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BackgroundChildren are an important population to test for COVID-19 infection, particularly because they may shed the virus without displaying symptoms. Testing children for COVID-19 via sensitive molecular methods is important, although collecting nasopharyngeal (NP) specimens can be challenging. A less invasive mode of specimen collection that yields test results comparable to those from NP specimens would be beneficial to simplify sample collection.MethodsTo demonstrate that saliva is a suitable specimen for collection from children, the clinical usability/acceptability and the analytic performance of saliva were compared to NP specimens suspended in viral transport medium. Four different FDA EUA-approved real-time RT-PCR assays and one EUA approved saliva collection device were investigated.ResultsThe study population included 526 patients between the ages of 3 and 61 years, 461 (88%) were ConclusionsOf the four FDA EUA-approved SARS-CoV-2 PCR assays studied, we found the AllPlex assay to be best suited for testing saliva specimens collected from children 5 years of age or older. The sensitivity of viral detection was equivalent to NP specimens when saliva specimens were mixed with the saliva stabilizer.

Objectives:To describe the incidence of seasonal respiratory viral infections (s-RVIs) before and during the coronavirus disease 2019 (COVID-19) pandemic and to compare virus-specific patient outcomes in pediatric patients.Design:A retrospective cross-sectional study including patient admissions to the Children’s National Hospital between October 1, 2015, and December 31, 2020.Results:Among 12,451 patient admissions between March 15 and December 31, 2020 (cohort 1), 8,162 (66%) were tested for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and 249 (2.0%) were positive. Among 10,986 patient admissions between April 1 and December 31, 2020 (cohort 2), 844 (8%) were tested for s-RV upon admission and 160 were positive. Thus, 1.5% of patient admissions were associated with laboratory-confirmed s-RVIs. Among the 49,901 patient admissions during a viral season between October 1, 2015, and March 31, 2020 (cohort 3), 7,539 (15%) were tested for s-RV upon admission and 4,531 were positive; thus, 9.0% of patient admissions were associated with laboratory-confirmed s-RVIs. hHRV/rENT was the most detected virus, but the detection rate decreased substantially (31% vs 18%; P < .001) during the COVID-19 pandemic. No patients had RSV, influenza, hMPV, hPIV, or hCoV detected upon admission after April 21, 2020. The 3 patient cohorts had no statistically significant difference in the percentage of ICU admissions (10.8% vs 15.0% vs 14.2%; P > .05) or death at discharge (0.8% vs 0.6% vs 0.5%; P > .05).Conclusions:Compared to COVID-19, s-RVI cases were associated with a higher proportion of inpatient admissions but were similar in ICU admission and death rates in hospitalized pediatric patients. Public health interventions for preventing COVID-19 were highly effective in preventing pediatrics s-RVIs.

The evolution of SARS-CoV2 virus has led to the emergence of variants of concern (VOC). Children, particularly

The SARS-CoV-2 virus has emerged as a global pandemic, severely impacting everyday life. Significant resources have been dedicated towards profiling the viral genome in the adult population. We present an analysis of viral genomes acquired from pediatric patients presenting to Children’s National Hospital in Washington D.C, including 24 with primary SARS CoV2 infection and 3 with Multisystem Inflammatory Syndrome in Children (MIS-C) undergoing treatment at our facility. Viral genome analysis using next generation sequencing indicated that approximately 81% of the analyzed strains were of the GH clade, 7% of the cases belonged to the GR clade, and 12% of the cases belonged to S, V, or G clades. One sample, acquired from a neonatal patient, presented with the highest viral RNA load of all patients evaluated at our center. Viral sequencing of this sample identified a SARS-CoV-2 spike variant, S:N679S. Analysis of data deposited in the GISAID global database of viral sequences shows the S:N679S variant is present in eight other sequenced samples within the US mid-Atlantic region. The similarity of the regional sequences suggests transmission and persistence of the SARS-CoV-2 variant within the Capitol region, raising the importance of increasing the frequency of SARS-CoV-2 genomic surveillance.IMPORTANCEA variant in the SARS-CoV-2 spike protein was identified in a febrile neonate who was hospitalized with COVID-19. This patient exhibited the highest viral RNA load of any COVID-19 patient tested at our center. Viral sequencing identified a spike protein variant, S:N679S, which is proximal to the cleavage site at residue 681. The SARS-CoV-2 surface spike is a protein trimer (three subunits) which serves as the key target for antibody therapies and vaccine development. Study of viral sequences from the GISAID database revealed eight related sequences from the US mid-Atlantic region. The identification of this variant in a very young patient, its critical location in the spike polyprotein, and the evidence that it has been detected in other patients in our region underscores the need for increased viral sequencing to monitor variant prevalence and emergence, which may have a direct impact on recommended public health measures and vaccination strategies.

