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This article provides a focused update to the clinical practice guideline on the treatment and management of patients with coronavirus disease 2019, developed by the Infectious Diseases Society of America. The guideline panel presents a recommendation on the use of the anti-severe acute respiratory syndrome coronavirus 2 neutralizing antibody pemivibart as pre-exposure prophylaxis. The recommendation is based on evidence derived from a systematic review and adheres to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Information on pemivibart is included in the U.S. Food and Drug Administration Emergency Use Authorization for this agent., Competing Interests: Possible conflicts of interest. Evaluation of relationships as potential conflicts of interest is determined by a review process. The assessment of disclosed relationships for possible COIs is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The following panelists have research-related advisor/consultant roles for indicated companies: R.B. for Shionogi, Merck, and Gilead Sciences; K.W.C. for Pardes Biosciences (concluded); E.D. for Gilead Sciences; D.V.G. for Gilead Sciences and Merck; A.K. for Shionogi; S.S. for Pfizer; P.T. for Merck and Shionogi. Importantly, these companies have developed COVID-19 treatment (but not prophylaxis) agents. No disclosures reported for all other authors including the chair and vice chair. Additional information. More detailed information on the analysis and development of recommendations is available in the Supplementary material., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Risk stratification is a cornerstone of the Pediatric Infectious Diseases Society COVID-19 treatment guidance. This systematic review and meta-analysis aimed to define the clinical characteristics and comorbidities associated with critical COVID-19 in children and adolescents., Methods: Two independent reviewers screened the literature (Medline and EMBASE) for studies published through August 31, 2023, that reported outcome data on patients aged ≤21 years with COVID-19. Critical disease was defined as an invasive mechanical ventilation requirement, intensive care unit admission, or death. Random-effects models were used to estimate pooled odds ratios (OR) with 95% confidence intervals (CI), and heterogeneity was explored through subgroup analyses., Results: Among 10,178 articles, 136 studies met the inclusion criteria for review. Data from 70 studies, which collectively examined 172,165 children and adolescents with COVID-19, were pooled for meta-analysis. In previously healthy children, the absolute risk of critical disease from COVID-19 was 4% (95% CI, 1%-10%). Compared with no comorbidities, the pooled OR for critical disease was 3.95 (95% CI, 2.78-5.63) for the presence of one comorbidity and 9.51 (95% CI, 5.62-16.06) for ≥2 comorbidities. Key risk factors included cardiovascular and neurological disorders, chronic pulmonary conditions (excluding asthma), diabetes, obesity, and immunocompromise, all with statistically significant ORs > 2.00., Conclusions: While the absolute risk for critical COVID-19 in children and adolescents without underlying health conditions is relatively low, the presence of one or more comorbidities was associated with markedly increased risk. These findings support the importance of risk stratification in tailoring pediatric COVID-19 management., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

There are many pharmacologic therapies that are being used or considered for treatment of coronavirus disease 2019 (COVID-19), with rapidly changing efficacy and safety evidence from trials. The objective was to develop evidence-based, rapid, living guidelines intended to support patients, clinicians, and other healthcare professionals in their decisions about treatment and management of patients with COVID-19. In March 2020, the Infectious Diseases Society of America (IDSA) formed a multidisciplinary guideline panel of infectious disease clinicians, pharmacists, and methodologists with varied areas of expertise to regularly review the evidence and make recommendations about the treatment and management of persons with COVID-19. The process used a living guideline approach and followed a rapid recommendation development checklist. The panel prioritized questions and outcomes. A systematic review of the peer-reviewed and grey literature was conducted at regular intervals. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of evidence and make recommendations. Based on the most recent search conducted on 31 May 2022, the IDSA guideline panel has made 32 recommendations for the treatment and management of the following groups/populations: pre- and postexposure prophylaxis, ambulatory with mild-to-moderate disease, and hospitalized with mild-to-moderate, severe but not critical, and critical disease. As these are living guidelines, the most recent recommendations can be found online at: https://idsociety.org/COVID19guidelines. At the inception of its work, the panel has expressed the overarching goal that patients be recruited into ongoing trials. Since then, many trials were conducted that provided much-needed evidence for COVID-19 therapies. There still remain many unanswered questions as the pandemic evolved, which we hope future trials can answer., Competing Interests: Potential conflicts of interest. The following list is a reflection of what has been reported to IDSA. To provide thorough transparency, IDSA requires full disclosure of all relationships, regardless of relevancy to the guideline topic. Evaluation of such relationships as potential conflicts of interest is determined by a review process which includes assessment by the Board of Directors liaison to the Standards and Practice Guidelines Committee and, if necessary, the Conflicts of Interest and Ethics Committee. The assessment of disclosed relationships for possible conflicts of interest is based on the relative weight of the financial relationship (ie, monetary amount) and the relevance of the relationship (ie, the degree to which an association might reasonably be interpreted by an independent observer as related to the topic or recommendation of consideration). The reader of these guidelines should be mindful of this when the list of disclosures is reviewed. L. B. receives research funding from the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID), Bill and Melinda Gates Foundation, Wellcome Trust, and Harvard Medical School; serves as chair of the Antimicrobial Drug Advisory Committee of the Food and Drug Administration; and is involved in HIV and COVID-19 vaccine clinical trials conducted in collaboration with the NIH, HIV Vaccine Trials Network, COVID Vaccine Prevention Network, International AIDS Vaccine Initiative, Crucell/Janssen Pharmaceuticals, Moderna, Military HIV Research Program, Bill and Melinda Gates Foundation, and the Ragon Institute. A. B. received an honorarium from the Institute for Clinical and Economic Review. V. C.-C. C. receives research funding from the Health and Medical Research Fund; serves on the Research Committee of the Society for Healthcare Epidemiology of America (SHEA); and serves on the international editorial boards for the Journal of Hospital Infection, Infection Prevention in Practice, and Antimicrobial Stewardship and Healthcare Epidemiology. K. M. E. serves as a scientific advisor for Merck, Bionet, IBM, Sanofi, X4 Pharmaceuticals, Inc, Seqirus, Inc, Moderna, Inc, GSK plc, Roche, and Pfizer; and receives research funding from the Centers for Disease Control and Prevention and the NIH. J. C. G. serves in an advisory role for Qpex, Shionogi, and Merck; receives research funding from Merck; previously served in an advisory role for Accelerate Diagnostics, Achaogen, Astellas Pharma, Melinta Therapeutics, Nabriva Therapeutics, Paratek Pharma, scPharmaceuticals, Spero Therapeutics, and Tetraphase Pharmaceuticals; and previously served on the speaker’s bureau for Astellas Pharma, Melinta Therapeutics, Merck, and Shionogi. R. T. G. serves as a panel member on the NIH COVID-19 Treatment Guidelines Panel; serves as the immediate Past Chair for the HIV Medicine Association; receives research funding from the NIH; and has served on the scientific advisory board for Gilead Sciences, Inc, and Merck. W. J. M. serves in an advisory role for Seqirus, Inc; receives research funding from Ansun Biopharma, Astellas Pharma, AstraZeneca, Eli Lilly and Company, Enanta Pharmaceuticals, Gilead Sciences, Janssen Pharmaceuticals, Karius, Melinta Therapeutics, Merck, Moderna, Nabriva Therapeutics, Paratek Pharma, Pfizer, Roche, and Tetraphase Pharmaceuticals; and has previously received research funding from Abbott Laboratories. M. H. M receives research funding from the Agency for Healthcare Research and Quality, the Endocrine Society, and the Society for Vascular Surgery; serves as a Board member for the Evidence Foundation; has received research funding from the American Society of Hematology and the World Health Organization (WHO); and has served as a guideline methodologist for the WHO. R. A. M. receives research funding from the NIH, the WHO, the American College of Rheumatology, the American Society of Hematology, and Bohringer Ingelheim; serves as Chair of the Midwest Comparative Effectiveness Public Advisory Council of the Institute for Clinical and Economic Review (ICER); serves on the Methods Committee for Kidney Disease Improving Global Outcomes Work Group; serves on the Clinical Guidelines Committee for the Canadian Society of Nephrology; and previously served on the Clinical Guidelines Committee for the American College of Physicians (ACP). M. M. N. co-chairs the Pediatric Infectious Diseases Society COVID-19 Therapies Task Force, will receive support to attend as a speaker the American Academy of Pediatrics National Conference & Exhibition in October 2022, and has received research funding from Gilead Sciences. J. C. O. serves as an advisor for Bates College; holds stocks in Doximity, Inc; receives research funding from the MITRE Corporation and Nference, Inc; and serves on committees for the Society for Critical Care Medicine, SHEA, and University Lake School. R. W. S. served in an advisory role for GSK plc and Gilead Sciences. S. Soham serves in advisory roles for Amplyx Pharmaceuticals, Inc, ReViral Ltd, Adamis Pharmaceuticals, and Immunome; holds stocks in Immunome; receives research funding from Ansun BioPharma, Zeteo Tech, Inc, F2G, Emergent Biosolutions, Shionogi, Shire (now Takeda), Cidara Therapeutics, US Department of Defense (Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense), Defense Health Agency, Bloomberg Philanthropies, the State of Maryland, NIH/NIAID, NIH National Center for Advancing Translational Sciences, Mental Wellness Foundation, Moriah Fund, Octopharma, HealthNetwork Foundation, Shear Family Foundation, Johns Hopkins University, and Mayo Clinic; serves as the Governor of the ACP; has received research funding from the University of Nebraska; and has served as an advisor for Janssen Pharmaceuticals, Acidophil, LLC, Adagio Therapeutics, Inc, Celltrion Healthcare, and Intermountain Health. A. H. S. receives research funding from the US Department of Veterans Affairs. S. Sultan serves on guideline panels for the American Gastroenterological Association (AGA) and receives research funding from the Department of Veterans Affairs Evidence Synthesis Program. Y. F.-Y. receives honoraria from the Evidence Foundation for evidence reviews and teaching, the AGA for evidence reviews, and ICER for committee meetings; serves as a Director for the Evidence Foundation and for the US GRADE Network; and served on an Independent Appraisal Committee for ICER. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Since November 2019, the SARS-CoV-2 pandemic has created challenges for preventing and managing COVID-19 in children and adolescents. Most research to develop new therapeutic interventions or to repurpose existing ones has been undertaken in adults, and although most cases of infection in pediatric populations are mild, there have been many cases of critical and fatal infection. Understanding the risk factors for severe illness and the evidence for safety, efficacy, and effectiveness of therapies for COVID-19 in children is necessary to optimize therapy., Methods: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacology, and pediatric intensive care medicine from 21 geographically diverse North American institutions was re-convened. Through a series of teleconferences and web-based surveys and a systematic review with meta-analysis of data for risk factors, a guidance statement comprising a series of recommendations for risk stratification, treatment, and prevention of COVID-19 was developed and refined based on expert consensus., Results: There are identifiable clinical characteristics that enable risk stratification for patients at risk for severe COVID-19. These risk factors can be used to guide the treatment of hospitalized and non-hospitalized children and adolescents with COVID-19 and to guide preventative therapy where options remain available., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Antimicrobial stewardship programs (ASPs) promote optimal antimicrobial use to prevent resistance, improve outcomes, and reduce costs. We explored how pediatric ASPs enact prospective audit and feedback (PAF) and preauthorization and characterized programs' perceptions of how these choices affected attainment of stewardship goals., Methods: We conducted focus groups with US pediatric ASP practitioners, organized by predominant strategy: PAF, preauthorization, or a hybrid. We asked open-ended questions about organization, staffing, and operation of these strategies, as well as rationales for and perceived advantages and disadvantages of these choices. We used applied thematic analysis to analyze transcripts, organizing coded text into themes and categories. We formulated a conceptual model for how the design and performance of PAF and preauthorization affect stewardship goals and stewards' work experiences., Results: Eighteen physicians and 14 pharmacists from 24 hospitals participated in five focus groups. Stewards described myriad advantages and limitations of PAF and preauthorization that support or detract from stewardship goals. For example, PAF uncovered institutional trends in antibiotic use and fostered relationship building but was time-consuming. Preauthorization efficiently reduced broad-spectrum antimicrobial use, yet offered limited educational opportunities. How these strategies facilitated or impeded appropriate antimicrobial use in turn affected stewards' professional satisfaction, creating a feedback loop that could reinforced positive or negative outcomes., Conclusions: ASPs reported differing emphasis on and implementation of PAF and preauthorization. Each strategy entailed contrasting benefits and trade-offs for steward satisfaction and perceived efficacy, suggesting that a hybrid approach could enable ASPs to maximize strengths of each to mitigate drawbacks of the other., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objective: This study aimed to develop and evaluate an algorithm to reduce the chart review burden of improvement efforts by automatically labeling antibiotic selection as either guideline-concordant or -discordant based on electronic health record data for patients with community-acquired pneumonia (CAP)., Methods: We developed a 3-part algorithm using structured and unstructured data to assess adherence to an institutional CAP clinical practice guideline. The algorithm was applied to retrospective data for patients seen with CAP from 2017 to 2019 at a tertiary children's hospital. Performance metrics included positive predictive value (precision), sensitivity (recall), and F1 score (harmonized mean), with macro-weighted averages. Two physician reviewers independently assigned "actual" labels based on manual chart review., Results: Of 1345 patients with CAP, 893 were included in the training cohort and 452 in the validation cohort. Overall, the model correctly labeled 435 of 452 (96%) patients. Of the 286 patients who met guideline inclusion criteria, 193 (68%) were labeled as having received guideline-concordant antibiotics, 48 (17%) were labeled as likely in a scenario in which deviation from the clinical practice guideline was appropriate, and 45 (16%) were given the final label of "possibly discordant, needs review." The sensitivity was 0.96, the positive predictive value was 0.97, and the F1 was 0.96., Conclusions: An automated algorithm that uses structured and unstructured electronic health record data can accurately assess the guideline concordance of antibiotic selection for CAP. This tool has the potential to improve the efficiency of improvement efforts by reducing the manual chart review needed for quality measurement., (Copyright © 2024 by the American Academy of Pediatrics.)

