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Objectives: To determine the effect of early conversion to oral antibiotics in infants ≤90 days with gram-negative bacteremia and concomitant urinary tract infection on hospital length of stay (LOS) and 30-day revisits for urinary tract infection., Design: This retrospective cohort study included infants ≤ 90 days who had concomitant positive blood and urine cultures with gram-negative bacteremia at 22 hospitals from January 1, 2002 through January 31, 2020. Early oral conversion was defined as a maximum intravenous (IV) duration of 4 days. We conducted a noninferiority test to compare early oral conversion to long IV therapy. A propensity score framework was used to assess comparisons in survey-weighted regression models using matched weights., Results: Among 174 infants, 73 infants received early oral conversion. The LOS was shorter in infants receiving early oral conversion compared to long IV therapy (median 2 days [interquartile range 2, 3] vs 4 days [3, 5]), descriptively (P < .001) and in noninferiority analysis (ratio = 0.43; 90% CI 0.35, 0.53, P < .001). Thirty-day revisits occurred in 5 of 174 (2.8%) of total patients. Early oral conversion did not meet our noninferiority criteria for the 30-day revisits (odds ratio: 4.22, 90%; confidence interval: 0.83, 21.34, P = .91)., Conclusions: Early oral conversion was associated with shorter LOS. The rate of 30-day revisit rates overall was low., (Copyright © 2022 by the American Academy of Pediatrics.)

Background and Objectives: Researchers in previous studies suggest that the clinical yield of follow-up blood cultures (FUBCs) is low in infants with bacteremic urinary tract infection (UTI) because persistent bacteremia is rare; however, no researchers have analyzed the practice of routinely obtaining FUBCs. In our study, we evaluate outcomes in infants with FUBCs, examine opportunities for improvement of blood culture practices, and add important information to inform both clinical practice as well as further study., Design: This retrospective cohort study included infants <90 days of age with bacteremia and UTI with the same pathogen at 22 hospitals that make up Intermountain Healthcare between 2002 to 2020. Infants with culture proven meningitis, osteomyelitis, central line infection, and infections occurring during NICU hospitalization were excluded., Results: Total number of patients with bacteremic UTI was 174, 153 (88%) patients had at least 1 FUBC, 14 of 153 (9%) had a positive FUBC with same organism, and 4 of 153 (3%) were contaminants. The length of stay was longer for patients with positive FUBCs. Patients with Escherichia coli are more likely to have a negative FUBC. Readmissions within 30 days were similar among infants with positive FUBCs, negative FUBCs, and no FUBCs., Conclusions: FUBCs in infants with bacteremic UTI should not be routinely performed, especially for E coli, and it is unclear whether FUBCs improve outcomes., Competing Interests: FINANCIAL DISCLOSURES: The authors have indicated they have no financial relationships relevant to this article to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

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 febrile neutropenia (FN) is a frequent complication in children with cancer receiving chemotherapy, there remains significant variability in selection of route (intravenous [IV] vs oral) and length of therapy. We implemented a guideline with a goal to change practice from using IV antibiotics after hospital discharge to the use of step-down oral therapy with levofloxacin for most children with FN until absolute neutrophil count > 500. The objectives of this study were to determine the impact of this guideline on home IV antibiotic use, and to evaluate the safety of implementation of this guideline., Methods: We performed a quasi-experimental, pre-post study of discharge FN treatment at a stand-alone children's hospital in patients without bacteremia discharged between January 2013 and October 2018. In January 2015, a multidisciplinary team created a guideline to switch most children with FN to oral levofloxacin, which was formally implemented as of September 2017. Discharges during the postintervention period (after September 2017) were compared to discharges in the preintervention period (between January 2013 and December 2014)., Results: In adjusted multivariable regression analyses, the postimplementation period was associated with a decrease in home IV antibiotics (adjusted risk ratio [aRR], 0.07 [95% confidence interval {CI}, .03-.13]) and fewer IV antibiotic initiations within 24 hours of a new healthcare encounter up to 7 days after discharge (aRR, 0.39 [95% CI, .17-.93]) compared to the preintervention time period., Conclusions: Step-down oral levofloxacin for children with FN who are afebrile with an ANC ≤ 500 at discharge is feasible and resulted in similar clinical outcomes compared to home IV antibiotics., (© 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.)

