Prevalence and Genetic Diversity of Adenovirus 40/41, Astrovirus, and Sapovirus in Children with Acute Gastroenteritis in Kansas City 2011-2016.

BACKGROUND: Most U.S. acute gastroenteritis (AGE) episodes in children are attributed to norovirus, whereas very little information is available on adenovirus 40/41 (AdV40/41), astrovirus or sapovirus. The New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based AGE surveillance in young children. METHODS: We tested and typed stool specimens collected between December 2011 to June 2016 from one NVSN site in Kansas City for the three viruses, and calculated hospitalization and emergency department (ED) detection rate. RESULTS: Of 3,205 collected specimens, 2,453 (76.5%) were from AGE patients (339 inpatients and 2,114 ED patients) and 752 (23.5%) were from healthy controls (HC). In AGE patients, astrovirus was detected in 94 (3.8%), sapovirus in 252 (10.3%) and AdV40/41 in 101 (4.5%) of 2249 patients. In HC, astrovirus was detected in 13 (1.7%) and sapovirus in 15 (2.0%) specimens. Astrovirus type 1 (37.7%) and genogroup I sapoviruses (59.3%) were most prevalent.Hospitalization rates were 5 (AdV40/41), 4 (astrovirus) and 8 (sapovirus) per 100,000 children <11 years old, whereas ED rates were 2.4 (AdV40/41), 1.9 (astrovirus) and 5.3 (sapovirus) per 1000 children <5 years old. CONCLUSIONS: Overall, AdV40/41, astrovirus, and sapovirus were detected in 18.6% of AGE in a large pediatric hospital in Kansas City.

Comparative in vitro antipseudomonal activity of ceftolozane/tazobactam against Pseudomonas aeruginosa isolates from children with cystic fibrosis.

This study evaluated the in vitro activity of Ceftolozane/tazobactam (C/T) vs 10 comparator agents against Pseudomonas aeruginosa isolates obtained from clinical respiratory samples from pediatric patients with cystic fibrosis at three hospitals during 2015 to 2020. Antimicrobial susceptibility testing was performed using microbroth dilution technique with custom prepared Sensititre® MIC plates. MICs were determined via Sensititre Vizion® system and results were interpreted using current CLSI and EUCAST (2022) breakpoint criteria. C/T was the most potent agent as compared with other antipseudomonal drugs against 291 isolates with MIC50 = 1 µg/mL and MIC90 = 2 µg/mL with percent susceptibility as 95.2%. C/T remained active against majority of ß-lactam non-susceptible isolates; percent susceptibility ranging from 61.2% to 80% including 65.9% ceftazidime non-susceptible isolates. C/T had high activity against P. aeruginosa from 3 geographically diverse pediatric medical centers. Study results suggest that C/T may be used as a potential therapeutic option for treating pediatric patients with CF.

Respiratory Virus Surveillance Among Children with Acute Respiratory Illnesses - New Vaccine Surveillance Network, United States, 2016-2021.

The New Vaccine Surveillance Network (NVSN) is a prospective, active, population-based surveillance platform that enrolls children with acute respiratory illnesses (ARIs) at seven pediatric medical centers. ARIs are caused by respiratory viruses including influenza virus, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human parainfluenza viruses (HPIVs), and most recently SARS-CoV-2 (the virus that causes COVID-19), which result in morbidity among infants and young children (1-6). NVSN estimates the incidence of pathogen-specific pediatric ARIs and collects clinical data (e.g., underlying medical conditions and vaccination status) to assess risk factors for severe disease and calculate influenza and COVID-19 vaccine effectiveness. Current NVSN inpatient (i.e., hospital) surveillance began in 2015, expanded to emergency departments (EDs) in 2016, and to outpatient clinics in 2018. This report describes demographic characteristics of enrolled children who received care in these settings, and yearly circulation of influenza, RSV, HMPV, HPIV1-3, adenovirus, human rhinovirus and enterovirus (RV/EV),* and SARS-CoV-2 during December 2016-August 2021. Among 90,085 eligible infants, children, and adolescents (children) aged <18 years† with ARI, 51,441 (57%) were enrolled, nearly 75% of whom were aged <5 years; 43% were hospitalized. Infants aged <1 year accounted for the largest proportion (38%) of those hospitalized. The most common pathogens detected were RV/EV and RSV. Before the emergence of SARS-CoV-2, detected respiratory viruses followed previously described seasonal trends, with annual peaks of influenza and RSV in late fall and winter (7,8). After the emergence of SARS-CoV-2 and implementation of associated pandemic nonpharmaceutical interventions and community mitigation measures, many respiratory viruses circulated at lower-than-expected levels during April 2020-May 2021. Beginning in summer 2021, NVSN detected higher than anticipated enrollment of hospitalized children as well as atypical interseasonal circulation of RSV. Further analyses of NVSN data and continued surveillance are vital in highlighting risk factors for severe disease and health disparities, measuring the effectiveness of vaccines and monoclonal antibody-based prophylactics, and guiding policies to protect young children from pathogens such as SARS-CoV-2, influenza, and RSV.