This cohort study compares the clinical features of coronavirus disease 2019 (COVID-19) with those of influenza A and B in US children., Key Points Question What are the similarities and differences in clinical features between coronavirus disease 2019 (COVID-19) and seasonal influenza in US children? Findings In this cohort study of 315 children with COVID-19 and 1402 children with seasonal influenza, there were no statistically significant differences in the rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use between the 2 groups. More patients with COVID-19 than with seasonal influenza reported fever, diarrhea or vomiting, headache, body ache, or chest pain at the time of diagnosis. Meaning The findings suggest that prevention of both COVID-19 and seasonal influenza in US children is prudent and urgent for the well-being of this population., Importance Compared with seasonal influenza, the clinical features and epidemiologic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus 2019 (COVID-19) in US children remain largely unknown. Objective To describe the similarities and differences in clinical features between COVID-19 and seasonal influenza in US children. Design, Setting, and Participants This retrospective cohort study included children who were diagnosed with laboratory-confirmed COVID-19 between March 25 and May 15, 2020, and children diagnosed with seasonal influenza between October 1, 2019, and June 6, 2020, at Children’s National Hospital in the District of Columbia. Exposures COVID-19 or influenza A or B. Main Outcomes and Measures Rates of hospitalization, admission to the intensive care unit, and mechanical ventilator use and the association between underlying medical conditions, clinical symptoms, and COVID-19 vs seasonal influenza. Results The study included 315 patients diagnosed with COVID-19 (164 [52%] male; median age, 8.3 years [range, 0.03-35.6 years]) and 1402 patients diagnosed with seasonal influenza (743 [53%] male; median age, 3.9 years [range, 0.04-40.4 years]). Patients with COVID-19 and those with seasonal influenza had a similar hospitalization rate (54 [17%] vs 291 [21%], P = .15), intensive care unit admission rate (18 [6%] vs 98 [7%], P = .42), and use of mechanical ventilators (10 [3%] vs 27 [2%], P = .17). More patients hospitalized with COVID-19 than with seasonal influenza reported fever (41 [76%] vs 159 [55%], P = .005), diarrhea or vomiting (14 [26%] vs 36 [12%], P = .01), headache (6 [11%] vs 9 [3%], P = .01), body ache or myalgia (12 [22%] vs 20 [7%], P = .001), and chest pain (6 [11%] vs 9 [3%], P = .01). Differences between patients hospitalized with COVID-19 vs influenza who reported cough (24 [48%] vs 90 [31%], P = .05) and shortness of breath (16 [30%] vs 59 [20%], P = .13) were not statistically significant. Conclusions and Relevance In this cohort study of US children with COVID-19 or seasonal influenza, there was no difference in hospitalization rates, intensive care unit admission rates, and mechanical ventilator use between the 2 groups. More patients hospitalized with COVID-19 than with seasonal influenza reported clinical symptoms at the time of diagnosis.

ObjectivesTo improve understanding of transition from viral infection to viral clearance, and antibody response in pediatric patients with SARS-CoV-2 infection.Study designThis retrospective analysis of children tested for SARS-CoV-2 by RT-PCR and IgG antibody at a quaternary-care, free-standing pediatric hospital between March 13th, 2020 to June 21st, 2020 included 6369 patients who underwent PCR testing and 215 patients who underwent antibody testing. During the initial study period, testing focused primarily on symptomatic children; the later study period included asymptomatic patients who underwent testing as preadmission or preprocedural screening. We report the proportion of positive and negative tests, time to viral clearance, and time to seropositivity.ResultsThe rate of positivity varied over time due to viral circulation in the community and transition from targeted testing of symptomatic patients to more universal screening of hospitalized patients. Median duration of viral shedding (RT-PCR positivity) was 19.5 days and RT-PCR negativity from positivity was 25 days. Of note, patients aged 6 to 15 years demonstrated a longer period of RT-PCR negativity from positivity, compared to patients aged 16 to 22 years (median=32 versus 18 days, p=0.015). Median time to seropositivity from RT-PCR positivity was 18 days while median time to reach adequate levels of neutralizing antibodies (defined as equivalent to 160 titer) was 36 days.ConclusionsThe majority of patients demonstrated a prolonged period of viral shedding after infection with SARS CoV-2. Whether this correlates with persistent infectivity is unknown. Only 17 of 33 patients demonstrated neutralizing antibodies, suggesting that some patients may not mount significant immune responses to infection. It remains unknown if IgG antibody production correlates with immunity and how long measurable antibodies persist and protect against future infection.

Worldwide, there have been few reports of β-lactamases causing penicillin resistance in Neisseria meningitidis. The first known case of disease in the United States due to a β-lactamase-producing, ciprofloxacin-resistant N. meningitidis was recently identified. This has potential implications on standard laboratory testing and empiric management of meningococcal disease.

Background Probiotics are used frequently in the pediatric population for treatment of diarrhea and promotion of gastrointestinal health. Lactobacillus is the most commonly used bacterial genus in probiotic formulations. Lactobacillus spp. has been a reported cause of bacteremia, particularly in immunocompromised populations and individuals with impaired gut integrity. To assess the risks and benefits of inpatient probiotic use in a pediatric tertiary care center, we aimed to identify the occurrence of Lactobacillus bacteremia among hospitalized patients and its association with probiotic use over an eleven-year period. Methods Cases of Lactobacillus bacteremia were identified through a search of positive blood culture reports from January 1st, 2010 through December 31st, 2020. The clinical chart for each case was independently reviewed for the following risk factors: documented probiotic uses, presence of a central venous catheter, immunocompromising condition or immunosuppressive agent, neutropenia, impaired intestinal function and age below 3 months. Additionally, we reviewed the clinical presentation including presence of fever, need for intensive care and gastrointestinal symptoms. Total inpatient probiotic administration was assessed over the same time period. Results Eight cases of Lactobacillus bacteremia were identified in inpatients during the study time period. Two cases had received probiotics in the hospital and a third case had documented outpatient administration of probiotics prior to development of bacteremia. The remaining five cases had no documented probiotic use. All 8 cases were febrile at the time of bacteremia. No patients required blood pressure support medications. Five cases had underlying impaired intestinal function. One case was in an oncology patient and there were no cases in solid organ or bone marrow transplant patients. Two cases, including the oncology patient and one patient with impaired intestinal function, were neutropenic at the time of bacteremia. All but one case, had a central line in place. All cases were treated with antibiotics and had resolution of bacteremia and associated symptoms. Probiotics were administered to 4,478 inpatients during the study period. Conclusions Lactobacillus bacteremia is uncommon and occurred in under 0.2% of patients who received probiotics during an inpatient admission. Nevertheless, all eight observed cases were symptomatic and received antibiotic therapy. Additionally, cases were most commonly seen in individuals with underlying impaired intestinal function. These considerations must be weighed in decisions regarding the risks and benefits of probiotic administration in the hospital.