Background: Vancomycin optimization is challenging, requiring careful therapeutic drug monitoring (TDM) to avoid toxicity and ensure an efficacious concentration. Most prescriptions are empiric and often discontinued within 72 hours, which makes early TDM unnecessary. Although TDM using trough levels is common, the area under the concentration-time curve (AUC) is the preferred pharmacodynamic target. We studied the effect of a pharmacy-driven vancomycin collaborative practice agreement (CPA) at a children's hospital that delayed TDM up to 72 hours and targeted a 2-point 24-hour AUC of ≥400 mg × h/L., Methods: We retrospectively reviewed vancomycin courses in patients aged ≥30 days who received vancomycin between April 1, 2011, and August 30, 2017. We implemented the CPA on June 1, 2014. Outcomes included CPA use, use of TDM, dosage adjustments, and development of acute kidney injury; we compared courses given while monitoring only trough levels (TO-TDM) with those given while using the CPA (AUC-TDM). We performed interrupted time series analyses to account for preintervention trends., Results: We included 2379 courses in the TO-TDM period and 2155 in the AUC-TDM period. During AUC-TDM, 87% of the courses were managed by the CPA. In adjusted interrupted time series analyses, CPA implementation was associated with an initial change in level of -0.265 (95% confidence interval [CI], -0.336 to -0.189) TDM and an initial change in level of -0.332 (95% CI, -0.506 to -0.163) dosage adjustments. The 1-year risk of acute kidney injury decreased after CPA implementation (odds ratio, 0.695 [95% CI, 0.539-0.91])., Conclusion: The pharmacy-driven vancomycin CPA resulted in less monitoring and fewer dose adjustments without increasing AKI., (© The Author(s) 2019. 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 Objectives: National guidelines advocate for the administration of antibiotics within 1 hour to children with septic shock, although there is variance in the pediatric evidence-based literature supporting this benchmark. Our objective for this study was to describe the association of target time to antibiotic administration (TTAA) with outcomes of children treated for suspected septic shock in a pediatric emergency department. Septic shock is suspected when signs of perfusion and/or hypotension are present. The primary outcome was mortality. Secondary outcomes included PICU admission, hospital and PICU length of stay, and organ dysfunction resolution by hospital day 2., Methods: We conducted a retrospective study of children <18 years of age admitted from the pediatric emergency department and treated for suspected septic shock between February 1, 2007, and December 31, 2015. Associations between TTAA and outcomes were evaluated by using multivariable linear and logistic regression models obtained from stepwise selection., Results: Of 1377 patients, 47% were boys with a median age of 4.0 (interquartile range 1.4-11.6) years, 1.5% (20) died, 90% were compliant with TTAA goals, 40% required PICU admission, 38% had ≥2 unique complex chronic conditions, 71% received antibiotics in ≤2 hours, and 30% had a culture-positive bacterial etiology. There were no significant associations between TTAA and outcomes., Conclusions: We found no association with TTAA and any clinical outcomes, adding to the growing body of literature questioning the timing benchmark of antibiotic administration. Although the importance of antibiotics is not in question, elucidating the target TTAA may improve resource use and decrease inappropriate or unnecessary antibiotic exposure., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

We conducted a retrospective study to evaluate suboptimal discharge antibiotic prescribing at a children's hospital and found that 27% of the prescriptions were suboptimal. Thirty-three percent of the patients who might have qualified for solid dosage forms received liquid dosages instead. Our findings suggest that opportunities exist for discharge antibiotic-stewardship and pill-swallowing programs., (© The Author(s) 2018. 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.)

