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Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was successful in 66 participants who transitioned to enteral therapy., (© 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.)

Objective: This manuscript calculates the estimated cost-savings associated with implementing criteria for multi-drug-resistant organisms (MDRO)., Design: The study evaluated extended-spectrum beta-lactamase (ESBL) producing Enterobacterales isolates utilizing the MDRO criteria established by Infection Prevention and Control. Isolates were categorized as either meeting or not meeting criteria. The number of inpatient days for patients with isolates not meeting criteria was calculated. The average daily cost of personal protective equipment (PPE) for patients in contact isolation was determined via literature review. Annual cost savings were determined by multiplying the total number of inpatient days by the average cost of PPE per day. Because our institution only isolates patients who meet the MDRO criteria, this approach was considered a cost-saving measure., Setting: 560 licensed bed, tertiary care facility in the United States., Patients: Adult inpatients between the years of 2019-2022 with an ESBL-producing Enterobacterales isolated from any specimen source., Results: 229 patients met inclusion criteria. 73% of isolates did not meet MDRO criteria. The patients with ESBL isolates not meeting criteria represented 2942 isolation days over four years. The average cost of PPE for contact isolation per day was $40.18. Cost-savings were estimated at $118,209 over four years., Conclusions: Our findings provide support for other healthcare systems to define organisms that warrant transmission-based contact precautions., Competing Interests: All authors report no conflicts of interest relevant to this article., (© The Author(s) 2024.)

Background: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown., Methods: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression., Results: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%)., Conclusions: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted., (© 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.)

Head lice infestation is associated with limited morbidity but causes a high level of anxiety among caregivers of school-aged children and adolescents. Since the 2015 clinical report on head lice was published by the American Academy of Pediatrics, new medications have been approved, and an algorithm for management of affected patients is included. This revised clinical report clarifies current diagnosis and treatment protocols., (Copyright © 2022 by the American Academy of Pediatrics.)

Importance: Blood culture overuse in the pediatric intensive care unit (PICU) can lead to unnecessary antibiotic use and contribute to antibiotic resistance. Optimizing blood culture practices through diagnostic stewardship may reduce unnecessary blood cultures and antibiotics., Objective: To evaluate the association of a 14-site multidisciplinary PICU blood culture collaborative with culture rates, antibiotic use, and patient outcomes., Design, Setting, and Participants: This prospective quality improvement (QI) collaborative involved 14 PICUs across the United States from 2017 to 2020 for the Bright STAR (Testing Stewardship for Antibiotic Reduction) collaborative. Data were collected from each participating PICU and from the Children's Hospital Association Pediatric Health Information System for prespecified primary and secondary outcomes., Exposures: A local QI program focusing on blood culture practices in the PICU (facilitated by a larger QI collaborative)., Main Outcomes and Measures: The primary outcome was blood culture rates (per 1000 patient-days/mo). Secondary outcomes included broad-spectrum antibiotic use (total days of therapy and new initiations of broad-spectrum antibiotics ≥3 days after PICU admission) and PICU rates of central line-associated bloodstream infection (CLABSI), Clostridioides difficile infection, mortality, readmission, length of stay, sepsis, and severe sepsis/septic shock., Results: Across the 14 PICUs, the blood culture rate was 149.4 per 1000 patient-days/mo preimplementation and 100.5 per 1000 patient-days/mo postimplementation, for a 33% relative reduction (95% CI, 26%-39%). Comparing the periods before and after implementation, the rate of broad-spectrum antibiotic use decreased from 506 days to 440 days per 1000 patient-days/mo, respectively, a 13% relative reduction (95% CI, 7%-19%). The broad-spectrum antibiotic initiation rate decreased from 58.1 to 53.6 initiations/1000 patient-days/mo, an 8% relative reduction (95% CI, 4%-11%). Rates of CLABSI decreased from 1.8 to 1.1 per 1000 central venous line days/mo, a 36% relative reduction (95% CI, 20%-49%). Mortality, length of stay, readmission, sepsis, and severe sepsis/septic shock were similar before and after implementation., Conclusions and Relevance: Multidisciplinary diagnostic stewardship interventions can reduce blood culture and antibiotic use in the PICU. Future work will determine optimal strategies for wider-scale dissemination of diagnostic stewardship in this setting while monitoring patient safety and balancing measures.