A multi-center study to determine genetic variations in the fusion gene of respiratory syncytial virus (RSV) from children <2 years of age in the U.S.

The fusion (F) protein of respiratory syncytial virus (RSV) is the major target of immunoprophylactic monoclonal antibodies (mAbs) and vaccines. Recently reported mutations in F gene antigenic sites can vary among RSV types A and B. To further understand mutations in RSV F proteins, we performed subtyping and F gene sequencing on 400 RSV-positive respiratory samples collected at four pediatric hospitals within the United States from children under 2 years old between 2018 and 2020. RSV B was predominant in 2018-2019 and RSV A in 2019-2020 (55.5% and 85.5% respectively). Compared to the reference sequence, all RSV B samples had at least one antigenic polymorphism with the most changes at sites AM14/V (100%) and Ø (93.3%) followed by II (5.8%), IV (3.9%), and p27 (2.9%). The most frequent mutations among RSV B for AM14/V site were in L172Q (100%), S173L (100%), and K191R (95.2%) while for Ø site they were in I206M (93.3%) and Q209R (93.3%). Conversely, polymorphisms were observed in only 15.3% of RSV A samples overall, specifically at antigenic sites p27 (5.9%), IV (3.0%), II (2.5%), AM14/V (2.0%), I (2.0%), and Ø (0.5%). Among RSV A cases, T122A at p27 (n = 10) and S276N at II (n = 3) were the most common substitution sites. S276N at site II was found in both RSV types. Although polymorphisms in F proteins of RSV B were more common than those in RSV A samples, changes in both subtypes were observed in key F antigenic sites which could potentially impact the efficacy of mAb therapies and vaccines.

Clinical Presentation and Severity of Adenovirus Detection Alone vs Adenovirus Co-detection With Other Respiratory Viruses in US Children With Acute Respiratory Illness from 2016 to 2018.

BACKGROUND: Human adenovirus (HAdV) is commonly associated with acute respiratory illnesses (ARI) in children and is also frequently co-detected with other viral pathogens. We compared clinical presentation and outcomes in young children with HAdV detected alone vs co-detected with other respiratory viruses. METHODS: We used data from a multicenter, prospective, viral surveillance study of children seen in the emergency department and inpatient pediatric settings at seven US sites. Children less than 18 years old with fever and/or respiratory symptoms were enrolled between 12/1/16 and 10/31/18 and tested by molecular methods for HAdV, human rhinovirus/enterovirus (HRV/EV), respiratory syncytial virus (RSV), parainfluenza (PIV, types 1-4), influenza (flu, types A-C), and human metapneumovirus (HMPV). Our primary measure of illness severity was hospitalization; among hospitalized children, secondary severity outcomes included oxygen support and length of stay (LOS). RESULTS: Of the 18,603 children enrolled, HAdV was detected in 1,136 (6.1%), among whom 646 (56.9%) had co-detection with at least one other respiratory virus. HRV/EV (n = 293, 45.3%) and RSV (n = 123, 19.0%) were the most frequent co-detections. Children with HRV/EV (aOR = 1.61; 95% CI = [1.11-2.34]), RSV (aOR = 4.48; 95% CI = [2.81-7.14]), HMPV (aOR = 3.39; 95% CI = [1.69-6.77]), or ≥ 2 co-detections (aOR = 1.95; 95% CI = [1.14-3.36]) had higher odds of hospitalization compared to children with HAdV alone. Among hospitalized children, HAdV co-detection with RSV or HMPV was each associated with higher odds of oxygen support, while co-detection with PIV or influenza viruses was each associated with higher mean LOS. CONCLUSIONS: HAdV co-detection with other respiratory viruses was associated with greater disease severity among children with ARI compared to HAdV detection alone.