Objectives: We sought to create a digital application to support clinicians in empiric and pathogen-directed antibiotic ordering based on local susceptibility patterns and evidence-based treatment durations, thereby promoting antimicrobial stewardship., Methods: We formed a multidisciplinary team that met bimonthly from 2017 to 2018 to design and construct a web-based antimicrobial stewardship platform called Antibiogram + . We used an iterative and agile technical development process with frequent feedback from clinicians., Results: Antibiogram+ is an online tool, accessible via the electronic health record and hospital intranet, which offers institutional antibiotic susceptibilities for major pathogens, recommendations for empiric antibiotic selection and treatment durations for common pediatric conditions, antimicrobial dosing and monitoring guidance, and links to other internal clinical decision support resources. The tool was accessed 11,823 times with 492 average monthly views during the first 2 years after release. Compared with use of a preexisting print antibiogram and dosing card, pediatric residents more frequently reported "often" being sure of antibiotic dosing with Antibiogram+ (58 vs. 15%, p  < 0.01). Respondents also reported improved confidence in choice of antibiotic, but this finding did not reach statistical significance (55 vs. 35%, p  = 0.26)., Conclusion: We report the successful development of a digital antimicrobial stewardship platform with consistent rates of access during the first 2 years following release and improved provider comfort with antibiotic management., Competing Interests: None declared., (Thieme. All rights reserved.)