The purpose of this report is to educate providers about the risk of infectious diseases associated with emerging alternative peripartum and neonatal practices. This report will provide information pediatricians may use to counsel families before birth and to appropriately evaluate and treat neonates who have been exposed to these practices., Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they do not have a financial relationship relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Tuberculosis (TB) remains an important problem among children in the United States and throughout the world. There is no diagnostic reference standard for latent tuberculosis infection (also referred to as tuberculosis infection [TBI]). The tuberculin skin test (TST) has many limitations, including difficulty in administration and interpretation, the need for a return visit by the patient, and false-positive results caused by cross-reaction with Mycobacterium bovis-bacille Calmette-Guerin vaccines and many nontuberculous mycobacteria. Interferon-gamma release assays (IGRAs) are blood tests that use antigens specific for M tuberculosis; as a result, IGRAs yield fewer false-positive results than the TST. Both IGRAs and the TST have reduced sensitivity in immunocompromised children, including children with severe TB disease. Both methods have high positive predictive value when applied to children with risk factors for TBI, especially recent contact with a person who has TB disease. The advantages of using IGRAs and diminished experience with the placement and interpretation of the TST favor expanded use of IGRAs in children in the United States. There are now several effective and safe regimens for the treatment of TBI in children. For improved adherence to therapy, the 3 rifamycin-based regimens are preferred because of their short duration. Daily isoniazid can be used if there is intolerance or drug interactions with rifamycins. A TB specialist should be involved when there are questions regarding testing interpretation, selection of an appropriate treatment regimen, or management of adverse effects., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis., Methods: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups., Results: Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days., Conclusions: In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents., Clinical Trials Registration: NCT01869829., (© 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.)

Encephalitis is defined as altered mental status for more than 24 hours accompanied by 2 or more findings concerning for inflammation of the brain parenchyma: fever, seizures or other focal neurologic disorders, cerebrospinal fluid pleocytosis, and abnormal neuroimaging and electroencephalographic findings. Herpes simplex virus causes the most severe form of virus-induced encephalitis; the early administration of acyclovir can improve the prognosis of this disease. The rising interest in autoimmune causes of encephalitis, most notably anti- N -methyl-d-aspartate receptor, should prompt the clinician to consider immunomodulatory treatments, which may improve outcomes. A broad testing panel may be necessary to detect the etiologic agent; a few published pediatric cases suggest that infectious and autoimmune causes may occur concurrently in the same patient with encephalitis. More than 40% of children diagnosed as having encephalitis will not return to their previous level of neurologic function after resolution of their disease, although outcomes are highly variable depending on the etiologic agent., (© American Academy of Pediatrics, 2021. All rights reserved.)

Purpose of Review: The present coronavirus disease 2019 (COVID-19) pandemic has created additional challenges with an increased number of presumed healthy, full-term newborns being discharged at 24 h after delivery. Short lengths of stay raise the possibility of mother-infant dyads being less ready for discharge, defined as at least one of the three informants (i.e., mother, pediatrician, and obstetrician) believing that either the mother and/or infant should stay longer than the proposed time of discharge. This public health crisis has reduced the number of in-person well child visits, negatively impacting vaccine receipt, and anticipatory guidance., Recent Findings: Extra precautions should be taken during the transition period between postpartum discharge and follow-up in the ambulatory setting to ensure the safety of all patients and practice team members. This should include restructuring office flow by visit type and location, limiting in-person visits during well infant exams, instituting proper procedures for personal protective equipment and for cleaning of the office, expanding telehealth capabilities for care and education, and prioritizing universal vaccinations and routine well child screenings., Summary: Based on current limited evidence, this report provides guidance for the postdischarge management of newborns born to mothers with confirmed or suspected disease in the ambulatory setting as well as prioritizing universal immunizations and routine well child screenings during the COVID-19 pandemic.