A multicenter evaluation of viral bloodstream detections in children presenting to the Emergency Department with suspected systemic infection.

BACKGROUND: Fever is a common symptom in children presenting to the Emergency Department (ED). We aimed to describe the epidemiology of systemic viral infections and their predictive values for excluding serious bacterial infections (SBIs), including bacteremia, meningitis and urinary tract infections (UTIs) in children presenting to the ED with suspected systemic infections. METHODS: We enrolled children who presented to the ED with suspected systemic infections who had blood cultures obtained at seven healthcare facilities. Whole blood specimens were analyzed by an experimental multiplexed PCR test for 7 viruses. Demographic and laboratory results were abstracted. RESULTS: Of the 1114 subjects enrolled, 245 viruses were detected in 224 (20.1%) subjects. Bacteremia, meningitis and UTI frequency in viral bloodstream-positive patients was 1.3, 0 and 10.1% compared to 2.9, 1.3 and 9.7% in viral bloodstream-negative patients respectively. Although viral bloodstream detections had a high negative predictive value for bacteremia or meningitis (NPV = 98.7%), the frequency of UTIs among these subjects remained appreciable (9/89, 10.1%) (NPV = 89.9%). Screening urinalyses were positive for leukocyte esterase in 8/9 (88.9%) of these subjects, improving the ability to distinguish UTI. CONCLUSIONS: Viral bloodstream detections were common in children presenting to the ED with suspected systemic infections. Although overall frequencies of SBIs among subjects with and without viral bloodstream detections did not differ significantly, combining whole blood viral testing with urinalysis provided high NPV for excluding SBI.

Multiplex PCR Pathogen Detection in Acute Gastroenteritis Among Hospitalized US Children Compared With Healthy Controls During 2011-2016 in the Post-Rotavirus Vaccine Era.

BACKGROUND: Despite vaccine-induced decreases in US rotavirus (RV) disease, acute gastroenteritis (AGE) remains relatively common. We evaluated AGE pathogen distribution in hospitalized US children in the post-RV vaccine era. METHODS: From December 2011 to June 2016, the New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based surveillance in hospitalized children with AGE. We tested stools from 2 NVSN sites (Kansas City, Houston) with Luminex x-TAG Gastrointestinal Pathogen Panels (Luminex GPP) and analyzed selected signs and symptoms. RESULTS: For 660 pediatric AGE inpatients and 624 age-matched healthy controls (HCs), overall organism detection was 51.2% and 20.6%, respectively (P < .001). Among AGE subjects, GPP polymerase chain reaction detected >1 virus in 39% and >1 bacterium in 14% of specimens. Detection frequencies for AGE subjects vs HCs were norovirus (NoV) 18.5% vs 6.6%, RV 16.1% vs 9.8%, adenovirus 7.7% vs 1.4%, Shigella 4.8% vs 1.0%, Salmonella 3.1% vs 0.1%, and Clostridioides difficile in ≥2-year-olds 4.4% vs 2.4%. More co-detections occurred among AGE patients (37/660, 5.6%) than HCs (14/624, 2.2%; P = .0024). Per logistic regression analysis, ill contacts increased risk for NoV, RV, and Shigella (P < .001). More vomiting episodes occurred with NoV and RV, and more diarrheal episodes with Shigella and Salmonella. Modified Vesikari scores were highest for Shigella and lowest for C. difficile. CONCLUSIONS: NoV detection was most frequent; however, RV remained important in hospitalized AGE in the post-RV vaccine era. Continued active surveillance is important to document ongoing vaccine effects, pathogen emergence, and baseline disease burden for new vaccines.

Host Immune Response to Enterovirus and Parechovirus Systemic Infections in Children.

