First name
Rachel
Middle name
L
Last name
Wattier

Title

Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents.

Year of Publication

2022

Date Published

2022 Jan 20

ISSN Number

1537-6591

Abstract

<p><strong>BACKGROUND: </strong>Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear.</p>

<p><strong>METHODS: </strong>This multinational observational cohort study enrolled patients aged &gt;120 days and &lt;18 years with concern for IC from 1 January 2015 to 26 September 2019 at 25 centers. Blood collected at onset of symptoms was tested using T2Candida, Fungitell (1→3)-β-D-glucan, Platelia Candida Antigen (Ag) Plus, and Platelia Candida Antibody (Ab) Plus assays. Operating characteristics were determined for each biomarker, and assays meeting a defined threshold considered in combination. Sterile site cultures were the reference standard.</p>

<p><strong>RESULTS: </strong>Five hundred participants were enrolled at 22 centers in 3 countries, and IC was diagnosed in 13 (2.6%). Thirteen additional blood specimens were collected and successfully spiked with Candida species, to achieve a 5.0% event rate. Valid T2Candida, Fungitell, Platelia Candida Ag Plus, and Platelia Candida Ab Plus assay results were available for 438, 467, 473, and 473 specimens, respectively. Operating characteristics for T2Candida were most optimal for detecting IC due to any Candida species, with results as follows: sensitivity, 80.0% (95% confidence interval, 59.3%-93.2%), specificity 97.1% (95.0%-98.5%), positive predictive value, 62.5% (43.7%-78.9%), and negative predictive value, 98.8% (97.2%-99.6%). Only T2Candida and Platelia Candida Ag Plus assays met the threshold for combination testing. Positive result for either yielded the following results: sensitivity, 86.4% (95% confidence interval, 65.1%- 97.1%); specificity, 94.7% (92.0%-96.7%); positive predictive value, 47.5% (31.5%-63.9%); and negative predictive value, 99.2% (97.7%-99.8%).</p>

<p><strong>CONCLUSIONS: </strong>T2Candida alone or in combination with Platelia Candida Ag Plus may be beneficial for rapid detection of Candida species in children with concern for IC.</p>

<p><strong>CLINICAL TRIALS REGISTRATION: </strong>NCT02220790.</p>

DOI

10.1093/cid/ciab928

Alternate Title

Clin Infect Dis

PMID

35134165

Title

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

Year of Publication

2022

Date Published

2022 Feb 02

ISSN Number

2048-7207

Abstract

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

DOI

10.1093/jpids/piab124

Alternate Title

J Pediatric Infect Dis Soc

PMID

35107571

Title

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

Year of Publication

2021

Date Published

2021 Aug 10

ISSN Number

2048-7207

Abstract

<p><strong>BACKGROUND: </strong>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.</p>

<p><strong>METHODS: </strong>This multinational observational cohort study enrolled patients aged &gt;120 days and &lt;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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

<p><strong>CLINICAL TRIALS REGISTRATION: </strong>NCT01869829.</p>

DOI

10.1093/jpids/piab024

Alternate Title

J Pediatric Infect Dis Soc

PMID

34374424

Title

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

Year of Publication

2021

Date Published

2021 Jan 03

ISSN Number

2048-7207

Abstract

<p><strong>BACKGROUND: </strong>In November 2020, the US Food and Drug Administration (FDA) provided Emergency Use Authorizations (EUA) for two novel virus-neutralizing monoclonal antibody therapies, bamlanivimab, and REGN-COV2 (casirivimab plus imdevimab), for the treatment of mild to moderate 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.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>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 implementation of a system for safe and timely administration that does not exacerbate existing healthcare disparities.</p>

DOI

10.1093/jpids/piaa175

Alternate Title

J Pediatric Infect Dis Soc

PMID

33388760

Title

Multicenter interim guidance on use of antivirals for children with COVID-19/SARS-CoV-2.

Year of Publication

2020

Date Published

2020 Sep 12

ISSN Number

2048-7207

Abstract

<p><strong>BACKGROUND: </strong>Although Coronavirus Disease 2019 (COVID-19) is a mild infection in most children, a small proportion develop severe or critical illness. Data evaluating agents with potential antiviral activity continue to expand, such that updated guidance is needed regarding use of these agents in children.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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 non-invasive or invasive mechanical ventilation or extra-corporeal 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 non-invasive 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.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

DOI

10.1093/jpids/piaa115

Alternate Title

J Pediatric Infect Dis Soc

PMID

32918548

Title

Return to School for Pediatric Solid Organ Transplant Recipients in the United States During the COVID-19 Pandemic: Expert Opinion on Key Considerations and Best Practices.