Background: The infectious risk of central venous line (CVL) placement in children with neutropenia (absolute neutrophil count [ANC] <500/mm 3 ) is not well defined. This study aims to investigate the early (≤30 days) and late (>30 days) infectious complications of CVLs placed in pediatric patients with and without neutropenia., Methods: A retrospective review was conducted of all CVLs placed by pediatric surgeons at two institutions from 2010 to 2017. Multivariable logistic regression was performed to identify risk factors for line infection. Propensity score-matched cohorts of patients with and without neutropenia were compared in a 1:1 ratio. Wilcoxon rank-sum, Chi-square, Fisher's exact, and log-rank tests were also performed., Results: Review identified 1,102 CVLs placed in 937 patients. Fifty-four patients were neutropenic at the time of placement. Multivariable analysis demonstrated tunneled catheters and subclavian access as associated with line infection. The propensity score-matched cohort included 94 patients, 47 from each group. Demographic and preoperative data were similar between the groups (p > 0.05). Patients with neutropenia were no more likely to develop early (4.3% vs. 2.1%, p = 1.000) or late (19.1% vs. 17.0%, p = 1.000) infectious complications than patients without neutropenia, with similar median time to infection (141 vs. 222 days, p = 0.370)., Conclusion: A policy of selective CVL placement in neutropenic patients with standardized postoperative line maintenance is safe. Future directions include defining criteria by which neutropenic patients could be prospectively selected for safe CVL placement., Level of Evidence: II - Retrospective cohort study., Competing Interests: Conflict of interest The following authors have no financial disclosures: AJC, KVM, ED, SK, MWB, DN, MCH, NAH., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Staphylococcus aureus is a bacterium that can cause a variety of illnesses through suppurative or nonsuppurative (toxin-mediated) means. S aureus is a common cause of skin and skin structure infections as well as osteoarticular infections in the pediatric population. S aureus is also identified in cases of septicemia, infective endocarditis, pneumonia, ocular infections, and central nervous system infections. To design appropriate empirical therapy, pediatricians should be knowledgeable about the resistance patterns of S aureus in their communities, including methicillin and clindamycin resistance. This article reviews the microbiology, colonization and transmission, and antibiotic resistance of and clinical diseases caused by S aureus., (© American Academy of Pediatrics, 2018. All rights reserved.)

Cystic fibrosis (CF) is a chronic disorder characterized by acute pulmonary exacerbations that comprise increased cough, chest congestion, increased mucus production, shortness of breath, weight loss, and fatigue. Typically, severe episodes are treated in the inpatient setting and include intravenous antimicrobials, airway clearance therapy, and nutritional support. Children with less-severe findings can often be managed as outpatients with oral antimicrobials and increased airway clearance therapy at home without visiting the specialty CF center to begin treatment. Selection of specific antimicrobial agents is dependent on pathogens found in surveillance culture, activity of an agent in patients with CF, and the unique physiology of these patients. In this pediatric review, we present our practice for defining acute pulmonary exacerbation, deciding treatment location, initiating treatment either in-person or remotely, determining the frequency of airway clearance, selecting antimicrobial therapy, recommending timing for follow-up visit, and recognizing and managing treatment failures.

