Long COVID and recovery from Long COVID: quality of life impairments and subjective cognitive decline at a median of 2 years after initial infection.

BACKGROUND: Recovery from SARS CoV-2 infection is expected within 3 months. Long COVID occurs after SARS-CoV-2 when symptoms are present for more than 3 months that are continuous, relapsing and remitting, or progressive. Better understanding of Long COVID illness trajectories could strengthen patient care and support. METHODS: We characterized functional impairments, quality of life (QoL), and cognition among patients who recovered from SARS-CoV-2 infection within 3 months (without Long COVID), after 3 months (Recovered Long COVID), or remained symptomatic (Long COVID). Among 7305 patients identified with previous SARS-CoV-2 infection between March 2020 and December 2021, confirmed in the medical record with laboratory test or physician diagnosis, 435 (6%) completed a single self-administered survey between March 2022 and September 2022. Multi-domain QoL and cognitive concerns were evaluated using PROMIS-29 and the Cognitive Change Index-12. RESULTS: Nearly half the participants (47.7%) were surveyed more than 2 years from initial infection (median = 23.3 months; IQR = 18.6, 26.7) and 86.7% were surveyed more than 1 year from infection. A significantly greater proportion of the Long COVID (n = 215) group, (Current and Recovered combined), had moderate-to-severe impairment in all health domains assessed compared to those Without Long COVID (n = 220; all p < 0.05). The Recovered Long COVID group (n = 34) had significantly lower prevalence of fatigue, pain, depression, and physical and social function impairment compared to those with Current Long COVID (n = 181; all p < 0.05). However, compared to patients Without Long COVID, the Recovered Long COVID group had greater prevalences of fatigue, pain (p ≤ 0.06) and subjective cognitive decline (61.8% vs 29.1%; p < 0.01). Multivariate relative risk (RR) regression indicated Long COVID risk was greater for older age groups (RR range 1.46-1.52; all p ≤ 0.05), those without a bachelor's degree (RR = 1.33; 95% CI = 1.03-1.71; p = 0.03), and those with 3 or more comorbidities prior to SARS-CoV-2 infection (RR = 1.45; 95% CI = 1.11-1.90; p < 0.01). CONCLUSIONS: Long COVID is associated with long-term subjective cognitive decline and diminished quality of life. Clinically significant cognitive complaints, fatigue, and pain were present even in those who reported they had recovered from Long COVID. These findings have implications for the sustainability of participation in work, education, and social activities.

Changes in Inhaled Nitric Oxide Use Across ICUs After Implementation of a Standard Pathway.

OBJECTIVES: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator. It is expensive, frequently used, and not without risk. There is limited evidence supporting a standard approach to initiation and weaning. Our objective was to optimize the use of iNO in the cardiac ICU (CICU), PICU, and neonatal ICU (NICU) by establishing a standard approach to iNO utilization. DESIGN: A quality improvement study using a prospective cohort design with historical controls. SETTING: Four hundred seven-bed free standing quaternary care academic children's hospital. PATIENTS: All patients on iNO in the CICU, PICU, and NICU from January 1, 2017 to December 31, 2022. INTERVENTIONS: Unit-specific standard approaches to iNO initiation and weaning. MEASUREMENTS AND MAIN RESULTS: Sixteen thousand eighty-seven patients were admitted to the CICU, PICU, and NICU with 9343 in the pre-iNO pathway era (January 1, 2017 to June 30, 2020) and 6744 in the postpathway era (July 1, 2020 to December 31, 2022). We found a decrease in the percentage of CICU patients initiated on iNO from 17.8% to 11.8% after implementation of the iNO utilization pathway. We did not observe a change in iNO utilization between the pre- and post-iNO pathway eras in either the PICU or NICU. Based on these data, we estimate 564 total days of iNO (-24%) were saved over 24 months in association with the standard pathway in the CICU, with associated cost savings. CONCLUSIONS: Implementation of a standard pathway for iNO use was associated with a statistically discernible reduction in total iNO usage in the CICU, but no change in iNO use in the NICU and PICU. These differential results likely occurred because of multiple contextual factors in each care setting.