BACKGROUND: Enterovirus (EV) and parechovirus type A3 (PeV-A3) cause infections ranging from asymptomatic to life-threatening. Host immune responses in children, particularly innate responses to PeV-A3, remain largely unknown. The aim of this study was to determine aspects of the cytokine/chemokine responses to EV and PeV-A3 in cerebrospinal fluid (CSF) and plasma obtained from children with systemic/central nervous system infection. METHODS: A total of 74 salvaged CSF samples (27 with EV, 23 with PeV-A3, and 24 with neither EV nor PeV-A3) and 35 paired blood samples (10 with EV, 14 with PeV-A3, and 11 with neither) were studied. Concentrations of cytokines and chemokines were measured using a customized 21-plex MILLIPLEX MAP Human Cytokine/Chemokine Magnetic Bead Panel. Additionally, clinical characteristics data for all the patients were collected from electronic medical records to evaluate the potential association between the immune response and presentations. RESULTS: We demonstrate that EV and PeV-A3 infections induce different cytokine/chemokine immune responses in children. EV induces more robust responses in CSF with significantly elevated levels of fractalkine, interferon (IFN)-α2, IFN-γ, interleukin (IL)-1Rα, IL-4, IL-8, and tumor necrosis factor α; PeV-A3 induces less robust or absent responses in CSF but robust responses in plasma, with significantly higher concentrations of IFN-α2, IL-15, IL-1Rα, interferon-γ-inducible protein-10, and monocyte chemoattractant protein-1. CONCLUSIONS: High cytokine/chemokine concentrations in the plasma of PeV-A3 patients compared with EV patients could explain higher/more prolonged fever in PeV-A3 patients, whereas relatively low cytokine/chemokine concentrations in PeV-A3 CSF might explain the absence of CSF pleocytosis.

Frequency of asymptomatic and symptomatic respiratory virus detection in pediatric hematopoietic cell transplant patients.

Respiratory viral infections are common and can cause significant morbidity and mortality in pediatric patients undergoing hematopoietic cell transplantation (HCT). The prevalence of disease has been primarily identified from retrospective studies using standard-of-care specimens. The incidence of both asymptomatic respiratory viral detection and symptomatic respiratory viral detection in this high-risk population is not well described. We performed longitudinal, active, prospective surveillance in pediatric HCT patients. Subjects underwent weekly midturbinate swabs (MTSs) for the detection of 18 respiratory viruses and subtypes peri-HCT and 100 days post-HCT. Clinical data were obtained from the medical record. From September 2015 to February 2017, 24 children underwent 29 HCT, and 284 MTSs were collected. Forty-two (15%) specimens were virus-positive from 10 (42%) subjects. Specimens from children undergoing allogeneic HCT were more likely to have a virus detected (17% vs 8%, P = .04) compared with specimens from children undergoing autologous HCT. Sixteen (38%) detections were not associated with symptoms. Almost half (8/17) of the unique viral infections occurred during the HCT hospitalization after a negative specimen, suggesting nosocomial acquisition, and preceded detection from a clinical specimen. Rhinovirus, the most common virus detected, was the only virus detected in 33 (81%) virus-positive specimens; only 11 (33%) rhinovirus detections were asymptomatic. Asymptomatic detection of coronavirus and bocavirus occurred. Asymptomatic respiratory virus detection occurred in more than one-third of the children undergoing HCT. The acquisition of respiratory viruses during HCT hospitalization suggests nosocomial acquisition. Early detection of respiratory viruses during asymptomatic periods could have infection prevention and treatment implications.

Infectious Causes of Acute Gastroenteritis in US Children Undergoing Allogeneic Hematopoietic Cell Transplant: A Longitudinal, Multicenter Study.

BACKGROUND: Acute gastroenteritis (AGE) in hematopoietic cell transplant (HCT) patients causes significant morbidity and mortality. Data regarding the longitudinal assessment of infectious pathogens during symptomatic AGE and asymptomatic periods, particularly in children, are limited. We investigated the prevalence of AGE-associated infectious pathogens in children undergoing allogeneic HCT. METHODS: From March 2015 through May 2016, 31 pediatric patients at 4 US children's hospitals were enrolled and had stool collected weekly from pre-HCT through 100 days post-HCT for infectious AGE pathogens by molecular testing. Demographics, clinical symptoms, antimicrobials, vaccination history, and outcomes were manually abstracted from the medical record into a standardized case report form. RESULTS: We identified a pathogen in 18% (38/206) of samples, with many detections occurring during asymptomatic periods. Clostridioides difficile was the most commonly detected pathogen in 39% (15/38) of positive specimens, although only 20% (3/15) of C. difficile-positive specimens were obtained from children with diarrhea. Detection of sapovirus, in 21% (8/38) of pathogen-positive specimens, was commonly associated with AGE, with 87.5% of specimens obtained during symptomatic periods. Norovirus was not detected, and rotavirus was detected infrequently. Prolonged shedding of infectious pathogens was rare. CONCLUSIONS: This multicenter, prospective, longitudinal study suggests that the epidemiology of AGE pathogens identified from allogeneic HCT patients may be changing. Previously reported viruses, such as rotavirus and norovirus, may be less common due to widespread vaccination and institution of infection control precautions, and emerging viruses such as sapoviruses may be increasingly recognized due to the use of molecular diagnostics.