Penicillin allergy labels are common in hospitalized patients, and there is a frequent misconception that these patients cannot receive cephalosporins. Through retrospective review, we found that patients with reported penicillin allergies were significantly less likely to receive first-line therapy for acute hematogenous osteomyelitis., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Monoclonal antibodies for COVID-19 are authorized in high-risk patients aged ≥12 years, but evidence in pediatric patients is limited. In our cohort of 142 patients treated at seven pediatric hospitals between 12/1/20 and 7/31/21, 9% developed adverse events, 6% were admitted for COVID-19 within 30 days, and none received ventilatory support or died., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce., Methods: We evaluated children and adolescents aged <19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Based on qualifying microbiology results from the first 3 days of admission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes., Results: Of the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk [aRR], 1.34 [95% confidence interval {CI}, 1.01-1.79]), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 [95% CI, 1.05-1.90]), or those requiring invasive mechanical ventilation (aRR, 1.83 [95% CI, 1.36-2.47]) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 [95% CI, 1.15-4.62]) was associated with bacterial coinfection., Conclusions: Community-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely., Competing Interests: Potential conflicts of interest. K. L. M. reports receiving funds from ContraFect as site investigator of a drug study and as patent beneficiary of technology licensed to Affinivax, Inc, outside the submitted work. C. V. H. reports receiving funds from UpToDate, Dynamed.com, and bioMérieux, outside the submitted work. M. W. H. reports receiving licensing fees from Kiadis, consulting fees from AbbVie for service on a data and safety monitoring board, consulting fees from the American Board of Pediatrics for service on a subboard, fees from Sobi for participating in a drug study, and fees from Partner Therapeutics for participating in a drug study, outside the submitted work. E. R. L. reports receiving grants to the institution from the National Institute of Allergy and Infectious Diseases (NIAID; AI 144301-01) and the CDC (CDC 75D30120C07725-01). A. G. R. reports receiving grants from NIAID and funds from UpToDate for editorial work. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Clinical differences between critical illness from influenza infection vs coronavirus disease 2019 (COVID-19) have not been well characterized in pediatric patients., Methods: We compared demographics, clinical characteristics, and outcomes of US children (aged 8 months to 17 years) admitted to the intensive care or high-acuity unit with influenza or COVID-19. Using mixed-effects models, we assessed the odds of death or requiring life support for influenza vs COVID-19 after adjustment for age, sex, race and Hispanic origin, and underlying conditions including obesity., Results: Children with influenza (n = 179) were younger than those with COVID-19 (n = 381; median, 5.2 years vs 13.8 years), less likely to be non-Hispanic Black (14.5% vs 27.6%) or Hispanic (24.0% vs 36.2%), and less likely to have ≥1 underlying condition (66.4% vs 78.5%) or be obese (21.4% vs 42.2%), and a shorter hospital stay (median, 5 days vs 7 days). They were similarly likely to require invasive mechanical ventilation (both 30.2%), vasopressor support (19.6% and 19.9%), or extracorporeal membrane oxygenation (2.2% and 2.9%). Four children with influenza (2.2%) and 11 children with COVID-19 (2.9%) died. The odds of death or requiring life support in children with influenza vs COVID-19 were similar (adjusted odds ratio, 1.30; 95% confidence interval, .78-2.15; P = .32)., Conclusions: Despite differences in demographics and clinical characteristics of children with influenza or COVID-19, the frequency of life-threatening complications was similar. Our findings highlight the importance of implementing prevention measures to reduce transmission and disease severity of influenza and COVID-19., Competing Interests: Potential conflicts of interest. N. B. H. reports grants or contracts from Sanofi and Quidell outside of the submitted work and an educational grant for honorarium from Genentech. M. M. B. reports grants or contracts from the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke, Grifols Investigator Sponsored Research Grant, and NIH/ Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) outside of the submitted work and paid to institution. B. M. C. reports grants or contracts from the NIH, American Thoracic Society, and American Lung Association outside the submitted work and paid to institution and payment to author for expert testimony from Triplett Woolf Garretson, LLC. N. Z. C. reports grants or contracts from the NIH outside of the submitted work. H. R. F. reports grants or contracts from the NIH, National Heart, Lung, and Blood Institute (NHLBI), and NICHD outside of the submitted work; support for attending meetings and/or travel from the Society of Critical Care Medicine; participation on a data and safety monitoring board (DSMB) for a cardiothoracic surgery trial (single center) and a DSMB for an intrathecal chemotherapy trial; an unpaid position on the Michigan Thoracic Society Executive Committed and Pediatric Acute Lung Injury and Sepsis Investigators network Executive Committee; and the following other financial or nonfinancial interests: Lucira Health advisory committee and Aerogen Pharma advisory unfunded. M. W. H. reports grants or contracts from the NIH and royalties from Kiadis outside of the submitted work; participation on a DSMB or advisory board for AbbVie and La Jolla Pharmaceuticals (payment to author); and leadership or fiduciary role on the American Board of Pediatrics (payment to author). J. R. H. reports grants or contracts from the NIH–NICHD outside of the submitted work and participation on a DSMB for an institutional study at the University of Minnesota (no financial reimbursements). M. K. reports grants or contracts from the NIH outside of the submitted work to institution. E. R. L. reports grants or contracts from the NIH outside of the submitted work and paid to institution. M. M. Nakamura reports grants or contracts from Gilead for participation in their remdesivir trial. R. A. N. reports grants or contracts from the NIH outside of the submitted work. C. M. R. reports grants or contracts from the NIH outside of the submitted work and payment for honoraria to author for the Contemporary Critical Care Complications of SCT/Cellular Therapies Conference by MD Anderson. J. E. S. reports grants or contracts from Merck outside of the submitted work and paid to institution. M. S. Z. reports grants or contracts from the NIH outside of the submitted work and paid to institution. A. G. R. reports grants or contracts from the National Institute of Allergy and Infectious Diseases to institution outside of the submitted work; royalties or licenses from UpToDate as a Pediatric Critical Care Section Editor paid to author; and is an unpaid treasurer for International Sepsis Forum. M. L. C. reports grants or contracts to institution for projects unrelated to this work from the CDC. J.C.F. reports an NIH award unrelated to this study and paid to institution. C. V. H. reports payment or honoraria as a consultant for Biofire (bioMérieux). G. E. M. reports payment for expert testimony in a malpractice case involving influenza related death. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Vaccination coverage for infants with CHD is unknown, yet these patients are at high risk for morbidity and mortality associated with vaccine-preventable illnesses. We determined vaccination rates for this population and identified predictors of undervaccination. We prospectively enrolled infants with CHD born between 1 January, 2012 and 31 December, 2015, seen in a single-centre cardiology clinic between 15 February, 2016 and 28 February, 2017. We assessed vaccination during the first year of life. Subjects who by age 1 year received all routine immunisations recommended during the first 6 months of life were considered fully vaccinated. We also evaluated influenza vaccination during subjects' first eligible influenza season. We obtained immunisation histories from primary care providers and collected demographic and clinical data via a parent survey and chart review. We used multivariable logistic regression to identify predictors of undervaccination. Among 260 subjects, only 60% were fully vaccinated. Vaccination rates were lowest for influenza (64.6%), rotavirus (71.1%), and Haemophilus influenzae type b (79.3%). Cardiac surgery with cardiopulmonary bypass during the first year of life was associated with undervaccination (51.5% versus 76.4% fully vaccinated, adjusted odds ratio 2.1 [95% confidence interval 1.1-3.9]). Other predictors of undervaccination were out-of-state primary care (adjusted odds ratio 2.7 [1.5-4.9]), multiple comorbidities (≥2 versus 0-1, adjusted odds ratio 2.0 [1.1-3.6]), and hospitalisation for >25% of the first year of life (>25% versus ≤25%, adjusted odds ratio 2.1 [1.1-3.9]). Targeted quality improvement initiatives focused on improving vaccination coverage for these infants, especially surrounding cardiac surgery, are needed.

To our knowledge, late, late-onset group B streptococcal (GBS) meningitis in identical twins has yet to be reported. We describe a case of 14-week-old twins who developed fever hours apart and presented simultaneously to the emergency department 2 days later with seizures. Blood and cerebrospinal fluid (CSF) cultures from both infants were positive for GBS. Their clinical courses were highly similar, with magnetic resonance imaging (MRI) demonstrating ventriculitis and subdural empyema, complicated by clinical and subclinical seizures requiring quadruple antiepileptic treatment. The CSF was sterile for both on follow-up lumbar puncture 48 hours after the initial positive CSF culture. Both showed marked improvement on antimicrobial and antiepileptic therapy, with fever resolving after 5 days of therapy, control of seizures, and slowly improving MRI findings. Twin A received a 6-week course of penicillin, whereas twin B received 6 weeks plus an additional 10 days due to persistent left cochlear enhancement consistent with labyrinthitis. Evaluation for an underlying primary immunodeficiency was negative. Genomic analysis revealed that the patients' CSF GBS isolates were essentially identical and of capsular polysaccharide serotype Ia.

