention and were evaluated with laboratory testing later than the children with nonoligoanuric renal failure. On initial assessments, the children with oligoanuric outcomes had higher white blood cell counts, lower platelet counts and hematocrits, and higher creatinine concentrations than the children with nonoligoanuric outcomes, but these determinations probably reflect later points of these initial determinations, often when HUS was already developing. Stool cultures were obtained (medians of 3 vs 2 days, respectively) and positive (medians of 7 vs 4 days, respectively) at later points in illness in the children in the oligoanuric than in the nonoligoanuric group. Intravenous volume expansion began later in illness in the children who subsequently developed oligoanuric renal failure than in those whose renal failure was nonoligoanuric (medians: 4.5 vs 3.0 days, respectively). Moreover, the 13 patients with nonoligoanuric renal failure received more intravenous fluid and sodium before HUS developed (1.7- and 2.5-fold differences, respectively, between medians) than the 16 patients with oligoanuric renal failure. These differences were even greater when the first 4 days of illness were examined, with 17.1- and 21.8-fold differences, respectively, between medians. In a multivariate analysis adjusted for age, gender, antibiotic use, and free water volume administered intravenously to these children during the first 4 days of illness, the amount of sodium infused remained associated with protection against developing oligoanuric HUS. Dialysis was used in each of the children with oligoanuric renal failure and in none of the children with nonoligoanuric renal failure. The median length of stay in hospital after the diagnosis of HUS was 12 days in the oligoanuric group and 6 days in the nonoligoanuric group. Conclusions. Early recognition of and parenteral volume expansion during E coli O157:H7 infections, well before HUS develops, is associated with attenuated renal injury failure. Parenteral hydration in children who are possibly infected with E coli O157:H7, at the time of presentation with bloody diarrhea and in advance of culture results, is a practice that can accelerate the start of volume expansion during the important pre-HUS interval. Rapid assessment of stools for E coli O157:H7 by microbiologists and reporting of presumptive positives immediately can alert practitioners that patients are at risk for developing HUS and can prompt volume expansion in children who are not already being so treated. Our data also suggest that isotonic intravenous solutions might be superior to hypotonic fluids for use as maintenance fluids. Children who are infected with E coli O157:H7 and are given intravenous volume expansion need careful monitoring. This monitoring should be even more assiduous as HUS evolves.

Diarrhea Etiology in a Children's Hospital Emergency Department: A Prospective Cohort Study

BACKGROUND We evaluated the frequency of recovery of pathogens from children with diarrhea who presented to a pediatric emergency department and characterized the associated illnesses, to develop guidelines for performing a bacterial enteric culture. METHODS We conducted a prospective cohort study of all patients with diarrhea who presented to a large regional pediatric emergency department during the period from November 1998 through October 2001. A thorough microbiologic evaluation was performed on stool specimens, and the findings were correlated with case, physician, and laboratory data. RESULTS A total of 1626 stool specimens were studied to detect diarrheagenic bacteria and, if there was a sufficient amount of stool, Clostridium difficile toxin (688 specimens), parasites (656 specimens), and viruses (417 specimens). One hundred seventy-six (47%) of 372 specimens that underwent complete testing yielded a bacterial pathogen (Shiga toxin-producing Escherichia coli, 39 specimens [of which 28 were serotype O157:H7]; Salmonella species, 39; Campylobacter species, 25; Shigella species, 14; and Yersinia enterocolitica, 2), a viral pathogen (rotavirus, 85 specimens; astrovirus, 27; adenovirus, 18; or rotavirus and astrovirus, 8), a diarrheagenic parasite (5 specimens); or C. difficile toxin (46 specimens). Samples from 2 patients yielded both bacterial and viral pathogens. A model to identify predictors of bacterial infection found that international travel, fever, and the passing of >10 stools in the prior 24 h were associated with the presence of a bacterial pathogen. Physician judgment regarding the need to perform a stool culture was almost as accurate as the model in predicting bacterial pathogens. CONCLUSIONS Nearly one-half of the patients who presented to the emergency department with diarrhea had a definite or plausible pathogen in their stool specimens. We were unable to develop a model that was substantially better than physician judgment in identifying patients for whom bacterial culture would yield positive results. The unexpectedly high rate of C. difficile toxin warrants further examination.