Evaluation of BacterioScan 216Dx in Comparison to Urinalysis as a Screening Tool for Diagnosis of Urinary Tract Infections in Children.

Urinalysis (UA) has routinely been used as a screening tool prior to urine culture set up. BacterioScan 216Dx is an FDA-cleared semiautomated system to detect bacterial growth in urine. The aim of this study was to evaluate 216Dx in comparison to UA for diagnosis of urinary tract infection (UTI) in children. Clean-catch, unpreserved urine samples from children aged <18 years were tested by 216Dx, and positive urine samples in media were processed for direct bacterial identification by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Sensitivity and specificity of 216Dx and urinalysis (UA) were determined against urine culture. Of 287 urine samples obtained from children (median age, 108 months), 44.0% and 56.0% were UA positive and negative, respectively, while 216Dx detected 27% and 73% as positive and negative, respectively. Compared to culture, the overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 216Dx versus UA were 92.1% versus 97.3%, 82.7% versus 63.8%, 44.8% versus 29.1%, and 98.6% versus 99.3%, respectively. Among 216Dx true-positive (TP) samples (n = 35), 77.0% were successfully identified directly from broth by MALDI-TOF. Among urine samples that were identified as contaminated by culture (n = 127; 44%), the 216Dx detected 93 (73.0%) as negative while UA detected 69 (54.0%) as negative. Although the sensitivities of 216Dx and UA are comparable, the specificity of 216Dx was higher than that of UA. The 216Dx can be used as an alternative/adjunct screening tool to UA to rule out urinary tract infection (UTI) in children. Compared to culture, the faster turnaround time (3 hours) of 216Dx has the potential to reduce unnecessary antibiotic use and improve patient management.

Viral Etiology of Acute Gastroenteritis in <2-Year-Old US Children in the Post-Rotavirus Vaccine Era.

BACKGROUND: The rotavirus disease burden has declined substantially since rotavirus vaccine was introduced in the United States in 2006. The aim of this study was to determine the viral etiology of acute gastroenteritis (AGE) in US children aged <2 years. METHODS: The New Vaccine Surveillance Network (NVSN) of geographically diverse US sites conducts active pediatric population-based surveillance in hospitals and emergency departments. Stool samples were collected from children aged <2 years with symptoms of AGE (n = 330) and age-matched healthy controls (HCs) (n = 272) between January and December 2012. Samples were tested by real-time reverse-transcriptase polymerase chain reaction assays {adenovirus (type 40 and 41), norovirus, parechovirus A, enterovirus, sapovirus, and astrovirus} and an enzyme immunoassay (rotavirus). All samples that tested positive were genotyped. RESULTS: Detection rates of pathogens in children with AGE versus those of HCs were, respectively, 23.0% versus 6.6% for norovirus (P < .01), 23.0% versus 16.0% for adenovirus (P = .08), 11.0% versus 16.0% for parechovirus A (P = .09), 11.0% versus 9.0% for enterovirus (P = .34), 7.0% versus 3.0% for sapovirus (P = .07), 3.0% versus 0.3% for astrovirus (P = .01), and 3.0% versus 0.4% for rotavirus (P = .01). A high prevalence of adenovirus was detected at 1 surveillance site (49.0% for children with AGE and 43.0% for HCs). Norovirus GII.4 New Orleans was the most frequently detected (33.0%) norovirus genotype. Codetection of >1 virus was more common in children with AGE (16.0%) than in HCs (10.0%) (P = .03). CONCLUSIONS: Norovirus, astrovirus, sapovirus, and rotavirus were detected significantly more in children with AGE than in HCs, and norovirus was the leading AGE-causing pathogen in US children aged <2 years during the year 2012.

Outcome of children with rhinovirus detection prior to allogeneic hematopoietic cell transplant.