Objective: To identify subgroups likely to benefit from monoclonal antibody and antiviral therapy by evaluating the relationship between comorbidities and hospitalization among US adolescents with symptomatic coronavirus disease 2019 (COVID-19)., Study Design: We analyzed the relationship between presence of comorbidities and need for hospitalization within 28 days of COVID-19 diagnosis for adolescents aged 12-17 years listed in the Pediatric COVID-19 US registry, a multicenter retrospective cohort of US pediatric patients with COVID-19. Comorbidities assessed included obesity, chronic kidney disease (CKD), diabetes, immunosuppressive disease or treatment, sickle cell disease (SCD), heart disease, neurologic disease/neurodevelopmental disorders, and pulmonary disease (excluding patients with mild asthma). We used multivariable logistic regression to determine race/ethnicity-adjusted associations between comorbidities and hospitalization., Results: A total of 1877 patients met our inclusion criteria, of whom 284 (15%) were hospitalized within 28 days of their COVID-19 diagnosis. In a race/ethnicity-adjusted model, the following comorbidities were independently associated with increased odds of hospitalization: SCD (aOR, 6.9; 95% CI, 3.0-15.9), immunocompromising condition (aOR, 6.4; 95% CI, 3.8-10.8), obesity (aOR, 3.2; 95% CI, 2.1-4.9), diabetes (aOR, 3.0; 95% CI, 1.4-6.2), neurologic disease (aOR, 2.8; 95% CI, 1.8-4.3), and pulmonary disease (excluding mild asthma) (aOR, 1.9; 95% CI, 1.2-3.1). Heart disease and CKD were not independently associated with hospitalization., Conclusions: SCD, immunocompromising conditions, obesity, diabetes, neurologic disease, and pulmonary disease (excluding mild asthma) were associated with hospitalization for symptomatic COVID-19. Adolescents with acute COVID-19 and these comorbidities should be prioritized for consideration of therapy to avert hospitalization., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The epidemiology of orbital cellulitis likely has evolved due to the emergence of methicillin-resistant Staphylococcus aureus (MRSA) and the adoption of pneumococcal conjugate vaccination. In the absence of published guidelines, management is highly variable. We characterized epidemiology and management over an 11-year period., Methods: A retrospective cohort study of children 0 to 21 years of age with orbital cellulitis +/- subperiosteal orbital abscess hospitalized at a large quaternary children's hospital from January 2008 to June 2018. We reviewed charts for demographic characteristics, clinical features, management, and outcomes. Using multivariable logistic regression, we evaluated predictors of surgical intervention and assessed whether corticosteroid use or antibiotic duration was related to clinical outcomes., Results: Among 220 patients, methicillin-susceptible S. aureus was the most common organism (26.3%), with MRSA found in only 5.0%. Rates of vancomycin use fluctuated annually from 40.9% to 84.6%. Surgery was performed in 39.5% of the patients. Corticosteroids, used in 70 patients (32.1%), were unrelated to treatment failure (n = 9), defined as persistent signs and symptoms or initial clinical improvement followed by worsening (P = .137). The median antibiotic duration was 17 days (interquartile range 14-26). After controlling for age, gender, proptosis, eye pain with movement, eyelid swelling, neutrophil count, and corticosteroid use, treatment failure was not significantly associated with receipt of ≥ 3 weeks of antibiotic therapy (8/84, 9.5%) compared with > 2 but < 3 weeks (0/51, 0.0%) or ≤ 2 weeks (1/85, 1.2%) (adjusted odds ratio = 5.83 for ≥ 3 vs ≤2 weeks; 95% confidence interval: 0.58, 59.0)., Conclusions: Although MRSA was rare, empiric vancomycin use was high. Treatment failure was uncommon in patients who received ≤ 2 weeks of therapy, suggesting that shorter durations are adequate in some patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Starting in November 2020, the US Food and Drug Administration (FDA) has issued Emergency Use Authorizations (EUAs) for multiple novel virus-neutralizing monoclonal antibody therapies, including bamlanivimab monotherapy (now revoked), bamlanivimab and etesivimab, casirivimab and imdevimab (REGEN-COV), and sotrovimab, for treatment or postexposure prophylaxis of Coronavirus disease 2019 (COVID-19) in adolescents (≥12 years of age) and adults with certain high-risk conditions. Previous guidance is now updated based on new evidence and clinical experience., Methods: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacotherapy, and pediatric critical care medicine from 18 geographically diverse US institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on a review of the best available evidence and expert opinion., Results: The course of COVID-19 in children and adolescents is typically mild, though more severe disease is occasionally observed. Evidence supporting risk stratification is incomplete. Randomized controlled trials have demonstrated the benefit of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific monoclonal antibody therapies in adults, but data on safety and efficacy in children or adolescents are limited. Potential harms associated with infusion reactions or anaphylaxis are reportedly low in adults., Conclusions: Based on evidence available as of August 31, 2021, the panel suggests a risk-based approach to administration of SARS-CoV-2 monoclonal antibody therapy. Therapy is suggested for the treatment of mild to moderate COVID-19 in adolescents (≥12 years of age) at the highest risk of progression to hospitalization or severe disease. Therapeutic decision-making about those at moderate risk of severe disease should be individualized. Use as postexposure prophylaxis could be considered for those at the highest risk who have a high-risk exposure but are not yet diagnosed with COVID-19. Clinicians and health systems should ensure safe and timely implementation of these therapeutics that does not exacerbate existing healthcare disparities., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Broad-range PCR (BRPCR) sequencing is a promising tool for diagnosis of infectious conditions when traditional microbiologic strategies fail to identify a pathogen. Data on the optimal clinical scenarios in which to use this tool are limited. We assessed, via retrospective chart review, the rate of organism identification and impact on clinical management from BRPCR testing sent from our quaternary care children's hospital between February 2010 and June 2020. A total of 382 samples were sent from 269 individual patients. A total of 200 (74.3%) patients were immunocompromised. Median age at time of sample collection was 10.0 years (interquartile range, 4.2 to 15.8). A total of 254/377 (64.7%) samples were from patients known to be on ≥1 antimicrobial in the 24 h prior to sample collection. A total of 112/382 (29.3%) samples were from patients ultimately diagnosed with a bacterial or fungal infection by another testing modality. The most common sample types were bronchoalveolar lavage (BAL) fluid (45), lung tissue (41), and bone (39). An organism was identified from 83 (21.7%) samples, but results from only 19 (5.0%) samples led to a change in management. Organisms were identified from 18 (40%) BAL samples; only 2 (4.4%) were judged to be clinically significant. A total of 4/12 (33.3%) samples from cardiac hardware changed clinical management. We found that only 5% of BRPCR results influenced antimicrobial management in a diverse pediatric cohort. Our findings suggest that the impact on clinical management varied widely by sample type. Additional work is necessary to characterize the ideal clinical scenarios in which BRPCR should be used.