The Impact of an Emergency Department Bruising Pathway on Disparities in Child Abuse Evaluation.

OBJECTIVES: Previous research has shown racial, ethnic, and socioeconomic disparities in provider medical evaluations and reporting to child protective services (CPS) and law enforcement (LE) for cases of suspected child physical abuse. Our hospital standardized evaluation and reporting of high-risk bruising using a clinical pathway. We aimed to assess whether standardization impacted disparity. METHODS: We performed a retrospective observational study including children evaluated in the emergency department who had a social work consult for concern for child abuse or neglect between June 2012 and December 2019. From this group, we identified children with high-risk bruising. We compared outcomes (receipt of skeletal survey, CPS report, or LE report) before and after implementation of a standard bruising evaluation pathway to determine how the intervention changed practice among various racial, ethnic, and socioeconomic groups. RESULTS: During the study period, 2129 children presented to the ED and received a social work consult for child abuse or neglect. Of these, 333 had high-risk bruising. Children without private insurance had a higher risk of having a CPS (adjusted relative risk, 1.32; 95% confidence interval, 1.09-1.60) or LE (adjusted relative risk, 1.48; 95% confidence interval, 1.11-1.97) report prepathway, but not after pathway implementation. No significant associations were seen for race or ethnicity. CONCLUSIONS: A standardized clinical pathway for identification and evaluation of high-risk bruising may help to decrease socioeconomic disparities in reporting high-risk bruising. Larger studies are needed to fully evaluate disparities in assessment and reporting of child abuse.

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case-control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case-control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3-3.4), and exposure to third- (OR 2.4, 95% CI 1.4-4.2) or fourth-generation (OR 2.1, 95% CI 1.2-3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3-0.9). Ninety-two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1-5.4) and third-generation cephalosporin therapy (OR 3.9, 95% CI 1.4-10.5) were identified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.

Mycobacterium grossiae sp. nov., a rapidly growing, scotochromogenic species isolated from human clinical respiratory and blood culture specimens.

A previously undescribed, rapidly growing, scotochromogenic species of the genus Mycobacterium (represented by strains PB739T and GK) was isolated from two clinical sources - the sputum of a 76-year-old patient with severe chronic obstructive pulmonary disease, history of tuberculosis exposure and Mycobacterium avium complex isolated years prior; and the blood of a 15-year-old male with B-cell acute lymphoblastic leukaemia status post bone marrow transplant. The isolates grew as dark orange colonies at 25-37 °C after 5 days, sharing features in common with other closely related species. Analysis of the complete 16S rRNA gene sequence (1492 bp) of strain PB739T demonstrated that the isolate shared 98.8 % relatedness with Mycobacterium wolinskyi. Partial 429 bp hsp65 and 744 bp rpoB region V sequence analyses revealed that the sequences of the novel isolate shared 94.8 and 92.1 % similarity with those of Mycobacterium neoaurum and Mycobacterium aurum, respectively. Biochemical profiling, antimicrobial susceptibility testing, HPLC/gas-liquid chromatography analyses and multilocus sequence typing support the taxonomic status of these isolates (PB739T and GK) as representatives of a novel species. Both isolates were susceptible to the Clinical and Laboratory Standards Institute recommended antimicrobials for susceptibility testing of rapidly growing mycobacteria including amikacin, ciprofloxacin, moxifloxacin, doxycycline/minocycline, imipenem, linezolid, clarithromycin and trimethropin/sulfamethoxazole. Both isolates PB739T and GK showed intermediate susceptibility to cefoxitin. We propose the name Mycobacterium grossiae sp. nov. for this novel species and have deposited the type strain in the DSMZ and CIP culture collections. The type strain is PB739T (=DSM 104744T=CIP 111318T).

Cytomegalovirus in immunocompromised children.