Objectives To improve understanding of transition from viral infection to viral clearance, and antibody response in pediatric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Study design This retrospective analysis of children tested for SARS-CoV-2 by reverse transcription (RT) polymerase chain reaction (PCR) and immunoglobulin G antibody at a quaternary-care, free-standing pediatric hospital between March 13, 2020, and June 21, 2020, included 6369 patients who underwent PCR testing and 215 patients who underwent antibody testing. During the initial study period, testing focused primarily on symptomatic children; the later study period included asymptomatic patients who underwent testing as preadmission or preprocedural screening. We report the proportion of positive and negative tests, time to viral clearance, and time to seropositivity. Results The rate of positivity varied over time due to viral circulation in the community and transition from targeted testing of symptomatic patients to more universal screening of hospitalized patients. Median duration of viral shedding (RT-PCR positivity) was 19.5 days and time from RT-PCR positivity to negativity was 25 days. Of note, patients aged 6 through 15 years demonstrated a longer time of RT-PCR positivity to negativity, compared with patients aged 16 through 22 years (median 32 vs 18 days, P = .015). Median time to seropositivity, by chemiluminescent testing, from RT-PCR positivity was 18 days, whereas median time to reach adequate levels of neutralizing antibodies (defined as comparable with 160 titer by plaque reduction neutralization testing) was 36 days. Conclusions The majority of patients demonstrated a prolonged period of viral shedding after infection with SARS CoV-2. It is unknown whether this correlates with persistent infectivity. Only 17 of 33 patients demonstrated adequate neutralizing antibodies during the time frame of specimen collection. It remains unknown whether immunoglobulin G antibody against spike structured proteins correlates with immunity, and how long antibodies and potential protection persist.

Background Children and young adults were initially reported as largely spared from severe complications of SARS-CoV-2 infection, but the impact to this population has been significant. Methods This observational retrospective cohort study includes 420 symptomatic children and young adults with lab confirmed SARS-CoV-2 infection treated between March 15 and June 16, 2020 at Children’s National Hospital in Washington DC. We identified and compared cohorts of non-hospitalized (N=324) and hospitalized (N=96) patients, including non-critically ill (N=64) and critically ill hospitalized (N=32) patients. Clinical and demographic data were extracted from medical records Results Of 420 SARS-CoV-2-infected symptomatic patients, 23% required hospitalization, of which 67% were non-critically ill and 33% were critically ill. All age groups were represented in the symptomatic cohort, with a median age of 8.6 years. Patients > 15 years of age represented 44% of critical care admissions. Males and females were equally represented in all cohorts. Underlying medical conditions were present in 36%, but more common in hospitalized (59 %) and critically ill (66 %) patients. The most frequent underlying diagnosis overall was asthma (16 %), but also included neurologic (6 %), diabetes (3 %), obesity (3 %), cardiac (3 %), hematologic (3 %) and oncologic (1 %) conditions. The majority (66 %) of SARS-CoV-2 infected patients presented with respiratory symptoms with or without fever. Other symptoms were also present, including diarrhea/vomiting (21 %), myalgia (11 %), chest pain (8 %) and loss of sense of smell or taste (7%). Hospitalized patients required varying levels of respiratory support, including mechanical ventilation, BiPAP, RAM cannula and HFNC. Additional presentations included diabetic hyperglycemia, sickle cell vaso-occlusive crisis, vascular complications, and multisystem inflammation. Treatment included remdesivir, convalescent plasma, tocilizumab and other therapies. Conclusion Although children/young adults have been less affected than elderly adults, the impact of SARS-CoV2 on this population has been significant in Washington DC and informs other regions anticipating their surge. Disclosures Andrea Hahn, MD, MS, Johnson and Johnson (Consultant)