Objective: Review the evaluation of children with a deep lateral neck infection and define the impact of initial imaging modality on outcomes and costs., Method: Case series, pediatric patients <18 years of age admitted to a tertiary care hospital with lateral neck infection between 01/01/14-05/31/16 as identified by ICD-9 and ICD-10 codes: 289.3 (lymphadenitis, unspecified), 682.1 (cellulitis and abscess of neck), 683 (acute lymphadenitis), I88.9 (nonspecific lymphadenitis, unspecified), L02.11 (cutaneous abscess of neck), L03.221 (cellulitis of neck), and L03.222 (acute lymphangitis of neck). Patients were divided into two groups based on initial imaging modality: primary ultrasound or primary computed tomography. Differences in length of stay, type and total number of imaging studies obtained, number of procedures, hospital readmission, and hospital cost were compared between cohorts., Results: There were 40 (31%) primary ultrasound and 88 (69%) primary computed tomography patients (128 total). Median length of stay was 46 (IQR: 25,90) hours (1.9 days) for primary ultrasound and 63 (IQR: 39,88) hours (2.6 days) for primary computed tomography patients (p = 0.33). Drainage was performed in 48% of both groups. Additional imaging occurred in 17 (43%) primary ultrasound and 18 (20%) primary computed tomography patients (p = 0.02). Readmission occurred in 8 patients (6.3%). Retropharyngeal infection was encountered in 13 patients (10%); this was only discovered in patients who had a computed tomography performed. Median cost per primary ultrasound patients was $5363 (IQR: 3011, 7920) and $5992 (IQR: 3450, 8060) for primary computed tomography patients., Conclusions: The primary imaging modality (ultrasound or computed tomography) used to work-up children with a lateral neck infection did not impact length of stay or hospital cost. However, a significant subset had a coexisting retropharyngeal infection that was only identified on computed tomography. Future studies are needed to identify appropriate criteria for imaging in the work-up of lateral neck infections., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We developed an outpatient parenteral antibiotic therapy (OPAT) stewardship program in a freestanding children's hospital to improve the appropriateness of OPAT prescribing. Introduction of the program enabled expert review of nearly 90% of the patients being prepared for discharge with OPAT and was associated with a 24% reduction in OPAT use.

We examined clinical outcomes for 53 young infants (<3 months of age) treated with outpatient parenteral antimicrobial therapy after discharge from a freestanding children's hospital. None of the patients experienced treatment failure or disease progression; 9% of them experienced a catheter-related complication, but this percentage is not different than that for older children.

Background: Febrile infants with viral respiratory infections have a reduced risk of bacterial infection compared with virus-negative infants. The risk of concomitant bacterial infection in febrile infants positive for human rhinovirus (HRV) by polymerase chain reaction (PCR) is unknown., Methods: Infants 1-90 days old managed using the care process model for well-appearing febrile infants and with respiratory viral testing by PCR (RVPCR) in the emergency department or inpatient setting of 22 hospitals in the Intermountain Healthcare system from 2007-2016 were identified. Relative risk (RR) of bacterial infection was calculated for infants with HRV, non-HRV viruses, or no virus detected., Results: Of 10 964 febrile infants identified, 4037 (37%) had RVPCR. Of these, 2212 (55%) were positive for a respiratory virus; 1392 (35%) for HRV alone. Bacterial infection was identified in 9.5%. Febrile infants with HRV detected were more likely to have bacterial infection than those with non-HRV viruses (7.8% vs 3.7%; P < .001; RR 2.12 [95% CI 1.43-3.15]). Risk of urinary tract infection was not significantly different for HRV-positive infants at any age, nor was risk of invasive bacterial infection (IBI; bacteremia and/or meningitis) meaningfully different for infants 1-28 day olds. Infants 29-90 days old with HRV had a decreased likelihood of IBI (RR 0.52 [95% CI 0.34-0.80])., Conclusions: HRV is common in febrile infants. Detection did not alter risk of concomitant urinary tract infection at any age or risk of IBI in infants 1-28 days old. HRV detection may be relevant in considering risk of IBI for infants 29-90 days of age., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Drs Blaschke and Byington have intellectual property and receive royalties from BioFire Diagnostics LLC through the University of Utah; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Objective: To evaluate the risk of nonsteroidal anti-inflammatory drug (NSAID) therapy-associated acute kidney injury (AKI) among neonates diagnosed with patent ductus arteriosus (PDA) who are treated with gentamicin., Study Design: Multicenter retrospective observational study of patients ⩽44 postmenstrual weeks of age diagnosed with PDA who received gentamicin during hospitalization between January 2006 and December 2014. Patients with and without NSAID exposure were matched on covariates associated with AKI and NSAID therapy. The primary end point, AKI, was defined according to Kidney Disease Improving Global Outcomes neonatal criteria., Results: The rate of AKI for the entire cohort (n=594) was 12% (n=71). Among neonates receiving NSAIDS, 14.8% (n=44) experienced an AKI as compared to 9.1% (n=27) for those who were not exposed (relative risk, 1.6; 95% confidence interval, 1.0 to 2.6). Therefore, the attributable risk of NSAID use was 5.7% (95% confidence interval, 0.5 to 11.0)., Conclusion: Among neonates with PDA and receiving gentamicin, NSAID therapy increases the risk of AKI by about 6%.