Invasive aspergillosis (IA) remains a common cause of mortality in pediatric immunocompromised populations. Much of our knowledge of IA stems from adult literature. We conducted a retrospective evaluation of cases of proven or probable IA, defined according to the 2019 EORTC/MSG criteria, in patients with underlying immunocompromising conditions at Boston Children's Hospital from January 1, 2007 to January 1, 2019. We estimated survival curves over 12 weeks using the Kaplan-Meier method for all-cause mortality, and we used univariate Cox proportional hazards modeling to evaluate for mortality risk factors. We identified 59 cases, 29% with proven and 71% with probable IA. Pulmonary IA was the most common presentation (78%). The median age at diagnosis was 11 years (range, 0.5-28). Hematopoietic cell transplantation (HCT) was the most frequent predisposing underlying condition (41%). Among affected patients, 44.8% were neutropenic and 59.3% were lymphopenic at diagnosis. The 12-week all-cause mortality rate was 25.4%; HCT recipients comprised the majority of deaths (9/15) with a hazard ratio of 2.47 [95% CI, 0.87-6.95]. No patients with congenital immunodeficiencies (n = 8) died within 12 weeks of IA diagnosis. Other risk factors that were significantly associated with mortality included mechanical ventilation at diagnosis, intensive care unit stay, and lymphopenia; treatment with an Aspergillus-active azole was associated with decreased mortality.In conclusion, our study found that in pediatric immunocompromised hosts, IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the HCT population., Lay Abstract: This study explores the epidemiology, outcomes and predictors of mortality of invasive aspergillosis (IA) at a high-volume pediatric center for immunocompromised hosts. Much of our understanding of pediatric IA is extrapolated from the adult literature. Our study found that IA is associated with a high 12-week all-cause mortality rate, with a particular impact on the hematopoietic cell transplantation study cohort., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Ceftriaxone is one of the most common antibiotics prescribed for hospitalized children in the United States. However, ceftriaxone is not dosed consistently. Sepsis/serious bacterial infection had high dosing variability. Dosing for central nervous system infection was frequently suboptimal. Future efforts should focus on optimizing and standardizing ceftriaxone dosing., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for 2 novel virus-neutralizing monoclonal antibody therapies, bamlanivimab and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adolescents and adults in specified high-risk groups. This has challenged clinicians to determine the best approach to use of these products., Methods: A panel of experts in pediatric infectious diseases, pediatric infectious diseases pharmacy, pediatric intensive care medicine, and pediatric hematology from 29 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a guidance statement was developed and refined based on review of the best available evidence and expert opinion., Results: The course of COVID-19 in children and adolescents is typically mild and there is no high-quality evidence supporting any high-risk groups. There is no evidence for safety and efficacy of monoclonal antibody therapy for treatment of COVID-19 in children or adolescents, limited evidence of modest benefit in adults, and evidence for potential harm associated with infusion reactions or anaphylaxis., Conclusions: Based on evidence available as of December 20, 2020, the panel suggests against routine administration of monoclonal antibody therapy (bamlanivimab, or casirivimab and imdevimab), for treatment of COVID-19 in children or adolescents, including those designated by the FDA as at high risk of progression to hospitalization or severe disease. Clinicians and health systems choosing to use these agents on an individualized basis should consider risk factors supported by pediatric-specific evidence and ensure the implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although coronavirus disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data describing agents with potential antiviral activity continue to expand such that updated guidance is needed regarding use of these agents in children., Methods: A panel of pediatric infectious diseases physicians and pharmacists from 20 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of the best available evidence and expert opinion., Results: Given the typically mild course of COVID-19 in children, supportive care alone is suggested for most cases. For children with severe illness, defined as a supplemental oxygen requirement without need for noninvasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO), remdesivir is suggested, preferably as part of a clinical trial if available. Remdesivir should also be considered for critically ill children requiring invasive or noninvasive mechanical ventilation or ECMO. A duration of 5 days is appropriate for most patients. The panel recommends against the use of hydroxychloroquine or lopinavir-ritonavir (or other protease inhibitors) for COVID-19 in children., Conclusions: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For children with severe or critical disease, this guidance offers an approach for decision-making regarding use of remdesivir., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Although coronavirus disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develop severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics., Methods: A panel of pediatric infectious diseases physicians and pharmacists from 18 geographically diverse North American institutions was convened. Through a series of teleconferences and web-based surveys, a set of guidance statements was developed and refined based on review of best available evidence and expert opinion., Results: Given the typically mild course of pediatric COVID-19, supportive care alone is suggested for the overwhelming majority of cases. The panel suggests a decision-making framework for antiviral therapy that weighs risks and benefits based on disease severity as indicated by respiratory support needs, with consideration on a case-by-case basis of potential pediatric risk factors for disease progression. If an antiviral is used, the panel suggests remdesivir as the preferred agent. Hydroxychloroquine could be considered for patients who are not candidates for remdesivir or when remdesivir is not available. Antivirals should preferably be used as part of a clinical trial if available., Conclusions: Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare cases of severe or critical disease, this guidance offers an approach for decision-making regarding antivirals, informed by available data. As evidence continues to evolve rapidly, the need for updates to the guidance is anticipated., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To explore resident and attending physician perceptions of resident behaviors and skills that demonstrate trustworthiness and promote entrustment by supervisors., Method: Using grounded theory methodology, the authors conducted 3 focus groups with pediatric residents from the Boston Combined Residency Program and 3 focus groups with attending physicians who were either general pediatric hospitalists or other pediatric subspecialists at Boston Children's Hospital and Boston Medical Center in Boston, Massachusetts, from May to December 2018. Data were collected and analyzed iteratively until theoretical saturation was achieved. Three independent reviewers coded each transcript. Codes were grouped into dominant themes to develop a conceptual model., Results: Twelve residents and 18 attending physicians participated in the focus groups. Participants described actions that they felt actively demonstrated residents' trustworthiness within previously described domains of trustworthiness. Four modifiers emerged that affect a resident's progression from trustworthiness to entrustment: (1) self-management, (2) relationships, (3) self-advocacy, and (4) patient-centeredness. Findings were synthesized into a conceptual model depicting how trainees can promote their own entrustment by supervisors., Conclusions: Trainees must actively demonstrate their trustworthiness to be entrusted. This study proposes that trainees can further gain entrustment through self-management, relationships, self-advocacy, and patient-centeredness. When they understand the actions and behaviors that promote entrustment, trainees may be better able to foster autonomy and progress toward more independent clinical practice. These findings add to existing evidence regarding entrustment and provide a novel, actionable framework for trainees to increase their own entrustment.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Objective: Comparison of readmission rates requires adjustment for case-mix (ie, differences in patient populations), but previously only claims data were available for this purpose. We examined whether incorporation of relatively readily available clinical data improves prediction of pediatric readmissions and thus might enhance case-mix adjustment., Methods: We examined 30-day readmissions using claims and electronic health record data for patients ≤18 years and 29 days of age who were admitted to 3 children's hospitals from February 2011 to February 2014. Using the Pediatric All-Condition Readmission Measure and starting with a model including age, gender, chronic conditions, and primary diagnosis, we examined whether the addition of initial vital sign and laboratory data improved model performance. We employed machine learning to evaluate the same variables, using the L2-regularized logistic regression with cost-sensitive learning and convolutional neural network., Results: Controlling for the core model variables, low red blood cell count and mean corpuscular hemoglobin concentration and high red cell distribution width were associated with greater readmission risk, as were certain interactions between laboratory and chronic condition variables. However, the C-statistic (0.722 vs 0.713) and McFadden's pseudo R 2 (0.085 vs 0.076) for this and the core model were similar, suggesting minimal improvement in performance. In machine learning analyses, the F-measure (harmonic mean of sensitivity and positive predictive value) was similar for the best-performing model (containing all variables) and core model (0.250 vs 0.243)., Conclusions: Readily available clinical variables do not meaningfully improve the prediction of pediatric readmissions and would be unlikely to enhance case-mix adjustment unless their distributions varied widely across hospitals., (Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objectives: Moxifloxacin is not approved by the US Food and Drug Administration for pediatric use. Although its use might be indicated under certain conditions, data regarding its safety and tolerability in pediatric patients are limited. The primary objective of this study was to evaluate the safety of systemic moxifloxacin therapy in children., Methods: We conducted a retrospective observational study of patients aged <18 years who received oral or intravenous moxifloxacin at our institution between January 2011 and July 2016. Patient demographics, clinical characteristics, indication for moxifloxacin use, and adverse events (AEs) were extracted via chart review. The attribution of AEs to moxifloxacin use was adjudicated in consultation with a pediatric infectious disease (ID) pharmacist., Results: We identified 221 patients who received 300 courses of moxifloxacin. The average age at moxifloxacin initiation was 10.4 years. One or more AEs occurred during 195 (65%) of the courses. Of the 463 distinct AEs, 46 (9.9%) were attributed to moxifloxacin. AEs attributed to moxifloxacin included corrected QT interval (QTc) prolongation (18 [6%] courses), transaminase level elevation (7 [2.3%] courses), and increased bilirubin level (3 [1%] courses). AEs led to moxifloxacin discontinuation in 18 (6%) courses. ID consultation was associated with QTc (P < .001) and transaminase (P = .002) monitoring., Conclusions: AEs that occur during pediatric moxifloxacin therapy are relatively common but rarely serious enough to require premature discontinuation. The drug might be used safely in most children with monitoring, including evaluation for QTc prolongation, and guidance from ID specialists.

Background and Objective: Outpatient parenteral antimicrobial therapy (OPAT) provides numerous benefits but may pose unique risks in children. We aimed to determine rates of OPAT antimicrobial- and intravenous access-related complications and their associations with specific antimicrobials and type of intravenous access in pediatric patients., Methods: Observational cohort study of patients receiving OPAT from August 2008 to May 2015 cared for by the Infectious Diseases service at a tertiary children's hospital. Primary outcome was antimicrobial discontinuation (AD) because of OPAT-associated complications. Secondary outcomes were unplanned outpatient healthcare visits and readmissions from OPAT-associated complications., Results: Seven hundred and seven intravenous antimicrobials were prescribed in 540 cases. Nondevice-associated musculoskeletal infection was the most common diagnosis (39%). Ceftriaxone (30%), cefazolin (27%) and vancomycin (22%) were the most commonly used antimicrobials. Complications led to AD, ≥1 unplanned outpatient healthcare visit and ≥1 readmission in 23%, 30% and 17% of cases, respectively. Compared with use of ceftriaxone, use of oxacillin was associated with a significantly higher risk of AD because of any antimicrobial-related complication [hazard ratio (HR), 3.3; 95% confidence interval (CI): 1.2-9.7) and because of hepatic transaminitis (HR, 32.8; 95% CI: 4.02-268.2). Subjects treated with intravenous clindamycin (HR, 2.6; 95% CI: 1.1-5.8) and with a peripherally inserted central catheter (HR, 2.6; 95% CI: 1.04-6.3) were more likely to have unplanned outpatient visits., Conclusions: Use of oxacillin during OPAT was associated with higher rate of AD. Patients treated with clindamycin and those with a peripherally inserted central catheter had higher rates of unplanned outpatient visits. Providers should strongly consider alternative treatment options when possible.