Rhinoviruses are commonly detected in symptomatic and asymptomatic children prior to HCT. Unlike pre-HCT detection of other respiratory viruses, it is not known whether RV detection, with or without clinical symptoms, is associated with worse outcomes in children post-HCT. In a retrospective study of children undergoing allogeneic HCT from January 2009 to February 2015, 91 children underwent allogeneic HCT, and 62 children had RPP testing within 30 days pre-HCT. Fifty-six (90%) children had either no pathogen (n = 34, 55%) or single RV detection (n = 22, 35%), which was the most common pathogen identified. Compared with virus negative children, children with pre-HCT RV detection were not more likely to require ventilated support and did not have longer length of stay, higher mortality, or less days alive and out of the hospital within the first 100 days post-HCT. In a secondary analysis of all 56 patients with RPP testing and no pathogen or RV alone detected, the seven children with LRTI had less days alive and out of the hospital within the first 100 days post-HCT compared with the 49 children who were either asymptomatic or had URTI (10 vs 60 days, P = 0.002). In a bootstrapped regression model, presence of LRTI, not RV detection, was significantly associated with decreased days alive and out of the hospital within the first 100 days post-HCT. Thus, pre-HCT detection of RV, without associated LRTI, does not always warrant HCT delay.

Automated Real-Time Collection of Pathogen-Specific Diagnostic Data: Syndromic Infectious Disease Epidemiology.

BACKGROUND: Health care and public health professionals rely on accurate, real-time monitoring of infectious diseases for outbreak preparedness and response. Early detection of outbreaks is improved by systems that are comprehensive and specific with respect to the pathogen but are rapid in reporting the data. It has proven difficult to implement these requirements on a large scale while maintaining patient privacy. OBJECTIVE: The aim of this study was to demonstrate the automated export, aggregation, and analysis of infectious disease diagnostic test results from clinical laboratories across the United States in a manner that protects patient confidentiality. We hypothesized that such a system could aid in monitoring the seasonal occurrence of respiratory pathogens and may have advantages with regard to scope and ease of reporting compared with existing surveillance systems. METHODS: We describe a system, BioFire Syndromic Trends, for rapid disease reporting that is syndrome-based but pathogen-specific. Deidentified patient test results from the BioFire FilmArray multiplex molecular diagnostic system are sent directly to a cloud database. Summaries of these data are displayed in near real time on the Syndromic Trends public website. We studied this dataset for the prevalence, seasonality, and coinfections of the 20 respiratory pathogens detected in over 362,000 patient samples acquired as a standard-of-care testing over the last 4 years from 20 clinical laboratories in the United States. RESULTS: The majority of pathogens show influenza-like seasonality, rhinovirus has fall and spring peaks, and adenovirus and the bacterial pathogens show constant detection over the year. The dataset can also be considered in an ecological framework; the viruses and bacteria detected by this test are parasites of a host (the human patient). Interestingly, the rate of pathogen codetections, on average 7.94% (28,741/362,101), matches predictions based on the relative abundance of organisms present. CONCLUSIONS: Syndromic Trends preserves patient privacy by removing or obfuscating patient identifiers while still collecting much useful information about the bacterial and viral pathogens that they harbor. Test results are uploaded to the database within a few hours of completion compared with delays of up to 10 days for other diagnostic-based reporting systems. This work shows that the barriers to establishing epidemiology systems are no longer scientific and technical but rather administrative, involving questions of patient privacy and data ownership. We have demonstrated here that these barriers can be overcome. This first look at the resulting data stream suggests that Syndromic Trends will be able to provide high-resolution analysis of circulating respiratory pathogens and may aid in the detection of new outbreaks.

Comparison of three multiplex gastrointestinal platforms for the detection of gastroenteritis viruses.

BACKGROUND: Viruses are major etiological agents of childhood gastroenteritis. In recent years, several molecular platforms for the detection of viral enteric pathogens have become available. OBJECTIVE/STUDY DESIGN: We evaluated the performance of three multiplex platforms including Biofire's Gastrointestinal Panel (FilmArray), Luminex xTAG® Gastrointestinal Pathogen Panel (GPP), and the TaqMan Array Card (TAC) for the detection of five gastroenteritis viruses using a coded panel of 300 archived stool samples. RESULTS: The FilmArray detected a virus in 199 (96.1%) and the TAC in 172 (83.1%) of the 207 samples (187 samples positive for a single virus and 20 samples positive for more than one virus) whereas the GPP detected a virus in 100 (78.7%) of the 127 (97 positive for one virus and three positive for more than one virus) samples. Overall the clinical accuracy was highest for the FilmArray (98%) followed by TAC (97.2%) and GPP (96.9%). The sensitivity of the FilmArray, GPP and TAC platforms was highest for rotavirus (100%, 95.8%, and 89.6%, respectively) and lowest for adenovirus type 40/41 (97.4%, 57.9% and 68.4%). The specificity of the three platforms ranged from 95.6% (rotavirus) to 99.6% (norovirus/sapovirus) for the FilmArray, 99.6% (norovirus) to 100% (rotavirus/adenovirus) for GPP, and 98.9% (astrovirus) to 100% (rotavirus/sapovirus) for TAC. CONCLUSION: The FilmArray demonstrated the best analytical performance followed by TAC. In recent years, the availability of multi-enteric molecular testing platforms has increased significantly and our data highlight the strengths and weaknesses of these platforms.