Use of Incident Reports by Physicians and Nurses to Document Medical Errors in Pediatric Patients

Objectives. To describe the proportion and types of medical errors that are stated to be reported via incident report systems by physicians and nurses who care for pediatric patients and to determine attitudes about potential interventions for increasing error reports. Methods. A survey on use of incident reports to document medical errors was sent to a random sample of 200 physicians and nurses at a large childrens hospital. Items on the survey included proportion of medical errors that were reported, reasons for underreporting medical errors, and attitudes about potential interventions for increasing error reports. In addition, the survey contained scenarios about hypothetical medical errors; the physicians and nurses were asked how likely they were to report each of the events described. Differences in use of incident reports for documenting medical errors between nurses and physicians were assessed with χ2 tests. Logistic regression was used to determine the association between health care profession type and likelihood of reporting medical errors. Results. A total of 140 surveys were returned, including 74 from physicians and 66 by nurses. Overall, 34.8% of respondents indicated that they had reported <20% of their perceived medical errors in the previous 12 months, and 32.6% had reported <40% of perceived errors committed by colleagues. After controlling for potentially confounding variables, nurses were significantly more likely to report ≥80% of their own medical errors than physicians (odds ratio: 2.8; 95% confidence interval: 1.3–6.0). Commonly listed reasons for underreporting included lack of certainty about what is considered an error (indicated by 40.7% of respondents) and concerns about implicating others (37%). Potential interventions that would lead to increased reporting included education about which errors should be reported (listed by 65.4% of respondents), feedback on a regular basis about the errors reported (63.8%) and about individual events (51.2%), evidence of system changes because of reports of errors (55.4%), and an electronic format for reports (44.9%). Although virtually all respondents would likely report a 10-fold overdose of morphine leading to respiratory depression in a child, only 31.7% would report an event in which a supply of breast milk is inadvertently connected to a venous catheter but is discovered before any breast milk goes into the catheter. Conclusions. Medical errors in pediatric patients are significantly underreported in incident report systems, particularly by physicians. Some types of errors are less likely to be reported than others. Information in incident reports is not a representative sample of errors committed in a childrens hospital. Specific changes in the incident report system could lead to more reporting by physicians and nurses who care for pediatric patients.

Effectiveness of Pentavalent and Monovalent Rotavirus Vaccines in Concurrent Use Among US Children <5 Years of Age, 2009–2011

BACKGROUND We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) visits in US children. METHODS We enrolled children <5 years of age hospitalized or visiting the ED with AGE symptoms from November 2009-June 2010 and from November 2010-June 2011 at 7 medical institutions. Fecal specimens were tested for rotavirus by enzyme immunoassay and genotyped. Vaccination among laboratory-confirmed rotavirus cases was compared with rotavirus-negative AGE controls. Regression models calculated VE estimates for each vaccine, age, ethnicity, genotype, and clinical setting. RESULTS RV5-specific analyses included 359 rotavirus cases and 1811 rotavirus-negative AGE controls. RV1-specific analyses included 60 rotavirus cases and 155 rotavirus-negative AGE controls. RV5 and RV1 were 84% (95% confidence interval [CI], 78%-88%) and 70% (95% CI, 39%-86%) effective, respectively, against rotavirus-associated ED visits and hospitalizations combined. By clinical setting, RV5 VE against ED and inpatient rotavirus-associated visits was 81% (95% CI, 70%-84%) and 86% (95% CI, 74%-91%), respectively. RV1 was 78% (95% CI, 46%-91%) effective against ED rotavirus disease; study power was insufficient to evaluate inpatient RV1 VE. No waning of immunity was evident during the first 4 years of life for RV5, nor during the first 2 years of life for RV1. RV5 provided genotype-specific protection against each of the predominant strains (G1P[8], G2P[4], G3P[8], G12P[8]), while RV1 VE was statistically significant for the most common genotype, G3P[8]. CONCLUSIONS Both RV5 and RV1 significantly protected against medically attended rotavirus gastroenteritis in this real-world assessment.