PURPOSE OF REVIEW: The purpose of this study is to explore the latest developments in the risk factors, prevention and treatment of cytomegalovirus (CMV) infection in immunocompromised children, including those with congenital immunodeficiency or iatrogenic immune suppression related to solid organ transplantation (SOT) or haematopoietic cell transplantation (HCT). RECENT FINDINGS: CMV viral load measurements now have international standards, allowing for more reliable comparison across sites and within individuals. Preemptive and prophylactic therapy with routine CMV monitoring in transplant patients has yielded significant reduction in CMV morbidity and mortality in these patients. The majority of U.S. states have adopted routine newborn screening for severe combined immunodeficiency (SCID). Viral infections, including CMV, are a major obstacle preventing optimal curative transplantation in these patients. Several new antiviral agents are currently being investigated for CMV infection in immunocompromised patients. Knowledge on CMV drug resistance in children is emerging and requires further study. SUMMARY: Conditions that diminish cell-mediated immunity impact the development of CMV infection and disease. These conditions include certain congenital immunodeficiencies and SOT and HCT. Infants identified as having SCID should be screened for CMV risk factors. A preemptive or prophylactic strategy should be chosen for CMV management in children who are high risk posttransplantation. In those who develop disease, viral loads should be monitored and resistance testing considered if response is not deemed adequate. Oral valganciclovir is being used as an alternative to ganciclovir in children, although pharmacokinetic data are limited. Other oral antiviral agents under development are promising future options for paediatric CMV therapy.

Cytomegalovirus Cell-mediated Immunity Assays in Pediatric Transplantation.

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in pediatric transplantation. However, currently utilized CMV prevention paradigms have limitations, leading to research aimed at novel strategies for mitigation of CMV infection. Cell-mediated immunity (CMI) is crucial in controlling CMV infection and the use of CMV-specific CMI assays to guide prevention and treatment of CMV infection in both solid organ transplant and hematopoietic cell transplant recipients shows great promise. In this article, we review the immune response to CMV infection to highlight the rationale for CMI assays, describe available commercial assays and strategies for their use, and summarize relevant literature regarding the use of CMI assays in transplant recipients.

Guidance for prevention and management of COVID-19 in children and adolescents: A consensus statement from the Pediatric Infectious Diseases Society Pediatric COVID-19 Therapies Taskforce.

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.

How we treat diarrhea in pediatric transplant patients: a brief review.

Diarrhea is a common problem faced by both hematopoietic and solid organ transplant recipients. The differential diagnosis is wide, ranging from infectious to non-infectious causes and from benign to emergent illness. Here we present two patients with diarrhea and discuss our approaches to the diagnostic evaluation and management of transplant recipients with diarrhea. We also include a review of the literature and discuss areas in need of further study.

Monoclonal Antibody and Antiviral Therapy for Mild-to-Moderate COVID-19 in Pediatric Patients.

Multiple antiviral and monoclonal antibody therapies are now available for mild-moderate COVID-19 in high-risk patients ≥12 years of age. However, data for the use of these agents in children is limited. We reviewed 94 pediatric patients for whom early therapy was requested since the emergence of the Omicron variant and describe patient characteristics, treatment logistics and associated short-term events.

Monoclonal Antibody Use for Coronavirus Disease 2019 in Pediatric Patients: A Multicenter Retrospective Study.

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.

Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network.

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.

An unusual case of incomplete Kawasaki disease in an adolescent returning from holiday in Montana.

Here we present an unusual case of incomplete Kawasaki disease in a 15-year-old boy returning from a holiday with his family in Montana. His symptoms were initial diarrhoea and lethargy, with fever, rash, conjunctivitis, and arthralgia developing during the course of his illness. His condition worsened while he was at his local hospital, and he was transferred to the regional tertiary paediatric hospital. An initial echocardiogram was normal; however, repeat echocardiogram showed dilated coronary arteries with subsequent development of peeling of the skin on the hands and feet. The patient was started on intravenous immunoglobulin and high-dose aspirin and improved clinically. He was discharged home and remains under follow-up by the infectious diseases and cardiology teams.

Neonatal Herpes Simplex Virus Infection: Epidemiology and Outcomes in the Modern Era.