Reducing Overutilization of Testing for Clostridium difficile Infection in a Pediatric Hospital System: A Quality Improvement Initiative.

OBJECTIVES: Study objectives included addressing overuse of Clostridium difficile laboratory testing by decreasing submission rates of nondiarrheal stool specimens and specimens from children ≤12 months of age and determining resultant patient and laboratory cost savings associated with decreased testing. METHODS: A multifaceted initiative was developed, and components included multiple provider education methods, computerized order entry modifications, and automatic declination from laboratory on testing stool specimens of nondiarrheal consistency and from children ≤12 months old. A run chart, demonstrating numbers of nondiarrheal plus infant stool specimens submitted over time, was developed to analyze the initiative's impact on clinicians' test-ordering practices. A p-chart was generated to evaluate the percentage of these submitted specimens tested biweekly over a 12-month period. Cost savings for patients and the laboratory were assessed at the study period's conclusion. RESULTS: Run chart analysis revealed an initial shift after the interventions, suggesting a temporary decrease in testing submission; however, no sustained differences in numbers of specimens submitted biweekly were observed over time. On the p-chart, the mean percentage of specimens tested before the intervention was 100%. After the intervention, the average percentage of specimens tested dropped to 53.8%. Resultant laboratory cost savings totaled nearly $3600, and patient savings on testing charges were ∼$32 000. CONCLUSIONS: Automatic laboratory declination of nondiarrheal stools submitted for CDI testing resulted in a sustained decrease in the number of specimens tested, resulting in significant laboratory and patient cost savings. Despite multiple educational efforts, no sustained changes in physician ordering practices were observed.

Prevalence of 3 sexually transmitted infections in a pediatric emergency department.

OBJECTIVE: This study aimed to determine the prevalence of Chlamydia trachomatis, Neisseria gonorrheae, and Trichomonas vaginalis and to describe factors associated with sexually transmitted infection (STI) in a pediatric emergency department (ED). METHODS: Adolescents aged 14 to 19 years presenting to a Midwestern pediatric ED were asked to provide urine for STI testing and complete a survey about previous sexual activity (PSA), high-risk behaviors, demographics, and visit reason (reproductive: genitourinary complaints, abdominal pain, or a female with vomiting). Comparisons between subgroups were analyzed using Χ test. RESULTS: Among 200 subjects (64% of approached), mean age was 15.6 years; 63% were female. Eleven subjects (6%; 95% confidence interval, 2.3-8.7) tested positive for 1 or more STIs: 10 for C. trachomatis (one denied PSA), 3 for T. vaginalis (all coinfected with C. trachomatis), and 1 for N. gonorrheae. Half reported PSA; of these, 71% reported 1 or more high-risk behaviors, most commonly first sex before the age of 15 years (51%) and no condom at last sex (42%). Among those with PSA and nonreproductive visit (n = 73), 11.0% had 1 or more STIs (95% confidence interval, 3.4-18.1). Two factors were associated with greater likelihood of positive STI test result, namely, reporting PSA versus no PSA (10% vs 1%, P = 0.005) and last sex within 1 month or less versus more than 1 month (20% vs 0%, P = 0.001). In this sample, none of the following characteristics were associated with STI: insurance, race, high-risk behaviors, age, or ED visit reason. CONCLUSIONS: Approximately 1 in 10 sexually active adolescent ED patients without reproductive complaints had 1 or more STIs. This suggests the need for strategies to increase STI testing for this population.

Utility of a focused vancomycin-resistant enterococci screening protocol to identify colonization in hospitalized children.