Year of Publication

2020

Date Published

2020 Aug 04

ISSN Number

2048-7207

Abstract

<p>The COVID-19 pandemic has created many challenges for pediatric solid organ transplant (SOT) recipients and their families. As the pandemic persists, patients and their families struggle to identify the best and safest practices for resuming activities as areas re-open. In particular, decisions about returning to school remain difficult. We assembled a team of pediatric infectious diseases, transplant infectious diseases, public health, transplant psychology, and infection prevention and control specialists to address the primary concerns about school re-entry for pediatric SOT recipients in the United States. Based on available literature and guidance from national organizations, we generated consensus statements pertaining to school re-entry specific to pediatric SOT recipients. Although data are limited, and the COVID-19 pandemic highly dynamic, our goal was to create a framework from which providers and caregivers can identify the most important considerations for each pediatric SOT recipient to promote a safe return to school this fall.</p>

DOI

10.1093/jpids/piaa095

Alternate Title

J Pediatric Infect Dis Soc

PMID

32750142

Title

Multicenter initial guidance on use of antivirals for children with COVID-19/SARS-CoV-2.

Year of Publication

2020

Date Published

2020 Apr 22

ISSN Number

2048-7207

Abstract

<p><strong>BACKGROUND: </strong>Although Coronavirus Disease 2019 (COVID-19) is mild in nearly all children, a small proportion of pediatric patients develops severe or critical illness. Guidance is therefore needed regarding use of agents with potential activity against severe acute respiratory syndrome coronavirus 2 in pediatrics.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>Antiviral therapy for COVID-19 is not necessary for the great majority of pediatric patients. For those rare children who develop severe or critical disease, this guidance offer 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.</p>

DOI

10.1093/jpids/piaa045

Alternate Title

J Pediatric Infect Dis Soc

PMID

32318706

Title

Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia.

Year of Publication

2017

Date Published

2017 May 23

ISSN Number

1097-0142

Abstract

<p><strong>BACKGROUND: </strong>Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness.</p>

<p><strong>METHODS: </strong>A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables.</p>

<p><strong>RESULTS: </strong>From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI.</p>

<p><strong>CONCLUSIONS: </strong>The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017. © 2017 American Cancer Society.</p>

DOI

10.1002/cncr.30792

Alternate Title

Cancer

PMID

28542918

Title

A Prospective, International Cohort Study of Invasive Mold Infections in Children.

Year of Publication

2015

Number of Pages

313-22

Date Published

2015 Dec

ISSN Number

2048-7207

Abstract

<p><strong>BACKGROUND: </strong>Invasive mold infections (IMIs) are a leading cause of mortality in immunocompromised children, yet there has never been an international epidemiologic investigation of pediatric IMIs.</p>

<p><strong>METHODS: </strong>This international, prospective cohort study was performed to characterize the epidemiology, antifungal therapy, and outcomes of pediatric IMIs. Children (≤18 years) with proven or probable IMIs were enrolled between August 2007 and May 2011 at 22 sites. Risk factors, underlying diagnoses, and treatments were recorded. Outcomes were assessed at 12 weeks after diagnosis using European Organization for Research and Treatment of Cancer/Mycoses Study Group response criteria.</p>

<p><strong>RESULTS: </strong>One hundred thirty-one pediatric patients with IMIs were enrolled; the most common IMI was invasive aspergillosis ([IA] 75%). Children with IA and those with other types of IMIs had similar underlying risk factors, except that children with IMIs caused by non-Aspergillus species were more likely to have received mold-active antifungal agents preceding diagnosis. The most commonly used antifungal classes after diagnosis were triazoles (82%) and polyenes (63%). Combination therapy was used in 53% of patients. Use of combination therapy was associated with an increased risk of adverse events (risk ratio, 1.98; 95% confidence interval, 1.06-3.68; P = .031), although there was no detectable difference in outcome.</p>

<p><strong>CONCLUSIONS: </strong>Although risk factors for IMIs are similar across specific subtypes, preceding antifungal therapy may be an important modifier. Combination antifungal therapy requires further study to determine its true risks and benefits.</p>

DOI

10.1093/jpids/piu074

Alternate Title

J Pediatric Infect Dis Soc

PMID

26582870

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