Objectives: To evaluate whether a quality improvement intervention reduces sternal wound infection rates in children after cardiac surgery., Design: This is a pre- and postintervention quality improvement study., Setting: A 16-bed cardiac ICU in a university-affiliated pediatric tertiary care children's hospital., Patients: All patients undergoing cardiac surgery via median sternotomy from January 2010 to December 2014 are included. The sternal wound infection rates for primary closure and delayed sternal closure are reported per 100 sternotomies. The hospital-acquired infection records were used to identify preintervention cases, while postintervention cases were collected prospectively., Intervention: Implementation of a sternal wound prevention bundle during the preoperative, intraoperative, and postoperative periods for cardiac surgical cases., Measurements and Main Results: During the preintervention period, 32 patients (3.8%) developed sternal wound infection, whereas only 19 (2.1%) developed sternal wound infection during the postintervention period (p = 0.04). The rates of sternal wound infection following primary closure were not significantly different pre- and postintervention (2.4% vs 1.6%; p = 0.35). However, patients with delayed sternal closure had significantly lower postintervention infection rates (10.6% vs 3.9%; p = 0.02)., Conclusions: Implementation of a sternal wound prevention bundle during the perioperative period was associated with lower sternal wound infection rates in surgeries with delayed sternal closure.

Introduction: Rapid identification of bloodstream pathogens provides crucial information that can improve the choice of antimicrobial therapy for children. Previous impact studies have primarily focused on adults. Our objective was to evaluate the impact of rapid testing in a children's hospital on time to organism identification and antibiotic use in the setting of an established antimicrobial stewardship program., Methods: We conducted a retrospective study over three consecutive time periods (spanning January 2013-August 2015) as our hospital sequentially introduced two rapid testing methods for positive blood cultures. An antimicrobial stewardship program was active throughout the study. In the baseline period, no rapid diagnostic methods were routinely utilized. In the second period (PNAFISH), a fluorescent in situ hybridization test was implemented for gram-positive organisms and in the third a rapid multiplex PCR (rmPCR) test was employed. For children with positive blood cultures, time to organism identification use and duration of select antimicrobial therapies were compared between periods., Results: Positive blood cultures were analyzed. Median overall time to organism identification was 23, 11, and 0 h in the baseline, PNAFISH, and rmPCR periods, respectively (p < 0.001 for both PNAFISH and rmPCR vs. baseline). For gram-negative organisms, only rmPCR performed significantly faster than baseline (p < 0.001). The duration of vancomycin use for coagulase-negative staphylococci was shorter in both the PNAFISH and rmPCR periods (mean 31 h in the baseline period, 12 and 14 h in the PNAFISH and rmPCR periods, respectively). For MSSA bacteremia, use of vancomycin was significantly decreased only in the rmPCR period (32% of patients vs. 64 and 72% in the baseline and PNAFISH periods; mean duration of 9 h vs. 30 and 26 h). There was no difference in use or duration of broad-spectrum gram-negative therapy across the three time periods., Conclusion: Rapid diagnostic testing for children with positive blood cultures results in faster time to identification and can influence antibiotic prescribing in the setting of active antimicrobial stewardship particularly for gram-positive pathogens., Funding: Merck.