Screening for vancomycin-resistant enterococci (VRE) is controversial, and disagreement exists on policy implementation. This study investigated the likelihood of a positive test using 1, 2, or 3 rectal screenings for VRE colonization. In this descriptive study of positive VRE screening cultures, a total of 1211 VRE screens identified 41 positive results. The mean age of these positive patients was 5.7 years. Thirty-nine of the 41 had a chronic illness, and only 2 were healthy. Diagnoses included pulmonary disease in 11 patients and chronic gastrointestinal abnormality in 7. Six patients had been born preterm, and 12 had been treated in a neonatal intensive care unit within the previous 6 months. Thirty-six of the 41 positive results were identified on the first screen. The likelihood of subsequently having a positive screen after a negative screen was 0.43% (95% confidence interval, 0.15%-1.02%). The cost of cultures plus isolation was $50,000 for the study period. Our data show that the likelihood of detecting a positive VRE culture after an initial negative was low, particularly in otherwise healthy children.

Demographics and microbiology of otorrhea through patent tubes failing ototopical and/or oral antibiotic therapy.

OBJECTIVES: Posttympanostomy tube otorrhea (PTTO) results in significant health care cost and decreased satisfaction with care. The authors reviewed PTTO failing initial ototopical and/or oral antibiotic therapy and microbiology/susceptibility data from cultures. STUDY DESIGN: Case series with chart review. SETTING: A community university satellite ambulatory clinic and the outpatient clinic of a children's hospital. METHODS: Review of 202 patients with 228 discrete episodes of culture-positive otorrhea from January 2004 to January 2009. RESULTS: PTTO occurred an average of 13 months after tube placement. Median otorrhea duration was 21 days (mean, 42 days). A mean of 1.6 visits (range, 1-6) to the pediatric otolaryngology office was required for PTTO resolution. Ototopical therapy was reported used in 198 of 228 (87%) episodes of otorrhea prior to pediatric otolaryngology visit. Nearly 50% of patients were prescribed at least 1 or more courses of systemic antibiotics. Staphylococcus aureus accounted for 52% of the organisms cultured, with 57% methicillin-resistant S aureus (MRSA). S aureus resistance to clindamycin was high (49%) and resistance to levofloxacin was low (1.8%). MRSA was 68% clindamycin resistant, much higher than both ours and the children's hospital's clindamycin resistance rate of MRSA cultured from all other body sites. CONCLUSIONS: PTTO that presents as having failed ototopical and/or oral antibiotics most commonly consists of S aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. MRSA is highly prevalent in this population. It is not necessary to culture PTTO that presents to an otolaryngology office, as resistance to levofloxacin was only 1.8%. It is unclear why the same fluoroquinolone ototopical therapy that failed initially is often successful in treating PTTO after otolaryngologist visit.

Molecular epidemiology and clinical presentation of human adenovirus infections in Kansas City children.

BACKGROUND: A significant increase in adenovirus detection among patients at the Children's Mercy Hospital, Kansas City was observed between June 2007 and January 2008. OBJECTIVE: To molecularly characterize the human adenoviruses and describe their association with clinical illness in children. STUDY DESIGN: One hundred adenovirus-positive specimens from 79 children were typed by hexon gene sequence typing method. Restriction enzyme analysis (REA) was performed on isolates of HAdV-3, -7 and -14 to identify genomic variants. Medical records were reviewed to understand the clinical illnesses associated with adenovirus serotypes and genome types. RESULTS: The most prevalent HAdV serotypes were HAdV-3 (37%), HAdV-7 (25%), HAdV-1 (16%), HAdV-2 (8%). HAdV infection was common in children ≤3 years of age (71%) versus children >3 years (29%). Majority of the HAdV-infected children were hospitalized (78%); 22/79 (28%) stayed >3 days and 8/79 (10%) required intensive care unit stay. Hospitalization rates for HAdV-3 (36%) and HAdV-7 (25%) were comparable. REA data indicated that HAdV-3a2 was the predominant HAdV-3 genome type. Two novel genomic variants of HAdV-3 exhibiting unique BglII or BstEII profiles were identified in isolates from patients with bronchiolitis. All HAdV-7 and -14 isolates were identified as corresponding to genome types 7d2 and 14p1, respectively. CONCLUSIONS: In Kansas City, we noticed an increase in the incidence of HAdV-7 (25%; n=24/98) infections compared to the previous two years (6%; n=6/107). Two new genomic variants of HAdV-3 appear to have emerged in our area and seem to be associated with lower respiratory tract infections in children.