Background: Treatment of acute myeloid leukemia (AML) comes with a significant risk of life-threatening infection during periods of prolonged severe neutropenia. We studied the impact of preventive intravenous (IV) antibiotic administration at onset of absolute neutropenia on the incidence and outcome of life-threatening infections during treatment of childhood AML., Procedures: This is a retrospective study on pediatric patients (aged 0-18 years) consecutively diagnosed with de novo AML and treated at a single institution from April 2005 through February 2013. Patients were treated on the Children's Oncology Group (COG) AAML0531 protocol or with a modified United Kingdom Medical Research Council (UK MRC) AML 10 regimen. Pertinent data were extracted from hard copy or electronic chart review., Results: A total of 76 chemotherapy phases were analyzed from 29 patients. In each phase reported, preventive antibiotics were initiated when the daily absolute neutrophil count was <500 cells/mcl, before onset of fever. Seven episodes of bacteremia were documented with predominantly coagulase-negative staphylococci and viridans group streptococci. One infection-related death occurred, attributed to progressive respiratory failure occurring months after documented candidal pneumonia., Conclusions: Initiation of preventive antibiotics at the onset of absolute neutropenia was associated with no mortality from bacteremia. This preventive approach appears feasible and safe., (© 2015 Wiley Periodicals, Inc.)

Multicentric reticulohistiocytosis (MRH) is a rare systemic inflammatory granulomatous disease marked by severe and often rapidly progressive polyarticular arthritis and cutaneous papulonodules. Initial clinical diagnosis may be difficult. We describe a 2-year-old girl presenting with pink dermal papules on the forehead, thighs, elbows, knees, and palms of the hands. Based on clinical findings and skin biopsy results, she was initially diagnosed with granuloma annulare. At 5 years of age, she developed arthritis, fatigue, and more widespread skin papules leading to the diagnosis of MRH. To our knowledge, this is the youngest individual with MRH yet described. We outline the timeline and unique features of her case and review the literature pertaining to MRH in children. Although rare, MRH can be permanently debilitating, making prompt diagnosis critical. A standardized approach to investigation and management needs to be developed., (© 2015 Wiley Periodicals, Inc.)

Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three reported prior cases in the English-language literature. We describe a case of OL-HED-ID in a male infant who initially presented with congenital lymphedema, leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He subsequently developed gram-negative sepsis and multiple opportunistic infections including high-level cytomegalovirus viremia and Pneumocystis jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine sparse hair, and periorbital wrinkling, all features suggestive of ectodermal dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell dysfunction. Genetic testing revealed a novel mutation in the nuclear factor kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of OL-HED-ID. Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti. In this case, we report a novel mutation in the NEMO gene associated with OL-HED-ID. This article highlights the dermatologic manifestations of a rare disorder, OL-HED-ID, and underscores the importance of early recognition and prompt intervention to prevent life-threatening infections., (© 2013 Wiley Periodicals, Inc.)

Mycobacterium tuberculosis (Mtb) resides in a long-lived phagosomal compartment that resists maturation. The manner by which Mtb antigens are processed and presented on MHC Class I molecules is poorly understood. Using human dendritic cells and IFN-gamma release by CD8(+) T cell clones, we examined the processing and presentation pathway for two Mtb-derived antigens, each presented by a distinct HLA-I allele (HLA-Ia versus HLA-Ib). Presentation of both antigens is blocked by the retrotranslocation inhibitor exotoxin A. Inhibitor studies demonstrate that, after reaching the cytosol, both antigens require proteasomal degradation and TAP transport, but differ in the requirement for ER-golgi egress and new protein synthesis. Specifically, presentation by HLA-B8 but not HLA-E requires newly synthesized HLA-I and transport through the ER-golgi. Phenotypic analysis of the Mtb phagosome by flow organellometry revealed the presence of Class I and loading accessory molecules, including TAP and PDI. Furthermore, loaded HLA-I:peptide complexes are present within the Mtb phagosome, with a pronounced bias towards HLA-E:peptide complexes. In addition, protein analysis also reveals that HLA-E is enriched within the Mtb phagosome compared to HLA-A2. Together, these data suggest that the phagosome, through acquisition of ER-localized machinery and as a site of HLA-I loading, plays a vital role in the presentation of Mtb-derived antigens, similar to that described for presentation of latex bead-associated antigens. This is, to our knowledge, the first description of this presentation pathway for an intracellular pathogen. Moreover, these data suggest that HLA-E may play a unique role in the presentation of phagosomal antigens.