Background and Objectives: Reducing readmissions is a major health care system goal. There is a gap in our understanding of pediatric readmission patterns after mental health (MH) admissions. With this study, we aimed to characterize the prevalence of readmissions after MH admissions, to identify patient-level factors and costs associated with readmissions, and to assess variation in readmission rates across hospitals., Methods: Using the 2014 Healthcare Cost and Utilization Project all-payer Nationwide Readmissions Database, we conducted a retrospective cohort analysis of 253 309 admissions for 5- to 17-year-olds at acute-care hospitals in 22 states. We calculated 30-day unplanned readmission rates, lengths of stay, and costs by primary admission diagnosis. We used hierarchical regression models to assess differences in readmission rates by patient characteristics, primary diagnoses, and comorbid chronic conditions, and to estimate the variation in case mix-adjusted rates across hospitals., Results: MH stays accounted for 18.7% ( n = 47 397) of index admissions. The 30-day readmission rate for MH admissions was higher than for non-MH admissions (8.0% vs 6.2%; P < .001). Children who were ≤14 years old, had non-MH chronic conditions, and/or had public insurance were more likely to be readmitted than their peers ( P < .001 for each). Adjusted rates varied across hospitals ( P < .001) and were 97.9% greater for hospitals 1 SD above versus below (11.2% vs 5.6%) the mean. Adjusted readmission rates, lengths of stay, and costs differed by diagnosis ( P < .001)., Conclusions: The 30-day readmission rate was significantly higher after MH than non-MH admissions. Adjusted MH readmission rates varied substantially among hospitals, suggesting potential room for improvement., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Background and Objective: Lower respiratory infections (LRIs) are among the most common reasons for pediatric hospitalization and among the diagnoses with the highest number of readmissions. Characterizing LRI readmissions would help guide efforts to prevent them. We assessed variation in pediatric LRI readmission rates, risk factors for readmission, and readmission diagnoses., Methods: We analyzed 2008-2009 Medicaid Analytic eXtract data for patients <18 years of age in 26 states. We identified LRI hospitalizations based on a primary diagnosis of bronchiolitis, influenza, or community-acquired pneumonia or a secondary diagnosis of one of these LRIs plus a primary diagnosis of asthma, respiratory failure, or sepsis/bacteremia. Readmission rates were calculated as the proportion of hospitalizations followed by ≥1 unplanned readmission within 30 days. We used logistic regression with fixed effects for patient characteristics and a hospital random intercept to case-mix adjust rates and assess risk factors., Results: Of 150 590 LRI hospitalizations, 8233 (5.5%) were followed by ≥1 readmission. The median adjusted hospital readmission rate was 5.2% (interquartile range: 5.1%-5.4%), and rates varied across hospitals ( P < .0001). Infants (patients <1 year of age), boys, and children with chronic conditions were more likely to be readmitted. The most common primary diagnoses on readmission were LRIs (48.2%), asthma (10.0%), fluid/electrolyte disorders (3.4%), respiratory failure (3.3%), and upper respiratory infections (2.7%)., Conclusions: LRI readmissions are common and vary across hospitals. Multiple risk factors are associated with readmission, indicating potential targets for strategies to reduce readmissions. Readmission diagnoses sometimes seem related to the original LRI., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Importance: Health care systems, payers, and hospitals use hospital readmission rates as a measure of quality. Although hospitals can track readmissions back to themselves (hospital A to hospital A), they lack information when their patients are readmitted to different hospitals (hospital A to hospital B). Because hospitals lack different-hospital readmission (DHR) data, they may underestimate all-hospital readmission (AHR) rates (hospital A to hospital A or B)., Objectives: To determine the prevalence of 30-day pediatric DHRs; to assess the effect of DHR on readmission performance; and to identify patient and hospital characteristics associated with DHR., Design, Setting, and Participants: We analyzed all-payer inpatient claims for 701,263 pediatric discharges (patients aged 0-17 years) from 177 acute care hospitals in New York State from January 1, 2005, through November 30, 2009, to identify 30-day same-hospital readmissions (SHRs), DHRs, and AHRs. Data analysis was performed from March 12, 2013, through April 6, 2015. We compared excess readmission ratios (calculated per the Medicare formula) using SHRs and AHRs to determine what might happen if the federal formula were applied to a specific state and to evaluate how often hospitals might accurately anticipate-using data available to them--whether they would incur penalties (excess readmission ratio >1) for readmissions. Using multivariate logistic regression, we identified patient- and hospital-level predictors of DHR vs SHR., Main Outcomes and Measures: The proportion of DHRs vs SHRs, AHR and SHR rates, and excess readmissions., Results: Different-hospital readmissions constituted 13.9% of 31,325 AHRs. At the individual hospital level, the median (interquartile range) percentage of DHRs was 21.6% (12.8%-39.1%). The median (interquartile range) adjusted AHR rate was 3.4% (3.0%-4.1%), 38.9% higher than the median adjusted SHR rate of 2.5% (2.0%-3.4%) (P < .001). Excess readmission ratios using SHRs inaccurately anticipated penalties (changed from >1 to ≤ 1 or vice versa) for 20 of the 177 hospitals (11.3%); all were nonchildren's hospitals and 18 of 20 (90.0%) were nonteaching hospitals. Characteristics associated with higher odds ratios (ORs) (reported with 95% CIs) of DHR in multivariate analyses included being younger (compared with age <1 year, ORs [95% CIs] for the other age categories ranged from 0.76 [0.66-0.88] to 0.85 [0.73-0.99]); being white (ORs [95% CIs] for nonwhite race/ethnicity ranged from 0.74 [0.65-0.84] to 0.88 [0.79-0.99]); having private insurance (1.14 [1.04-1.24]); having a chronic condition indicator for a mental disorder (1.33 [1.13-1.56]) or a disease of the nervous system (1.37 [1.20-1.57]) or circulatory system (1.20 [1.00-1.43]); and admission to a nonchildren's (1.62 [1.01-2.60]), urban (ORs for nonurban hospitals ranged from 0.35 [0.24-0.52] to 0.36 [0.21-0.64]), or lower-volume (0.73 [0.64-0.84]) hospital (P < .05 for each)., Conclusions and Relevance: Different-hospital readmissions differentially affect hospitals' pediatric readmission rates and anticipated performance, making SHRs an incomplete surrogate for AHRs-particularly for certain hospital types. Failing to incorporate DHRs into readmission measurement may impede quality assessment, anticipation of penalties, and quality improvement.

Background and Objective: Among children's hospitals, little is known about how barriers to electronic health record (EHR) adoption are related to meaningful use (MU) incentives. We investigated hospital success with MU incentive payments and determined associations with hospital-reported challenges and characteristics., Methods: A survey administered to 224 Children's Hospital Association hospitals assessed a variety of potential challenges to achieving meaningful EHR use (eg, lack of access to capital) and specific MU criteria that would be challenging to fulfill (eg, implement clinical decision support rules). These results were combined with data on hospitals that received MU payments up to March 2014 and information on hospital characteristics. Associations between anticipated challenges, children's hospital type, and receipt of MU incentives were evaluated in bivariate and multivariate analyses., Results: One hundred thirty-three children hospitals completed the survey (response rate 59.4%). Thirty-five percent of responding children's hospitals received MU incentive payments. The most frequently anticipated hospital challenges included the following: exchange clinical information with other providers outside your hospital system (49%), and generate numerator and denominator data for quality reporting directly from EHR (41%). Freestanding children's hospitals were more likely to indicate lack of relevance of MU criteria to pediatric care (odds ratio: 37.6 [95% confidence interval: 4.6-309.3]) and more likely to receive MU incentive payments (odds ratio: 26 [95% confidence interval: 5.2-130.6])., Conclusions: As of 2014, a minority of children's hospitals have successfully received MU incentive payments. Freestanding children's hospitals are more likely to report MU is not relevant to pediatric care and to succeed with MU incentive payments., (Copyright © 2015 by the American Academy of Pediatrics.)

Objective: We determined adoption rates of pediatric-oriented electronic health record (EHR) features by US children's hospitals and assessed perceptions regarding the suitability of commercial EHRs for pediatric care and the influence of the meaningful use incentive program on implementation of pediatric-oriented features., Materials and Methods: We surveyed members of the Children's Hospital Association. We measured adoption of 19 pediatric-oriented features and asked whether commercial EHRs include key pediatric-focused capabilities. We inquired about the meaningful use program's relevance to pediatrics and its influence on EHR implementation priorities., Results: Of 164 general acute care children's hospitals, 100 (61%) responded to the survey. Rates of comprehensive (across all pediatric units) adoption ranged from 37% (age-, gender-, and weight-adjusted blood pressure percentiles and immunization contraindication warnings) to 87% (age in appropriate units). Implementation rates for several features varied significantly by children's hospital type. Nearly 60% of hospitals reported having EHRs that do not contain all features essential for high-quality care. A majority of hospitals indicated that the meaningful use program has had no effect on their adoption of pediatric features, while 26% said they have delayed or forgone incorporation of such features because of the program., Conclusions: Children's hospitals are implementing pediatric-focused features, but a sizable proportion still finds their systems suboptimal for pediatric care. The meaningful use incentive program is failing to promote and in some cases delaying uptake of pediatric-oriented features., (© The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To assess the current state of quality improvement and patient safety (QIPS) education at a large teaching hospital., Methods: We surveyed 429 trainees (138 residents, 291 clinical fellows) and 38 program directors (PDs; 2 were PDs of >1 program) from 39 Accreditation Council for Graduate Medical Education-accredited training programs., Results: Twenty-nine PDs (76.3%) and 259 trainees (60.3%) responded. Most trainees (68.8%) reported participation in projects culminating in scholarly products (39.9%) or clinical innovations (44%). Most PDs reported that teaching (88.9%) and project supervision (83.3%) are performed by expert faculty. Nearly half of the PDs (45.8%) and trainees (49.6%) perceived project-based learning to be of equal value to formal curricula. Compared with trainees, a greater proportion of PDs reported needs for funding for projects, teaching faculty to provide mentorship, and faculty development (P < .05)., Conclusions: Providing additional financial, administrative, and operational support could enhance the value of curricula and projects. Developing expert teaching faculty is paramount., (© The Author(s) 2014.)