Background Blood cultures have high sensitivity to detect bacteremia in septic neonates when >=1 ml of blood is collected. Neonatologists often cite low confidence in microbiologic sampling as rationale for continuing antibiotics without a focus of infection despite negative blood cultures, resulting in prolonged antimicrobial therapy. We aim to describe the blood culture sample volumes in NICU patients, to identify factors associated with sample volumes < 1ml, and to compare the sample volumes of patients treated for culture-negative sepsis with those with bloodstream infections and those treated for a ≤72-hour sepsis rule-out Methods Data from this observational cohort study were collected retrospectively and prospectively from NICU patients with blood cultures obtained from September 2018 to February 2019. Clinical data were collected through chart review. All inoculated culture bottles were weighed for volume calculation. We determined the association of age, weight, sample source, and time of collection with volume < 1mL. Continuous variables were analyzed using Wilcoxon-Mann-Whitney, and categorical variables using chi-squared test. For aim 3, the volumes of the groups were compared using analysis of variance. Results A total of 310 blood cultures were identified, corresponding to 159 patients. Of these, 49 (16%) were positive. Among the negative blood cultures, 86% were collected in patients who subsequently received antibiotics (Figure 1). Median inoculated volume was 0.6 ml (IQR: 0.1-2.4). Weight and age at time of culture collection, source of sample, and time of collection were not significantly associated with the inoculation of < 1ml of blood. Median volume of blood was 0.6ml (0.3-0.6) for sepsis rule-out, 0.6ml (0.2-0.6) for bloodstream infection, and 0.6ml (0.6-1.4) for culture-negative sepsis. No difference was found among the three groups (p=0.54) Figure 1. Classification of blood cultures identified during study period Conclusion The blood volume collected for cultures in the NICU is lower than recommended. Clinical and environmental characteristics are not significantly associated with the inoculated volume. The volume of blood sampled does not differ in patients with culture-negative sepsis, bloodstream infection and sepsis rule-out, and should not be a justification for longer duration of antibiotic therapy Disclosures All Authors: No reported disclosures

BACKGROUND Bacteremia caused by members of the Enterobacteriaceae can be life threatening. Appropriate antimicrobial therapy is critical to reducing morbidity and mortality. METHODS This retrospective cohort study (2008-2011) was conducted in children and young adults (

Background Cystic fibrosis (CF) is an autosomal recessive disease characterized by recurrent lung infections. Studies of the lung microbiome have shown an association between decreasing diversity and progressive disease. 454 pyrosequencing has frequently been used to study the lung microbiome in CF, but will no longer be supported. We sought to identify the benefits and drawbacks of using two state-of-the-art next generation sequencing (NGS) platforms, MiSeq and PacBio RSII, to characterize the CF lung microbiome. Each has its advantages and limitations. Methods Twelve samples of extracted bacterial DNA were sequenced on both MiSeq and PacBio NGS platforms. DNA was amplified for the V4 region of the 16S rRNA gene and libraries were sequenced on the MiSeq sequencing platform, while the full 16S rRNA gene was sequenced on the PacBio RSII sequencing platform. Raw FASTQ files generated by the MiSeq and PacBio platforms were processed in mothur v1.35.1. Results There was extreme discordance in alpha-diversity of the CF lung microbiome when using the two platforms. Because of its depth of coverage, sequencing of the 16S rRNA V4 gene region using MiSeq allowed for the observation of many more operational taxonomic units (OTUs) and higher Chao1 and Shannon indices than the PacBio RSII. Interestingly, several patients in our cohort had Escherichia , an unusual pathogen in CF. Also, likely because of its coverage of the complete 16S rRNA gene, only PacBio RSII was able to identify Burkholderia , an important CF pathogen. Conclusion When comparing microbiome diversity in clinical samples from CF patients using 16S sequences, MiSeq and PacBio NGS platforms may generate different results in microbial community composition and structure. It may be necessary to use different platforms when trying to correctly identify dominant pathogens versus measuring alpha-diversity estimates, and it would be important to use the same platform for comparisons to minimize errors in interpretation.

Adenovirus (AdV) infections are a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). To evaluate the use of molecular AdV testing in HSCT at our institution and identify risk factors for AdV viremia and disease, we performed a retrospective cohort study of all HSCT recipients who had undergone AdV polymerase chain reaction testing over a 2-year period. Two cohorts were identified: cohort 1, comprising patients testing positive for AdV (n = 7) and cohort 2, comprising patients testing negative (n = 36). Overall patient characteristics were not statistically significantly different between the 2 cohorts. A comparison of cohort 1 and cohort 2 identified the following medication exposures as risk factors influencing AdV status: preparatory regimens using fludarabine (relative risk [RR], 8.73; 95% confidence interval [CI], 1.18-64.27; P = .006), melphalan (RR, 3.47; 95% CI, 0.76-15.94: P = .08), and/or cyclophosphamide (RR, 0.18; 95% CI, 0.02-1.4; P = .05), and GVHD prophylaxis with methylprednisone (RR, 3.73; 95% CI, 1.01-13.9; P = .04). AdV-positive patients had higher grades of GVHD and higher rates of GVHD of the gastrointestinal tract (RR, 4; 95% CI, 1.18-13.5; P = .03) compared with AdV-negative patients. Four of the 7 AdV-positive patients had concomitant clinical manifestations of disease, including pneumonia, diarrhea, and/or disseminated disease. Clinical outcomes in symptomatic patients included resolution of disease in 2 patients and death in 2 patients. All 7 AdV-positive patients received antiviral therapy, including 1 patient with severe disseminated disease that resolved after administration of liposomal cidofovir. Our study at a large pediatric HSCT center provides important preliminary data for the development of a prospective trial destined to identify specific HCST patient subpopulations that might benefit most from molecular screening and early preemptive therapy.