BACKGROUND: Over the past several decades, there have been advances in diagnosis and treatment of neonatal herpes simplex virus (HSV) disease. There has been no recent comprehensive evaluation of the impact of these advances on the management and outcomes for neonates with HSV. METHODS: Clinical data for initial presentation, treatment, and outcomes were abstracted from medical records of neonates with HSV treated at Seattle Children's Hospital between 1980 and 2016. RESULTS: One hundred thirty infants with a diagnosis of neonatal HSV were identified. Between 1980 and 2016, high-dose acyclovir treatment for neonatal HSV infection increased from 0% to close to 95%, with subsequent decrease in overall HSV-related mortality from 20.9% to 5.6%. However, even among infants treated with high-dose acyclovir, mortality was 40.9% for infants with disseminated (DIS) disease, and only 55% of infants with central nervous system (CNS) disease were without obvious neurologic abnormalities at 24 months. Over the study period, the time between initial symptoms and diagnosis decreased. Skin recurrences were more common with HSV-2 than HSV-1 (80% vs 55%; P = .02) and in infants with lesions at initial diagnosis (76% vs 47%; P = .02). CONCLUSION: Changes in the standard of care for management of neonatal HSV disease have led to improvements in timeliness of diagnosis and outcome but mortality in infants with DIS disease and neurologic morbidity in infants with CNS disease remain high. Future research should focus on prevention of perinatal infection and subsequent recurrences.

Improving Care for Children with Bloody Diarrhea at Risk for Hemolytic Uremic Syndrome.

INTRODUCTION: Children with infectious bloody diarrhea are at an increased risk for developing hemolytic uremic syndrome (HUS). Early intervention may improve outcomes. This study evaluated the impact of a clinical pathway designed to identify those at risk for HUS, guide initial management, and provide decision support regarding patient disposition. METHODS: We performed a retrospective cohort study of children 4 months to 19 years of age who presented with the acute onset of bloody diarrhea or other HUS risk factors to the pediatric emergency department (ED) from September 2015 through July 2020. A rapid stool polymerase chain reaction (PCR) test became available in May 2017. The clinical pathway was implemented in January 2018. We used Fisher's exact tests and statistical process control charts to analyze patient- and system-level changes following pathway implementation. RESULTS: Three hundred five patients were included. Postimplementation, stool PCR use increased (78%-91%), hospitalization decreased (49%-30%), and mean total charges decreased ($7715-$6797). There were increases in length of stay (226-288 minutes) and charges ($2651-$3524) for patients discharged from the ED. All changes met rules for special cause variation. There was no change in early IV fluid administration, inpatient length of stay, ED return visits, hospital readmissions, or patients with Shiga toxin-producing Escherichia coli (STEC), acute kidney injury (AKI) or HUS. CONCLUSIONS: For children presenting to the ED with bloody diarrhea, introduction of a rapid stool PCR test and clinical pathway correlated with decreased hospitalizations and overall costs without adverse clinical outcomes.

Adverse pregnancy outcomes after in vitro fertilization due to undiagnosed urogenital tuberculosis and proposed screening algorithm for patients from tuberculosis-endemic countries.

Objective: To report 2 cases of adverse pregnancy outcomes due to delayed diagnosis of urogenital tuberculosis and propose a screening algorithm for patients from tuberculosis-endemic countries. Design: Case report. Setting: Academic medical center. Patients: Two patients with delayed diagnosis of urogenital tuberculosis leading to a fetal loss and a preterm delivery of an infant with congenital tuberculosis. Interventions: Endometrial biopsy, acid-fast bacilli culture of urine, and endometrium. Main outcome measures: Pregnancy outcomes. Results: Fetal loss at 19 weeks and preterm delivery of an infant with congenital tuberculosis before urogenital tuberculosis treatment. Conclusions: Patients who are at risk of urogenital tuberculosis should be screened in advance of infertility treatment to potentially prevent adverse pregnancy outcomes.

Updated Guidance on Use and Prioritization of Monoclonal Antibody Therapy for Treatment of COVID-19 in Adolescents.

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.

Initial Guidance on Use of Monoclonal Antibody Therapy for Treatment of Coronavirus Disease 2019 in Children and Adolescents.

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.

Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.

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.