The Pediatric Quality Measures Program is developing readmission measures for pediatric use. We sought to describe the importance of readmissions in children and the challenges of developing readmission quality measures. We consider findings and perspectives from research studies and commentaries in the pediatric and adult literature, characterizing arguments for and against using readmission rates as measures of pediatric quality and discussing available evidence and current knowledge gaps. The major topic of debate regarding readmission rates as pediatric quality measures is the relative influence of hospital quality versus other factors within and outside of health systems on readmission risk. The complex causation of readmissions leads to disagreement, particularly when rates are publicly reported or tied to payment, about whether readmissions can be prevented and how to achieve fair comparisons of readmission performance. Despite these controversies, the policy focus on readmissions has motivated widespread efforts by hospitals and outpatient providers to evaluate and reengineer care processes. Many adult studies demonstrate a link between successful initiatives to improve quality and reductions in readmissions. More research is needed on methods to enhance adjustment of readmission rates and on how to prevent pediatric readmissions., (Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objective: We sought to explore the claims data-related issues relevant to quality measure development for Medicaid and the Children's Health Insurance Program (CHIP), illustrating the challenges encountered and solutions developed around 3 distinct performance measure topics: care coordination for children with complex needs, quality of care for high-prevalence conditions, and hospital readmissions., Methods: Each of 3 centers of excellence presents an example that illustrates the challenges of using claims data for quality measurement., Results: Our Centers of Excellence in pediatric quality measurement used innovative methods to develop algorithms that use Medicaid claims data to identify children with complex needs; overcome some shortcomings of existing data for measuring quality of care for common conditions such as otitis media; and identify readmissions after hospitalizations for lower respiratory infections., Conclusions: Our experience constructing quality measure specifications using claims data suggests that it will be challenging to measure key quality of care constructs for Medicaid-insured children at a national level in a timely and consistent way. Without better data to underpin pediatric quality measurement, Medicaid and CHIP will have difficulty using some existing measures for accountability, value-based purchasing, and quality improvement both across states and within states., (Copyright © 2014 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Unlabelled: OBJECTIVES To assess electronic health record (EHR) adoption and meaningful use among US children's hospitals through 2011 and compare these outcomes with adult hospitals and among subgroups of children's hospitals. We hypothesized that children's hospitals would show progress since our initial evaluation of health information technology (HIT) implementation in 2008., Methods: We identified children's hospitals using the membership directory of the Children's Hospital Association and analyzed their responses from 2008 to 2011 to the American Hospital Association's annual HIT survey. EHR adoption rates were determined by using previously specified definitions of the essential functionalities comprising an EHR. Achievement of meaningful use was evaluated based on hospitals' ability to fulfill 12 core meaningful use criteria. We compared these outcomes in 2011 between children's and adult hospitals and among subgroups of children's hospitals., Results: Of 162 children's hospitals, 126 (78%) responded to the survey in 2011. The proportion of children's hospitals with an EHR increased from 21% (in 2008) to 59% (in 2011). In 2011, 29% of children's hospitals met the 12 core criteria in our meaningful use proxy measure. EHR adoption rates and meaningful use were significantly higher for children's hospitals than for adult hospitals as a whole but similar for children's and adult major teaching hospitals. Among children's hospitals, major teaching hospitals were significantly more likely to have an EHR., Conclusions: Children's hospitals have achieved substantial gains in HIT implementation although minor teaching and nonteaching institutions are not keeping pace.

Importance: Readmission rates are used as an indicator of the quality of care that patients receive during a hospital admission and after discharge., Objective: To determine the prevalence of pediatric readmissions and the magnitude of variation in pediatric readmission rates across hospitals., Design, Setting, and Patients: We analyzed 568,845 admissions at 72 children's hospitals between July 1, 2009, and June 30, 2010, in the National Association of Children's Hospitals and Related Institutions Case Mix Comparative data set. We estimated hierarchical regression models for 30-day readmission rates by hospital, accounting for age and Chronic Condition Indicators. Hospitals with adjusted readmission rates that were 1 SD above and below the mean were defined as having "high" and "low" rates, respectively., Main Outcome Measures: Thirty-day unplanned readmissions following admission for any diagnosis and for the 10 admission diagnoses with the highest readmission prevalence. Planned readmissions were identified with procedure codes from the International Classification of Diseases, Ninth Revision, Clinical Modification., Results: The 30-day unadjusted readmission rate for all hospitalized children was 6.5% (n = 36,734). Adjusted rates were 28.6% greater in hospitals with high vs low readmission rates (7.2% [95% CI, 7.1%-7.2%] vs 5.6% [95% CI, 5.6%-5.6%]). For the 10 admission diagnoses with the highest readmission prevalence, the adjusted rates were 17.0% to 66.0% greater in hospitals with high vs low readmission rates. For example, sickle cell rates were 20.1% (95% CI, 20.0%-20.3%) vs 12.7% (95% CI, 12.6%-12.8%) in high vs low hospitals, respectively., Conclusions and Relevance: Among patients admitted to acute care pediatric hospitals, the rate of unplanned readmissions at 30 days was 6.5%. There was significant variability in readmission rates across conditions and hospitals. These data may be useful for hospitals' quality improvement efforts.

Policy-makers increasingly rely on cost-effectiveness analysis, in addition to clinical effectiveness, when considering the introduction of new childhood vaccines. A previous analysis determined vaccination of infants with 7-valent pneumococcal conjugate vaccine (PCV) to be highly cost effective in preventing child mortality in countries eligible for financial support from the Global Alliance for Vaccines and Immunization (GAVI). We aimed to update this analysis by incorporating recent data on global disease burden, indirect effects and higher valency vaccines. Decision analytic models were built using an incidence-based approach in order to evaluate a three-dose vaccination schedule of infants in 72 GAVI-eligible countries over a 10-year programme. Seven-, 10- and 13-valent vaccine formulations were each compared with no vaccination. Depending on the formulation used, PCV could avert 294 000-603 000 deaths and 9.3-17.6 million disability-adjusted life-years (DALY) annually. The majority (91%) of the DALYs averted would be through the vaccine's direct effects in children under-5. Using WHO thresholds and a negotiated average dose cost, PCV would be highly cost effective in 69 of 72 GAVI-eligible countries. This finding was robust when assumptions regarding disease epidemiology and vaccine-related effects were varied in sensitivity analyses. The current analysis supports PCV introduction in GAVI-eligible countries owing to its potential to avert substantial numbers of deaths at relatively low incremental costs.

Policy-makers require information on the potential benefits of and economic case for pneumococcal conjugate vaccination in middle-income countries. We built decision analysis models to evaluate a three-dose infant series of the 7-, 10- or 13-valent pneumococcal conjugate vaccines in 77 middle-income countries compared with no vaccination, accounting for direct protection of vaccinated children as well as herd protection and serotype replacement in unvaccinated children and adults. Over 10 years, pneumococcal vaccination would prevent at least 11.0 million cases and 314 000 deaths in children under-5, one-third of the pneumonia and invasive disease cases and deaths that would occur in this age group without vaccination. Herd protection would prevent 3.1 million cases and 163 000 deaths in older children and adults. A total of 11.1 million discounted disability-adjusted life-years (DALY) would be averted. At a dose cost of $10 for lower- middle-income and $20 for upper-middle-income countries, the net pooled (for all countries together) discounted vaccination cost would be $18.1 billion ($1600 per DALY averted). Vaccination would be cost effective for 72 countries with the 7-valent vaccine and for all countries with the 10- or 13-valent vaccines. The economic case for vaccination is compelling for middle-income countries.