Background. Imported malaria remains a public health concern in the United States, but the health impact on children and the financial costs to society have not been well defined. Methods. Inpatient and outpatient malaria cases diagnosed at Children's National Medical Center (CNMC) in Washington, DC over an 8-year period are retrospectively reviewed. Cases are mapped against Census Bureau population data. These observations are compared with the national burden of pediatric malaria, including both disease severity and cost, by reviewing inpatient malaria cases in the Pediatric Health Information System (PHIS), January 2003 to June 2008. Results. At CNMC, malaria most commonly affects children who traveled to West Africa to visit friends and relatives. Poor adherence to prophylaxis and self-treatment with antimalarial medications were commonly identified. Mapping demonstrates case clustering in communities with large sub-Saharan African populations. The cumulative incidence (CI) of malaria at CNMC of 9.0 per 10,000 admissions is 7.6 times the national average. The CI of malaria at PHIS hospitals is 1.2 per 10,000 admissions with an average cost of $17,519. Conclusions. Malaria is a preventable disease for which the risk to life and costs of treatment are significant. Patterns of risk can be used by health planners to target prevention strategies at the community level. In regions with a high density of immigrants, particularly from sub-Saharan Africa, physicians must be aware of the risk, understand recommended prophylaxis and treatment regimens, and advocate for their appropriate use in the community.

Background Preventing methicillin-resistant Staphylococcus aureus (MRSA) transmission in health care facilities where MRSA is endemic is challenging yet critical. Objective We sought to determine the effectiveness of 2 bundles of interventions for preventing MRSA transmission in a neonatal intensive care unit (NICU). Methods This retrospective cohort study included infants admitted to our NICU between September 1, 2004, and March 31, 2009. Following a MRSA outbreak between September 2004 and September 2005, preventing ongoing MRSA transmission remained a challenge. In July 2006, bundle-I, including culture-based active surveillance, preemptive contact precaution for up to 72 hours for new admissions, and cohorting assignment of direct caregivers was introduced for eradicating MRSA transmission. Bundle-II began in April 2007 and included bundle-1 measures except that the real-time polymerase chain reaction test replaced culture for the detection of MRSA. Results This study identified 218 infants who developed MRSA infection or colonization and 151 instances of MRSA transmission during the study period. After instituting bundle-II, the transmission rate declined from 2.9 to 2.1 per 1000 patient-days-at-risk (incidence rate ratio, 1.4; 95% confidence interval: 0.9-2.2), and hospital-acquired MRSA infections declined from 1.3 to 0.5 per 1000 patient-days-at-risk (incidence rate ratio, 2.5; 95% confidence interval: 1.1-5.8). Conclusion Despite an increasing incidence of MRSA in community settings, preventing MRSA transmission within a NICU is achievable through implementation of optimal intervention strategies.

Objective.The rising incidence and mortality of methicillin-resistant Staphylococcus aureus (MRSA) colonization or infection in children has become a great concern. This study aimed to determine the clinical and economic impact of MRSA colonization or infection on infants and to measure excess mortality, length of stay, and hospital charges attributable to MRSA.Design.This is a retrospective cohort study.Setting and Patients.The study included infants admitted to a level III-IV neonatal intensive care unit from September 1, 2004, through March 31, 2008.Methods.A time-dependent proportional hazard model was used to analyze the association between MRSA colonization or infection and mortality. The relationships between MRSA colonization or infection and length of stay and between MRSA colonization or infection and hospital charges were assessed using a matched cohort study design.Results.Of 2,280 infants, 191 (8.4%) had MRSA colonization or infection. Of 132 MRSA isolates with antibiotic susceptibility results, 106 were resistant to clindamycin and/or trimethoprim-sulfamethoxazole, thus representing a noncommunity phenotype. The mortality rate was 17.8% for patients with MRSA colonization or infection and 11.5% for control subjects. Neither MRSA colonization (hazard ratio [HR], 0.9 [95% confidence interval {CI}, 0.5-1.5]; P > .05) nor infection (HR, 1.2 [95% CI, 0.7-1.9]; P > .05) was associated with increased mortality risk. Infection caused by MRSA strains that were resistant to clindamycin and/or trimethoprim-sulfamethoxazole increased the mortality risk by 40% (HR, 1.4 [95% CI, 0.9-2.2]; P > .05), compared with the mortality risk of control subjects, but the increase was not statistically significant. MRSA infection independently increased length of stay by 40 days (95% CI, 34.2—45.6; P < .001) and was associated with an extra charge of $164,301 (95% CI, $158,712-$169,889; P < .001).Conclusions.MRSA colonization or infection in infants is associated with significant morbidity and financial burden but is not independently associated with increased mortality.

Candida species are the most common cause of fungal infections in hospitalized patients. Recent studies have reported a relative reduction in the rates of infection caused by Candida albicans and a shift toward non-albicans Candida spp. Data on the distribution and susceptibility of Candida spp. from children's hospitals are limited. Clinical isolates of Candida were collected from 4 US children's hospitals in 2003. Broth dilution MICs for amphotericin B, fluconazole, voriconazole, caspofungin, posaconazole, and ravuconazole were performed according to National Committee for Clinical Laboratory Standards-approved methodology. A total of 179 clinical isolates were identified and included. Of 179, 77 (43%) were C. albicans. Candida parapsilosis isolates were the second most frequently identified (57/175, 32%), followed by Candida glabrata, Candida tropicalis, and Candida lusitaniae (approximately 8% each). Caspofungin was the most active agent in vitro against all Candida spp. Fluconazole resistance was seen among C. glabrata, C. tropicalis, and Candida krusei isolates. Newer azoles had improved activity against fluconazole-resistant isolates of Candida. Among isolates of C. parapsilosis, nearly 20% were resistant to amphotericin B. The current study highlights the emergence of C. parapsilosis as a distinct pediatric pathogen with clinical and therapeutic implications. Furthermore, our current susceptibility data include newer antifungal agents that appear to be quite active in vitro and may provide new therapeutic options for the treatment of serious yeast infections in children.