Diarrhea Etiology in a Pediatric Emergency Department: A Case Control Study

BACKGROUND The etiology of childhood diarrhea is frequently unknown. METHODS We sought Aeromonas, Campylobacter, Escherichia coli O157:H7, Pleisiomonas shigelloides, Salmonella, Shigella, Vibrio, and Yersinia (by culture), adenoviruses, astroviruses, noroviruses, rotavirus, and Shiga toxin-producing E. coli (STEC; by enzyme immunoassay), Clostridium difficile (by cytotoxicity), parasites (by microscopy), and enteroaggregative E. coli (EAEC; by polymerase chain reaction [PCR] analysis) in the stools of 254 children with diarrhea presenting to a pediatric emergency facility. Age- and geographic-matched community controls without diarrhea (n = 452) were similarly studied, except bacterial cultures of the stool were limited only to cases. RESULTS Twenty-nine (11.4%) case stools contained 13 Salmonella, 10 STEC (6 O157:H7 and 4 non-O157:H7 serotypes), 5 Campylobacter, and 2 Shigella. PCR-defined EAEC were present more often in case (3.2%) specimens than in control (0.9%) specimens (adjusted odds ratio [OR], 3.9; 95% confidence interval [CI], 1.1-13.7), and their adherence phenotypes were variable. Rotavirus, astrovirus, and adenovirus were more common among cases than controls, but both groups contained noroviruses and C. difficile at similar rates. PCR evidence of hypervirulent C. difficile was found in case and control stools; parasites were much more common in control specimens. CONCLUSIONS EAEC are associated with childhood diarrhea in Seattle, but the optimal way to identify these agents warrants determination. Children without diarrhea harbor diarrheagenic pathogens, including hypervirulent C. difficile. Our data support the importance of taking into account host susceptibility, microbial density, and organism virulence traits in future case-control studies, not merely categorizing candidate pathogens as being present or absent.

Teaching professionalism to residents.

The need to teach professionalism during residency has been affirmed by the Accreditation Council for Graduate Medical Education, which will require documentation of education and evaluation of professionalism by 2007. Recently the American Academy of Pediatrics has proposed the following components of professionalism be taught and measured: honesty/integrity, reliability/responsibility, respect for others, compassion/empathy, self-improvement, self-awareness/knowledge of limits, communication/collaboration, and altruism/advocacy. The authors describe a curriculum for introducing the above principles of professionalism into a pediatrics residency that could serve as a model for other programs. The curriculum is taught at an annual five-day retreat for interns, with 11 mandatory sessions devoted to addressing key professionalism issues. The authors also explain how the retreat is evaluated and how the retreats topics are revisited during the residency, and discuss general issues of teaching and evaluating professionalism.

Medical error disclosure among pediatricians: choosing carefully what we might say to parents.

OBJECTIVE To determine whether and how pediatricians would disclose serious medical errors to parents. DESIGN Cross-sectional survey. SETTING St Louis, Missouri, and Seattle, Washington. PARTICIPANTS University-affiliated hospital and community pediatricians and pediatric residents. Main Exposure Anonymous 11-item survey administered between July 1, 2003, and March 31, 2004, containing 1 of 2 scenarios (less or more apparent to the childs parent) in which the respondent had caused a serious medical error. MAIN OUTCOME MEASURES Physicians intention to disclose the error to a parent and what information the physician would disclose to the parent about the error. RESULTS The response rate was 56% (205/369). Overall, 53% of all respondents (109) reported that they would definitely disclose the error, and 58% (108) would offer full details about how the error occurred. Twenty-six percent of all respondents (53) would offer an explicit apology, and 50% (103) would discuss detailed plans for preventing future recurrences of the error. Twice as many pediatricians who received the apparent error scenario would disclose the error to a parent (73% [75] vs 33% [34]; P < .001), and significantly more would offer an explicit apology (33% [34] vs 20% [20]; P = .04) compared with the less apparent error scenario. CONCLUSIONS This study found marked variation in how pediatricians would disclose a serious medical error and revealed that they may be more willing to do so when the error is more apparent to the family. Further research on the impact of professional guidelines and innovative educational interventions is warranted to help improve the quality of error disclosure communication in pediatric settings.