The primary goal of this study was to determine how chronic exposure to Ag influences the functionality of Mycobacterium tuberculosis-specific T cell responses. The frequency of IFN-gamma-producing effector CD4(+) and CD8(+) T cells dynamically changed during persistent M. tuberculosis infection. CD8(+) T cells used differential effector functions during acute and chronic phases of the immune response, where CD8(+) T cells produced negligible amounts of IFN-gamma early in infection, but switched to cytokine production during the chronic stage of infection. Using limiting dilution analysis, CD8(+) T cells isolated during the initial phase of infection demonstrated lytic potential, but this waned in the chronic stage. The apparent loss of cytotoxic activity was not associated with the lack of perforin. Ag dose could potentially govern the functional program of CD8(+) T cells. Collectively, these results depict a host immune response mounted against M. tuberculosis of a significantly more dynamic nature than previously recognized.

Reports of clinical manifestations of West Nile virus (WNV) infections in children have been relatively rare. Four cases of WNV infection in children are described: the first report of prolonged encephalitis and fulminant hepatitis caused by WNV, and 3 other presentations of WNV, including the first report of ocular involvement in a child.

Alternate modalities for the treatment of Mycobacterium tuberculosis are needed due to the rise in numbers of immunosuppressed individuals at risk for serious disease and the increasing prevalence of multidrug-resistant isolates. Interleukin-12 (IL-12) has been shown to improve immune responses against M. tuberculosis infection in both humans and mice. Previous studies using high-dose IL-12 in various disease models reported a paradoxical immunosuppression. We demonstrate here that exogenous administration of IL-12 for 8 weeks after an aerosolized low dose of M. tuberculosis results in increased survival and decreased pulmonary bacterial loads for CD4-T-cell-deficient mice, most likely due to an early increase in gamma interferon. IL-12 treatment did not impair or enhance the ability of the wild-type mice to control infection, as measured by bacterial numbers. Two novel findings are reported here regarding exogenous IL-12 therapy for M. tuberculosis infections: (i). IL-12 treatment resulted in decreased numbers of immune cells and reduced frequencies of lymphocytes (CD8(+), CD4(+), and NK cells) in the lungs of infected mice and (ii). IL-12 therapy reduced the pathology of M. tuberculosis-infected lungs, as granulomas were smaller and less numerous. These studies support an immunoregulatory role for IL-12 in tuberculosis.

Pulmonary disease caused by nontuberculous mycobacteria (NTM) is a relatively rare occurrence in immunocompetent children. Two cases of endobronchial NTM infection in immunocompetent children are described. In addition, 41 other children with NTM pulmonary disease reported in the English literature between 1930 and 2003 are reviewed. Clinical manifestations are either purely respiratory or respiratory with more widespread systemic symptoms. Compared with children with only respiratory complaints, children with constitutional symptoms from NTM pulmonary disease 1) had symptoms for a shorter period before presentation (10 vs 28 days), 2) had more radiographic evidence of pulmonary disease, and 3) were treated longer with antimycobacterial agents (11.5 months vs 6 months). The most common causative organism was Mycobacterium avium complex. Pediatricians should be increasingly aware of NTM in the differential diagnosis of persistent pulmonary disease in previously healthy children.

Congenital syphilis continues to occur despite the advances in testing of pregnant women in many countries and the availability of penicillin since 1943. This is a report of a child with multiple systemic manifestations of congenital syphilis. This is one of the few cases of survival with pituitary involvement from congenital syphilis and the first noted case in which diabetes insipidus developed. Institution of routine testing in all countries might have prevented the severe manifestations of syphilis seen in this child.