A transformation affecting the workflow and information management in microbiology laboratories is the shift from diagnostic testing based on culture, antigen detection, antibody detection, and microscopy to a greater dependence upon molecular technologies. The responsibilities of the microbiology laboratory leadership team are becoming more informatics-centric as well. This chapter reviews the principles of laboratory informatics and the architecture of information system. A laboratory information system (LIS) consists of one or more servers that provide the array of services, and the information entered into, stored within, and reported from the LIS is directly or indirectly related to laboratory testing. Typically encountered interfaces between the LIS and other information systems include admission/discharge/transfer (ADT) interface and order-entry interface. Long-term storage and retrieval of laboratory data can be easily accommodated by a suitably configured LIS. The current emphasis by payors and healthcare accrediting agencies on utilization review of laboratory services and quality assurance analysis of laboratory testing requires that laboratory activity be evaluated on a regular basis. The chapter discusses the manner in which the LIS can serve to enhance the cost-effectiveness and accuracy of microbiology testing. The clinical laboratory, including the microbiology laboratory, is an ideal candidate for lean/Six Sigma reorganization. Leveraging the capabilities of the LIS to track bar-coded specimens, to connect with testing instruments to improve error-free data flow, and to display laboratory productivity snapshots on workstation dashboards are all important components of a program to pursue excellence in laboratory testing.

Traditionally, Streptococcus pneumoniae is identified in the laboratory by demonstrating susceptibility to optochin. Between 1992 and 1998, 4 pneumococcal isolates exhibiting optochin resistance were recovered from patients at Children's National Medical Center. Three of the 4 isolates consisted of mixed populations of optochin-resistant and -susceptible organisms. Both subpopulations had identical antibiograms, serotypes, and restriction fragment profiles. The other isolate was uniformly resistant to optochin. Resistant strains had MICs of optochin 4-30-fold higher than susceptible strains, belonged to different serotypes, and had dissimilar restriction fragment profiles, indicating clonal unrelatedness. Resistance arose from single point mutations in either the a-subunit (W206S) or the c-subunit (G20S, M23I, and A49T) of H(+)-ATPase. There is speculation of a possible association between exposure to antimalarial drugs and evolution of optochin resistance. alpha-Hemolytic streptococci resistant to optochin, particularly invasive isolates, should be tested for bile solubility or with an S. pneumoniae DNA probe before identification as viridans streptococci.

Nosocomial vancomycin-resistant Enterococcus (VRE) infections have been described in only small numbers of pediatric patients. In none of these studies were multivariate analyses performed to assess which factors were independent risk factors in these patients. In the present cohort study of patients admitted to our hematology/oncology unit, surveillance cultures revealed a colonization rate of 24% and all isolates were identified as Enterococcus faecium . Risk factors associated with colonization with VRE identified by multiple logistic regression analysis included young age and chemotherapy with antineoplastic agents, cefotaxime, vancomycin, and ceftazidime. A molecular epidemiological tool, pulsed-field gel electrophoresis, was used to determine the relatedness of the VRE isolates detected. DNA analysis by this method identified two major clusters of VRE isolates. Young children with gastrointestinal colonization with VRE, without evidence of clinical infection, can serve as a reservoir for the spread of VRE.

In the past week your team has been consulted to evaluate a 6-year-old boy with a febrile illness that progressed to altered mental status with seizures and a15-year old girl with recent behavioral changes, hallucinations and unusual facial movements. A resident on the general service that is managing both patients asks you if there is a standard diagnostic approach that can be taken with such patients that does not require ordering “too many tests.”

We assessed the antimicrobial susceptibilities of 59 penicillin-intermediate or penicillin-resistant pneumococci. All strains were susceptible to vancomycin and rifampicin. The frequency of strains with decreased susceptibility to cefotaxime, chloramphenicol, imipenem and meropenem was 15, 31, 47 and 49% respectively. The high percentage of penicillin-intermediate or penicillin-resistant Streptococcus pneumoniae with decreased susceptibility to third-generation cephalosporins, chloramphenicol and carbapenems limits the therapeutic options for the treatment of invasive pneumococcal infections and particularly of meningitis.

Please cite this paper as: Song et al. (2012) Comparison of pandemic and seasonal influenza A infections in pediatric patients: were they different?. Influenza and Other Respiratory Viruses 6(1), 25–27. This retrospective cohort study revealed that the presence of pandemic H1N1 influenza resulted in a 77.7% increase of patient visits in the emergency department for influenza like illnesses and a 67.2% increase of hospital days in our hospital by comparing to a regular influenza season (2008–2009 season). However, median length of hospital stay was no different in either period (pandemic: 3 days versus seasonal: 4 days, P = 0.06). Except for the patients hospitalized for pandemic H1N1 influenza (n = 111) were older (median age: 4.7 years versus 1.6 years, P = 0.04) and tended to have pre‐existing asthma (21.6% versus 9.0%, P = 0.07) than those hospitalized for seasonal influenza A infections (n = 44), this study found no significant difference between the two comparison groups with regards of other clinical and epidemiological features.

Human parechovirus-3 (HPeV-3) is an emerging pathogen that has been described as a cause of neonatal sepsis. Human parechoviruses are a family of viruses closely related to enteroviruses; however, enteroviral PCR will not detect HPeVs. We present clinical details of neonatal meningoencephalitis and hepatitis-coagulopathy syndrome caused by HPeV-3 infection.