Prevalence and Mechanisms of Broad-Spectrum β-Lactam Resistance in Enterobacteriaceae: a Children's Hospital Experience

ABSTRACT The objective of this study was to investigate the trends and patterns of resistance in β-lactamase-producing members of the family Enterobacteriaceae in a childrens hospital over a 9-year period (1999 to 2007). Clinically significant isolates of the Enterobacteriaceae were screened for patterns of broad-spectrum resistance to β-lactams. The strains likely to be resistant were subsequently confirmed by an inhibitor-based disc test. The plasmid-mediated resistance determinants in these isolates were identified by PCR and by in vitro transformation, which successfully reproduced the AmpC phenotype unrestricted by the species of the host organisms. Among 8,048 Enterobacteriaceae isolates belonging to the four chromosomal ampC-negative or -nonfunctional genera, 86 (1.07%) isolates (56 Escherichia coli isolates, 22 Klebsiella species isolates, 1 Proteus mirabilis isolate, and 7 Salmonella species isolates) exhibited broad-spectrum β-lactam resistance patterns. These organisms collectively produced three classes of β-lactamases, including class A extended-spectrum β-lactamases (n = 47), class C or AmpC β-lactamases (n = 36, including 4 isolates that produced both class A and class C enzymes), and class A or B carbapenem-hydrolyzing β-lactamases (n = 3). The proportion increased from 0.46% during the first 3 years to 1.84% during the last 3 years (relative risk [RR], 4.04; 95% confidence interval [CI], 2.28 to 7.42; P < 0.001). The increase was mainly due to the emergence of a plasmid-mediated blaCMY-2 β-lactamase, the incidence of which increased from 0.11% during the first 3 years to 0.96% during the last 3 years (RR, 9.11; 95% CI, 2.76 to 30.1; P = 0.001). Class A-type resistance increased slightly during the study period, from 0.35% during the first 3 years to 0.85% during the last 3 years (RR, 2.42; 95% CI, 1.15 to 5.07; P = 0.02). A Proteus mirabilis strain was documented to possess a novel blaDHA determinant. Of special concern, three carbapenemase-producing isolates were identified between 2003 and 2006. The infections caused by resistant isolates of the Enterobacteriaceae mainly affected hospitalized patients with underlying conditions; however, 19 (22%) episodes were of community onset in otherwise well children. The rate of resistance to broad-spectrum β-lactams among isolates of the Enterobacteriaceae is increasing in children in both hospital- and community-acquired settings, and the resistance is driven largely by plasmid-mediated AmpC β-lactamases. These data have important implications for empirical antimicrobial strategies targeting serious pediatric infections. Further study of this problem is warranted.

Epidemiologic Association Between FUT2 Secretor Status and Severe Rotavirus Gastroenteritis in Children in the United States

IMPORTANCE A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus. OBJECTIVE We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTS Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURES Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis. RESULTS One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations.

Discordant radiograph interpretation between emergency physicians and radiologists in a pediatric emergency department.

OBJECTIVES To describe the types of discrepancies in radiograph interpretation between emergency physicians and radiologists in a pediatric emergency department, and to determine the impact of discrepant interpretations on patient care. METHODS Prospective cohort study of discordant radiographs from the period beginning March 1, 1995 and ending March 31, 1996. During this period, 2083 radiographs were coded by the radiologist as concordant or discordant. Three hundred forty-nine were coded as discordant, and 324 were eligible for the study. Charts were reviewed for relevant physical examination findings and emergency department management. Discrepancies that affected patient care were deemed clinically significant. RESULTS Twenty-three (1.1%) of 2083 radiographs were interpreted differently by the emergency physician and the radiologist in a way that might have changed patient management. This represents 7% (23/324) of the radiographs originally coded by a radiologist as discrepant. The most common discrepancy was a patient with a normal chest examination and a radiograph interpreted as having an infiltrate by the emergency physician, but subsequently read as having no infiltrate by a radiologist (12/324). These patients may have received antibiotics unnecessarily. Two discrepant interpretations had the potential to have serious consequences to the patient if not identified. One patient with cardiomegaly and another patient with free air on abdominal radiograph were not noted by the emergency physician. CONCLUSIONS Emergency physicians would benefit from more rigorous interpretation of chest x-rays to avoid unnecessary treatment with antibiotics. Emergency physicians do a good job interpreting plain radiographs, but occasionally miss significant findings that could lead to adverse outcomes. The presence of radiologists to immediately read radiographs 24 hours a day could prevent missed findings, but, given the small number of significant misinterpretations, is unlikely to be cost effective.