Objective: To assess adoption of electronic health records (EHRs) and clinical functionalities, involvement in health information exchange, and barriers to and facilitators of adoption among children's hospitals in the United States., Design: Survey presented as an information technology supplement to the American Hospital Association's annual member survey., Setting: General acute care children's hospitals in 2008, identified using the membership directory of the National Association of Children's Hospitals and Related Institutions., Participants: Chief information officers or equivalent hospital leaders., Main Exposures: Potential barriers to or facilitators of EHR adoption., Main Outcome Measures: Rates of EHR adoption, determined using expert-formulated definitions based on presence of essential functionalities, and rates of implementation for individual functionalities and participation in health information exchange., Results: Of 155 children's hospitals, 108 (69.7%) responded to the survey. Only 2.8% had a comprehensive EHR, whereas an additional 17.9% had a basic system. Adoption of individual functionalities varied widely; comprehensive implementations of computerized provider order entry for medications and many forms of decision support were reported by fewer than half. In all, 15.7% of hospitals exchanged health information electronically. Hospital characteristics were not associated with EHR adoption or participation in health information exchange. Hospitals identified financing as the most important target for policy strategies., Conclusions: Most children's hospitals lack the minimum functionalities needed for a basic EHR. Ensuring access to adequate financial resources will be critical for inclusion of children's hospitals in efforts to expand EHR use.

Sensitive detection of Staphylococcus aureus colonization is important for epidemiologic studies, infection control, and decolonization measures. We examined the sensitivity of nasal and pharyngeal sampling for S. aureus colonization in 331 children admitted to intensive care units. Pharyngeal screening was more sensitive than nasal screening (92.6% versus 63.1%, P < 0.0001).

Objectives: We assessed influenza vaccination rates from 1992 to 2002, individual continuity of vaccination, and missed opportunities for vaccination in adolescents with high-risk conditions., Methods: We performed a retrospective observational study of 18 703 adolescents with high-risk conditions who were enrolled in a large health maintenance organization and received care at a multisite practice for >or=1 influenza season and the preceding year, between 1992 and 2002, was performed. Subjects were identified as having a high-risk condition if they had >or=1 visit with an associated International Classification of Diseases, Ninth Revision, Clinical Modification code during the season or previous year. Influenza vaccination rates were compared by season in logistic regression analyses, using generalized estimating equations for repeated measurements of subjects enrolled for multiple seasons. Vaccination continuity was measured for adolescents who were enrolled for 4 consecutive seasons (1999-2002) as the number of seasons during which vaccine was received. Missed opportunities were defined as visits during the first 4 months of influenza season at which an unvaccinated adolescent did not receive vaccine., Results: For adolescents with high-risk conditions, influenza vaccination rates varied from 8.3% to 15.4%. Rates improved significantly from 1992 to 1993, from 8.3% to 12.8%, and again in 2001, reaching 15.4%. Only 11.1% of those enrolled continuously from 1999 to 2002 received vaccine during all 4 seasons. According to season from 1992 to 2002, 45.7% to 53.6% of unvaccinated subjects had >or=1 missed opportunity., Conclusions: Influenza vaccination rates in adolescents with high-risk conditions improved from 1992 to 2002 but were still low in recent years. Individual vaccination continuity was poor. Numerous opportunities already exist for improving coverage.

Mammalian genomes contain numerous evolutionary harbored mobile elements, a part of which are still active and may cause genomic instability. Their movement and positional diversity occasionally result in phenotypic changes and variation by causing altered expression or disruption of neighboring host genes. Here, we describe a novel microarray-based method by which dispersed genomic locations of a type of retrotransposon in a mammalian genome can be identified. Using this method, we mapped the DNA elements for a mouse retrotransposon, intracisternal A-particle (IAP), within genomes of C3H/He and C57BL/6J inbred mouse strains; consequently we detected hundreds of probable IAP cDNA-integrated genomic regions, in which a considerable number of strain-specific putative insertions were included. In addition, by comparing genomic DNAs from radiation-induced myeloid leukemia cells and its reference normal tissue, we detected three genomic regions around which an IAP element was integrated. These results demonstrate the first successful genome-wide mapping of a retrotransposon type in a mammalian genome.

Radiation-induced thymic lymphoma in mice is a useful model for studying both the mechanism of radiation carcinogenesis and genetic susceptibility to tumor development. Using array-comparative genomic hybridization, we analyzed genome-wide changes in DNA copy numbers in radiation-induced thymic lymphomas that had developed in susceptible C57BL/6 and resistant C3H mice and their hybrids, C3B6F1 and B6C3F1 mice. Besides aberrations at known relevant genetic loci including Ikaros and Bcl11b and trisomy of chromosome 15, we identified strain-associated genomic imbalances on chromosomes 5, 10 and 16 and strain-unassociated trisomy of chromosome 14 as frequent aberrations. In addition, biallelic rearrangements at Tcrb were detected more frequently in tumors from C57BL/6 mice than in those from C3H mice, suggesting aberrant V(D)J recombination and a possible link with tumor susceptibility. The frequency and spectrum of these copy-number changes in lymphomas from C3B6F1 and B6C3F1 mice were similar to those in C57BL/6 mice. Furthermore, the loss of heterozygosity analyses of tumors in F(1) mice indicated that allelic losses at Ikaros and Bcl11b were caused primarily by multilocus deletions, whereas those at the Cdkn2a/Cdkn2b and Pten loci were due mainly to uniparental disomy. These findings provide important clues to both the mechanisms for accumulation of aberrations during radiation-induced lymphomagenesis and the different susceptibilities of C57BL/6 and C3H mice.

We integrate a personally-controlled health record (PCHR) with a Department of Public Health (DPH) immunization registry and clinical decision support (CDS) tool, creating an immunization information system using a service-oriented architecture (SOA). This SOA enables the DPH, a trusted authority, to provide CDS to both clinicians and patients/parents.

To survive in a host environment, microbial pathogens must sense local conditions, including nutrient availability, and adjust their growth state and virulence functions accordingly. No comprehensive investigation of growth phase-related gene regulation in Bordetella pertussis has been reported previously. We characterized changes in genome-wide transcript abundance of B. pertussis as a function of growth phase and availability of glutamate, a key nutrient for this organism. Using a Bordetella DNA microarray, we discovered significant changes in transcript abundance for 861 array elements during the transition from log phase to stationary phase, including declining transcript levels of many virulence factor genes. The responses to glutamate depletion exhibited similarities to the responses induced by exit from log phase, including decreased virulence factor transcript levels. However, only 23% of array elements that showed at least a fourfold growth phase-associated difference in transcript abundance also exhibited glutamate depletion-associated changes, suggesting that nutrient limitation may be one of several interacting factors affecting gene regulation during stationary phase. Transcript abundance patterns of a Bvg+ phase-locked mutant revealed that the BvgAS two-component regulatory system is a key determinant of growth phase- and nutrient limitation-related transcriptional control. Several adhesin genes exhibited lower transcript abundance during stationary phase and under glutamate restriction conditions. The predicted bacterial phenotype was confirmed: adherence to bronchoepithelial cells decreased 3.3- and 4.4-fold at stationary phase and with glutamate deprivation, respectively. Growth phase and nutrient availability may serve as cues by which B. pertussis regulates virulence according to the stage of infection or the location within the human airway.

Background: Reports from various geographic regions indicate that the prevalence of community-acquired methicillin-resistant (MRSA) infection is increasing. The primary reservoir is the anterior nares; nasal carriage is a risk factor for infection in a variety of populations. Little is known about MRSA nasal carriage rates among children in Nashville, TN and the associated likelihood of community MRSA transmission., Methods: Nasal swabs were collected from 500 children at well-child visits at either a university hospital pediatric clinic or a private pediatric office. Cultures were plated onto selective staphylococcal media, with or without oxacillin. isolates were confirmed by coagulase tube testing. Antibiotic susceptibilities were determined for suspected methicillin-resistant isolates by standard broth microdilution methods (National Committee for Clinical Laboratory Standards). Pulsed field gel electrophoresis was used to evaluate epidemiologic relatedness. PCR testing was done to assess for the gene. A parent questionnaire was administered regarding MRSA risk factors., Results: Four patients had oxacillin-resistant isolates (MIC >or= 4 microg/ml), and two had borderline resistant isolates (MICs = 1 and 2 microg/ml). One of the borderline-resistant isolates and one of the MRSA isolates had pulsed field gel electrophoresis typing results indicating close relatedness. The gene was present in all resistant isolates and one of the borderline-resistant isolates. Only having a household member employed in a hospital was associated with a greater risk of MRSA nasal carriage (odds ratio, 9.6; P= 0.008)., Conclusions: MRSA nasal colonization is present within Nashville's healthy pediatric population. Children with household contacts employed in a hospital are significantly more likely to be colonized.