Objective.To investigate the epidemiology of multidrug-resistant Enterobacteriaceae (MDRE) in hospitalized infants.Methods.From 2000 through 2005, active surveillance cultures for MDRE were performed for patients admitted to a 40-bed neonatal intensive care unit (NICU) that provides care for critically ill infants 6 months of age or younger. MDRE epidemiology and the genetic relatedness of MDRE strains determined by repetitive-sequence polymerase chain reaction were analyzed.Results.Active surveillance cultures revealed that 759 (23%) of 3,370 NICU infants (or approximately 1 in 5) developed MDRE colonization or infection and that 613 (72%) of the 853 isolates with epidemiologic data available were healthcare acquired. MDRE colonization occurred more frequently (in 653 infants [86%]) than did MDRE infection (in 106 [14%]). Of the 653 infants with MDRE colonization, 119 (18%) eventually became infected, with 29 (4%) acquiring sterile site infections. The most commonly isolated organisms were the Enterobacter species, accounting for 612 (71%) of the 862 isolates. Molecular epidemiologic analysis revealed that genetic-relatedness clustering (related clusters defined as having a genetic similarity coefficient greater than 95%) varied depending on microbial species. Clustering was detected for 36 (78%) of the 46 Enterobacter aerogenes isolates, 22 (45%) of the 49 Enterobacter cloacae isolates, and 13 (59%) of the 22 Klebsiella pneumoniae isolates.Conclusion.Hospitalized infants are at significant risk of acquiring MDRE, specifically Enterobacter species, at the study institution. Active surveillance cultures identified colonized patients who likely contributed to the institutional reservoir of MDRE. Molecular epidemiologic studies suggest that both patient-to-patient transmission and de novo acquisition of resistance play a role in the acquisition of these organisms, and that the clinical significance of such acquisition varies by species. The high percentage of E. aerogenes isolates that demonstrated genetic clustering suggests that monitoring the prevalence of this organism could serve as a useful measure of compliance with infection control procedures.

A total of 1092 clinical isolates of Haemophilus influenzae (306 type b; 786 non-type-b), from five medical centers were obtained during 1987 and 1988. Disk diffusion antimicrobial susceptibilities were obtained for all isolates, and broth microdilution susceptibilities were obtained for 502 isolates. Beta-lactamase was produced by 34.3% of type-b and 22.1% of non-type-b isolates, with some geographic variations. Using disk diffusion antimicrobial susceptibility testing, all isolates were susceptible to ampicillin-sulbactam, ceftriaxone, cefuroxime, and rifampin; two isolates were resistant to chloramphenicol. Whether tested using a fixed ratio of ampicillin to sulbactam of 2:1 or a fixed concentration of sulbactam, the ampicillin-sulbactam combination demonstrated good activity against clinical isolates of H. influenzae. Only 8 of the 1092 isolates did not produce beta-lactamase but demonstrated MICs of greater than or equal to 2 micrograms/ml for ampicillin.

Objective.To determine temporal trends in the incidence rate forClostridium difficile-associated disease (CDAD) in a pediatric patient population.Methods.We performed an observational, retrospective cohort study that included children who visited or were admitted to Children's National Medical Center during the period from July 2001 through June 2006. The CDAD incidence rates were determined and examined for changes over time using the Poisson regression method.Results.A total of 513 patients whose stool specimens tested positive forC. difficiletoxin were identified. Of these patients, 61% were children aged 2 years or older. The proportion of patients with CDAD in this age group has steadily increased from 46% in 2001 to 64% in 2006. Largely as a result of an increasing number of cases of community-associated CDAD, the incidence of CDAD increased significantly in the outpatient setting, particularly in the emergency department (1.18 cases per 1,000 visits in 2001 vs 2.47 cases per 1,000 visits in 2006;P= .02). The incidence among inpatients decreased during the study period (1.024 cases per 1,000 patient-days in 2001 vs 0.680 cases per 1,000 patient-days in 2006;P= .004). In the neonatal intensive care unit,C. difficile toxinwas detected in stool specimens collected from 22 patients aged from 15 days to 6 months.Conclusion.This study revealed a steady increase in the number of patients seen in the emergency department with community-acquired CDAD. Findings from this study suggest that the characteristics of CDAD in children—a population that has not been considered to be at high risk for this disease in the past—are changing. Further investigations are warranted to explore deviations from the established burdens of the disease and patient risk factors.

We report the descriptive and molecular epidemiology of vancomycin-resistant enterococci (VRE) infection and colonization and cocolonization with methicillin-resistant Staphylococcus aureus (MRSA) in children. Interunit and intraunit spread of VRE was detected, and 8 cases of VRE-MRSA cocolonization were identified. Seven of these cases were identified only via active surveillance, because clinical evidence of VRE colonization was absent.

Context.—Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine.Objective.—Children's Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs.Data Sources.—Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine.Conclusions.—Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training.

Repetitive sequence–based polymerase chain reaction fingerprinting was used to characterize 23 vancomycin-nonsusceptible enterococcal isolates from 2003 to 2004. Five genetically related clusters spanned geographically distinct referring centers. DNA fingerprinting showed infant-to-infant transmission from referring institutions. Thus, community healthcare facilities are a source of vancomycin-nonsusceptible enterococci and should be targeted for increased infection control efforts.