Background: Human metapneumovirus (HMPV) causes acute respiratory tract infections in infants and children. We sought to measure the clinical and economic burden of HMPV infection in hospitalized children., Methods: We conducted a retrospective cohort study from 2007 to 2013 at Primary Children's Hospital in Salt Lake City, Utah. Children <18 years of age with laboratory-confirmed HMPV infection were included. Demographic, clinical, and financial data were abstracted from the electronic medical record., Results: During the study period, 815 children were hospitalized with laboratory-confirmed HMPV infection: 16% <6 months, 50% 6-23 months, 23% 2-4 years, and 11% 5-17 years of age. A complex chronic condition was identified in 453 (56%) children hospitalized with HMPV infection; this proportion increased with increasing age (P < .001). There was marked variation in annual HMPV hospitalization rates, ranging from 9 of 100 000 person-years in 2012-2013 to 79 of 100 000 in 2009-2010. Hospitalization rates were highest among children <2 years (200 of 100 000 person-years) and lowest among children 5-17 years of age (5 of 100 000). Of hospitalized children, 18% were treated in the intensive care unit and 6% required mechanical ventilation. The median length of stay was 2.8 days (interquartile range [IQR], 1.8-4.6) and did not vary by age. The median total hospital cost per patient was $5513 (IQR, $3850-$9946) with significantly higher costs for patients with chronic medical conditions (P < .001)., Conclusions: Human metapneumovirus infection results in a large number of hospitalizations with substantial morbidity, resource utilization, and costs. The development of a safe and effective vaccine could reduce the clinical and economic burden of HMPV., (© The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections (IFI), including aspergillosis, candidiasis, Scedosporium infection, and Fusarium infection. IFI often occur in immunocompromised patients, leading to increased morbidity and mortality., Areas Covered: The objective of this review is to summarize the pharmacodynamic properties of voriconazole and to provide considerations for potential optimal dosing strategies. Studies have demonstrated superior clinical response when an AUC/MIC >25 or Cmin/MIC >1 is attained in adult patients, correlating to a trough concentration range as narrow as 2-4.5 mg/L; however, these targets are poorly established in the pediatric population. Topics in this discussion include voriconazole use in multiple age groups, predisposing patient factors for IFI, and considerations for clinicians managing IFI. Expert commentary: The relationship between voriconazole dosing and exposure is not well defined due to the large inter- and intra-subject variability. Development of comprehensive decision support tools for individualizing dosing, particularly in children who require higher dosing, will help to increase the probability of achieving therapeutic efficacy and decrease sub-therapeutic dosing and adverse events.

Background: Rapid multiplex polymerase chain reaction (PCR) assays simultaneously detect several respiratory viral pathogens with high sensitivity. Maximizing detection of influenza at the point of care has the potential to reduce unnecessary antibiotic use, laboratory tests and hospitalizations. However, the cost-effectiveness of rapid multiplex PCR assays for influenza has not been compared with other diagnostic methods in children., Methods: For children presenting to the emergency department with influenza-like illness, we compared costs and outcomes using 4 different testing strategies for detection of influenza: (1) a rapid multiplex PCR platform (FilmArray); (2) traditional PCR; (3) direct-fluorescent antibody and (4) rapid antigen tests. Costs were assessed from the hospital perspective, and effectiveness was defined as quality-adjusted life years (QALYs). Input parameters were obtained from previous studies, and the model was run separately for children aged 3-36 months and 3-18 years., Results: Rapid multiplex PCR testing was the most effective testing strategy for children in both age groups. The incremental cost-effectiveness when compared with rapid antigen tests was $115,556 per QALY for children aged 3-36 months and from $228,000 per QALY for children aged 3-18 years. The cost-effectiveness of rapid multiplex PCR was sensitive to estimates for influenza prevalence, the proportion of patients treated with antivirals and the cost per test., Conclusions: Our model identifies scenarios in which identification of influenza in the emergency department using rapid multiplex PCR testing is a cost-effective strategy for infants and children 3 months through 18 years. Including detection of other respiratory viruses in the analysis would further improve cost-effectiveness.

We surveyed hospital epidemiologists at 28 Children's Hospital Association member hospitals regarding their infection prevention and control programs. We found substantial variability between children's hospitals in both the structure and the practice of these programs. Research and the development of evidence-based guidelines addressing infection prevention in pediatrics are needed.

Objective: Document information needs, gaps within the current electronic applications and reports, and workflow interruptions requiring manual information searches that decreased the ability of our antimicrobial stewardship program (ASP) at Intermountain Healthcare (IH) to prospectively audit and provide feedback to clinicians to improve antimicrobial use., Methods: A framework was used to provide access to patient information contained in the electronic medical record, the enterprise-wide data warehouse, the data-driven alert file and the enterprise-wide encounter file to generate alerts and reports via pagers, emails and through the Centers for Diseases and Control's National Healthcare Surveillance Network., Results: Four new applications were developed and used by ASPs at Intermountain Medical Center (IMC) and Primary Children's Hospital (PCH) based on the design and input from the pharmacists and infectious diseases physicians and the new Center for Diseases Control and Prevention/National Healthcare Safety Network (NHSN) antibiotic utilization specifications. Data from IMC and PCH now show a general decrease in the use of drugs initially targeted by the ASP at both facilities., Conclusions: To be effective, ASPs need an enormous amount of "timely" information. Members of the ASP at IH report these new applications help them improve antibiotic use by allowing efficient, timely review and effective prioritization of patients receiving antimicrobials in order to optimize patient care.