Background and Objective:Multidrug-resistant organisms (MDROs), such as vancomycin-resistant enterococci (VRE), cause serious infections, especially among high-risk patients in NICUs. When VRE was introduced and transmitted in our NICU despite recommended infection control practices, we instituted active surveillance cultures to determine their efficacy in detecting and controlling spread of VRE among high-risk infants.Methods:Active surveillance cultures, other infection control measures, and a mandatory in-service education module on preventing MDRO transmission were implemented. Cultures were performed on NICU admission and then weekly during their stay. Molecular DNA fingerprinting of VRE isolates facilitated targeting efforts to eliminate clonal spread of VRE. Repetitive sequence PCR (rep-PCR)-based DNA fingerprinting was used to compare isolates recovered from patients with VRE infection or colonization. Environmental VRE cultures were performed around VRE-colonized or -infected patients. DNA fingerprints were prepared from the products of rep-PCR amplification and analyzed using software to determine strain genetic relatedness.Results:Active surveillance cultures identified 65 patients with VRE colonization or infection among 1,820 admitted to the NICU. Rep-PCR performed on 60 VRE isolates identified 3 clusters. Cluster 1 included isolates from 21 patients and 4 isolates from the environment of the index patient. Clusters 2 and 3 included isolates from 23 and 3 patients, respectively. Similarity coefficients among the members of each cluster were 95% or greater.Conclusions:Control of transmission of multi-clonal VRE strains was achieved. Active surveillance cultures, together with implementation of other infection control measures, combined with rep-PCR DNA fingerprinting were instrumental in controlling VRE transmission in our NICU. (Infect Control Hosp Epidemiol 2005;26:646-649)

Publisher Summary The purpose of developing quality management guidelines for laboratories performing microbial forensic work is to promote the development of testing programs that are scientifically valid and rigorous, and to establish minimum operational criteria for application oriented laboratories. Criteria should be developed for the validation of microbial forensics methods that can be used for determining attribution during criminal investigations. Germane to this effort is the establishment of national guidelines for quality assurance and control that are relevant for microbial forensics laboratories. The activities carried out by microbial forensics and clinical laboratories overlap. The quality management guidelines under which clinical laboratories operate should have relevance for microbial forensics laboratories and serve as the basis for similar guidelines tailored to the needs of microbial forensics laboratories. Delivery of accurate, reproducible, and useful data should be the objective of every microbial forensics laboratory. The ability of a laboratory to achieve this objective is dependent upon many factors; such as, well-functioning quality management program. Quality means granting attention to each of the components of the quality management program.

Background. Several outbreaks of Pseudomonas aeruginosa infection associated with a specific model of fiberoptic bronchoscope have been reported. In a 3-week period in September 2000, we noticed an increased number of Trichosporon mucoides isolates recovered from bronchoalveolar lavage (BAL) specimens collected at our hospital. We investigated the circumstances surrounding these isolates. Methods. Outbreak investigation was conducted, and the medical records of the affected patients were reviewed retrospectively for evidence of positive cultures for T. mucoides from BAL specimens. Specimens collected during the investigation were inoculated onto fungal culture medium and yeasts were identified with API-20C (BioMerieux-Vitek). Results. During the 3-week period BAL specimens from six patients yielded growth of T. mucoides. These six high risk patients had emergency bronchoscopy performed as a workup for pneumonia and/or respiratory distress. A Model BF XP-40 bronchoscope (Olympus) had been used in all six patients. Cultures of the bronchoscope (external body and the lumen), bronchoscope disinfector, 2% glutaraldehyde disinfecting solution and water filters/supply were performed. Only fluid from the bronchoscope lumen yielded growth of T. mucoides. Air sample cultures of the bronchoscopy suites were negative. Medical records review disclosed that affected patients were not readmitted with infection with T. mucoides and had no adverse outcomes. The bronchoscope was removed from service and returned to the manufacturer. Conclusion. Routine surveillance and aggressive investigation identified persistent T. mucoides contamination of one bronchoscope. The bronchoscope manufacturer later recalled the BF XP-40 model for corrective revision.

To determine the risk factors associated with progression from colonization to infection with health care-associated antimicrobial-nonsusceptible Enterobacteriaceae (ANE) in critically ill neonates.During a 3-year period (1998 to 2000), surveillance rectal cultures were performed on neonates admitted to our Level III neonatal intensive care unit after a cluster of four cases of ANE infection were identified in 1998. ANE were defined as members of the Enterobacteriaceae family that exhibited nonsusceptibility to ceftazidime or laboratory evidence of extended spectrum beta-lactamase (ESBL) production.A total of 1,710 patients were admitted to the neonatal intensive care unit during the study period. Of the 1,710 patients 300 (18%) were excluded from the risk factor analysis. Of the 1,410 remaining neonates the incidence of health care-associated ANE colonization was 17% (240 of 1,410 patients), and 14% of the colonized patients (34 of 240 patients) developed ANE infections. Of the 206 ANE-colonized patients who did not develop disease, 60 (29%) harbored ESBL-producing isolates. Of the 34 ANE-infected patients, 14 (41%) yielded growth of ESBL-producing isolates. Multiple logistic regression analysis revealed that colonized neonates with very low birth weights (1,000 g) and those who had received prolonged exposures to antimicrobial agents were at increased risk of ANE infections.Colonization with ANE places hospitalized neonates at risk for development of systemic infections. Very low birth weight (1,000 g) and prolonged exposure to antimicrobial agents were the only two independent risk factors associated with ANE infection.