We reviewed patient discharges with outpatient parenteral antimicrobial therapy (OPAT) to determine whether outpatient parenteral antimicrobial therapy was modifiable or unnecessary at a large tertiary care children's hospital. At least one modification definitely or possibly would have been recommended for 78% of episodes. For more than 40% of episodes, outpatient parenteral antimicrobial therapy was potentially not indicated.

Monitoring of vancomycin trough concentrations is recommended for pediatric patients in the product label and by several professional societies. However, among a network of freestanding children's hospitals vancomycin therapeutic drug monitoring (TDM) practices were reported to be highly variable. In this study, we sought to evaluate whether trends in vancomycin use and TDM changed across a large healthcare delivery system in Utah and Idaho from 2006 to 2012. Children ≤18 years who received ≥2 vancomycin doses were included. Overall, vancomycin TDM was performed during 5,035 (80%) of 6,259 hospital encounters, in which 85,442 doses were administered and 7,935 concentrations were obtained. Across this time period, the median trough concentration increased from 10.9 to 13.7 µg/mL (P < .001), which temporally coincided with recommendations published by the Infectious Disease Society of America that recommend targeting higher trough concentrations. Two or more abnormally low trough concentrations were accompanied by an increase in the dose 75% of the time. Similarly, ≥2 abnormally high trough concentrations were followed by a decrease in the dose 35% of the time. In aggregate, these data suggest that vancomycin TDM is commonly performed among children and the majority of abnormal trough concentrations were associated with an appropriate modification to the dosing regimen., (© 2014, The American College of Clinical Pharmacology.)

Purpose: Postoperative management of pediatric patients with non-ruptured appendicitis is highly variable and often includes an overnight stay in the hospital. We implemented a criteria-based postoperative protocol designed to eliminate postoperative antibiotics and facilitate timely discharge by utilizing the bedside nurse to evaluate for readiness for discharge., Methods: We collected data on all patients with non-ruptured appendicitis at our institution following protocol implementation (May 1, 2012 to April 30, 2013) and compared them to a control group., Results: 580 patients were treated for non-ruptured appendicitis (285 prior protocol, 295 new protocol). Following implementation of our protocol, there was an overall reduction in length of stay from 40.1 (SD 27.5) to 23.5 (SD 20.8)h, and total cost of care per patient also decreased from $5783 (SD $2501) to $4499 (SD $1983) (p<0.001). There was no change in hospital readmission rate (1.1% prior protocol, 1.4% new protocol) or postoperative abscess rate (0.8% prior protocol, 0.3% new protocol)., Conclusion: Our new protocol reveals the value of eliminating postoperative antibiotics and leveraging the continuous availability of the bedside nurse in the determination of readiness for discharge., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We examined the effectiveness of a postoperative ruptured appendicitis protocol that eliminated Pseudomonas coverage and based the duration of IV antibiotic treatment and length of hospital stay on the patient's clinical response., Methods: In our new protocol, IV antibiotics were administered until the patient met discharge criteria: adequate oral intake, pain control with oral medications, and afebrile for 24h. We collected data on all patients with ruptured appendicitis at our institution following protocol implementation (May 1, 2012, to April 30, 2013) and compared them to a control group., Results: 306 patients were treated (154 prior protocol, 152 new protocol). The new clinical response-based protocol led to a decrease in hospital stay from 134h (SD 66.1) to 94.5h (SD 61.7) (p<0.001) and total cost of care per patient also decreased from $13,610 (SD $6859) to $9870 (SD $5670) (p<0.001)., Conclusion: Our clinical response-based protocol for pediatric patients with ruptured appendicitis decreased LOS, cost, and IV antibiotics use without significant changes in adverse events., (Copyright © 2014. Published by Elsevier Inc.)

Background: The relationship between first and subsequent cerebrospinal fluid (CSF) shunt infections is poorly understood. By understanding the factors associated with increased risk of reinfection, researchers may provide optimal treatment strategies at the time of first infection. The objective of this study was to describe and compare children with and without CSF shunt reinfection., Methods: A retrospective cohort study was performed among 118 children who underwent initial CSF shunt placement and developed first CSF shunt infection. The primary outcome variable was CSF shunt reinfection. Patient risk factors and medical and surgical management of initial CSF shunt placement and first CSF shunt infection were compared between children with and without reinfection., Results: Of 118 children with first infection, 31 (26%) developed a reinfection during the study period (overall median follow-up, 2096 days). Factors associated with reinfection in this cohort included ventriculoatrial or complex shunt at initial CSF shunt placement, complications after first CSF shunt infection, and intermittent negative CSF cultures., Conclusions: Few patient or treatment factors were associated with reinfection. Factors associated with difficult-to-treat first CSF shunt infection, including complications after first CSF shunt infection and intermittent negative CSF cultures, were associated with reinfection. Clinicians who treat patients with unusual CSF shunts or more difficult first infections should have a high index of suspicion for reinfection after treatment is completed., (© The Author 2013. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The management of neonatal sepsis is challenging owing to complex developmental and environmental factors that contribute to inter-individual variability in the pharmacokinetics and pharmacodynamics of many antimicrobial agents. In this review, we describe (i) the changing epidemiology of early- and late-onset neonatal sepsis; (ii) the pharmacologic considerations that influence the safety and efficacy of antibacterials, antifungals, and immunomodulatory adjuvants; and (iii) the recommended dosing regimens for pharmacologic agents commonly used in the treatment and prevention of neonatal sepsis. Neonatal sepsis is marked by high morbidity and mortality, such that prompt initiation of antimicrobial therapy is essential following culture collection. Before culture results are available, combination therapy with ampicillin and an aminoglycoside is recommended. When meningitis is suspected, ampicillin and cefotaxime may be considered. Following identification of the causative organism and in vitro susceptibility testing, antimicrobial therapy may be narrowed to provide targeted coverage. Therapeutic drug monitoring should be considered for neonates receiving vancomycin or aminoglycoside therapies. For neonates with invasive fungal infections, the development of new antifungal agents has significantly improved therapeutic outcomes in recent years. Liposomal amphotericin B has been found to be safe and efficacious in patients with renal impairment or toxicity caused by conventional amphotericin B. Antifungal prophylaxis with fluconazole has also been reported to dramatically reduce rates of neonatal invasive fungal infections and to improve long-term neurodevelopmental outcomes among treated children. Additionally, several large multicenter studies are currently investigating the safety and efficacy of oral lactoferrin as an immunoprophylactic agent for the prevention of neonatal sepsis.

Background: Rotavirus is the most common cause of infectious diarrhea in children worldwide. Recent studies have described changes in the burden of all-cause gastroenteritis; however, there are limited data on the clinical and economic impact of rotavirus vaccine on cases of laboratory-confirmed rotavirus disease., Methods: We performed a retrospective study of laboratory-confirmed rotavirus disease from July 2003 through June 2010 at a children's hospital and a community hospital in Utah. Demographics and hospital costs for children <5 years with rotavirus symptoms and a positive rotavirus enzyme immunoassay test on a stool specimen were abstracted from electronic medical records. We compared the prevaccine period (2003-2007) with the postvaccine period (2008-2010)., Results: The overall incidence of rotavirus gastroenteritis declined in the postvaccine period, from 26.6 to 5.2 cases per 10 000 person-years for Salt Lake County residents. The largest decrease in the incidence of rotavirus gastroenteritis was among children <12 months (-87%; 95% confidence interval [CI], 79-93). Older children (12-23 months) also experienced significant decreases (-81%; 95% CI, 72-88), as did those 24-59 months (-61%; 95% CI, 51-71). In 2009, 3 years after rotavirus vaccine introduction, there was a 79% decrease in emergency department visits and a 78% decrease in hospitalizations across both hospitals. The cost of emergency department visits and hospitalizations for rotavirus gastroenteritis decreased by 79% and 72%, respectively, resulting in annual savings of $790 000 at a children's hospital and $140 000 at a community hospital., Conclusion: Rotavirus vaccination in infants has dramatically decreased the clinical burden and direct medical costs of rotavirus gastroenteritis in both infants and young children., (© The Author 2012. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

We report the second human case of Bartonella vinsonii subsp. berkhoffii endocarditis in a 19-year-old male with congenital heart disease. Diagnosis was established by Bartonella antibodies detected by immunofluorescence, and polymerase chain reaction amplification and sequencing from blood.

Background: A small group of children have second and even more cerebrospinal fluid (CSF) shunt infections (SIs). We sought to describe the treatment approaches used for, and the microbiology of, repeated SIs., Methods: The study population included 31 children with second shunt infection (SI-2) among those undergoing initial CSF shunt placement and treatment for initial infection at Primary Children's Medical Center. CSF SI was defined as follows: (1) presence of bacteria in Gram stain and/or culture of CSF, wound, and/or pseudocyst; (2) visible hardware; (3) abdominal pseudocyst; or (4) presence of bacteria in a blood culture in children with a ventriculoatrial shunt. Infection rates were generated using per-patient denominators, and the concordance of organisms across infections was summarized., Results: Of the 31 children with SI-2, most were less than 6 months of age at initial shunt placement (81%), male (77%), and with ventriculoperitoneal shunts (71%). Of total, 18 developed SI-3 and 8 developed SI-4. Infection rates were 60% (95% confidence interval [CI]: 42%-75%, n = 18/30) for SI-3 and 47% (95% CI: 26%-69%, n = 8/17) for SI-4. The median time to SI-3 was 477 days (range, 5-828) and to SI-4 it was 2137 days (range, 9-2137). Gram-positive organisms predominated (93% of SI-2, 94% of SI-3). The majority of SI-2 demonstrated Gram-stain concordance with both the initial (first) SI (58%, 95% CI: 41%-74%) and with the following (third) SI (78%, 95% CI: 55%-91%)., Conclusions: Children with SI-2 experience high subsequent reinfection rates with a long time to reinfection.

Non-pharmaceutical interventions, including social distancing, quarantine, and isolation, are a potentially attractive means to limit the transmission of a pandemic virus. Many of these interventions are directed at children given children's disproportionate role in amplifying epidemics. The ethics of non-pharmaceutical interventions can be analyzed using Nancy Kass' ethics framework for public health. Such an analysis highlights the limited data supporting these interventions' effectiveness. It also suggests the framework itself needs to be expanded to consider harms other than constraints on liberty and to consider affirmative programs to mitigate these broader harms.

The authors report on a case of intracranial candidiasis in an immunocompetent neonate with a ventriculo-peritoneal shunt. The child was known to be colonized with yeast as she had been treated for oral thrush; however, she did not have systemic candidiasis. Despite initial treatment with antifungal medication, intraventricular fungus balls developed that were visible on imaging and confirmed with pathological analysis. Multiple endoscopic intraventricular operations were required for excision of the initial and recurrent fungus balls, multiple fenestrations of loculations and cysts were performed, and ultimately 3 ventriculoperitoneal shunts were placed. The finding of an intraventricular fungus ball is a unique manifestation of intracranial candidiasis, and to the authors' knowledge has not been previously reported in the English literature.

Nontuberculous mycobacteria (NTM) are ubiquitous in nature and have been implicated in skin/soft-tissue, pulmonary, middle ear, bone, and surgical/traumatic wound infections. Disseminated disease occurs infrequently and almost exclusively in the immunocompromised. We describe the first 2 reported cases of disseminated Mycobacterium fortuitum infection in teenagers with sickle hemoglobinopathy. Both had central venous catheters (CVCs), frequent admissions for vaso-occlusive painful episode and received hydroxyurea. Diagnosis was confirmed by multiple positive blood cultures and pulmonary dissemination occurred in both. Both had successful treatment after CVC removal and combination drug therapy. Positive cultures persisted in 1 patient due to drug resistance emphasizing the need for accurate susceptibility data. NTM infection should be added to the list of pathogens in sickle cell patients with CVCs and fever. Investigation for disseminated disease should be undertaken based on clinical signs and symptoms. Although some routine blood culture systems can identify NTM, specific mycobacterial blood culture is optimal. Removal of involved CVCs is essential and treatment of NTM must be guided by susceptibilities. As dissemination almost always occurs in those with impaired cellular immunity, human immunodeficiency virus testing should be performed. Hydroxyurea may be a risk factor for dissemination and needs further evaluation.