First name
Gabriela
Last name
Maron

Title

Influenza Vaccine in Pediatric Recipients of Hematopoietic-Cell Transplants.

Year of Publication

2023

Number of Pages

374-376

Date Published

01/2023

ISSN Number

1533-4406

DOI

10.1056/NEJMc2210825

Alternate Title

N Engl J Med

PMID

36630610

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

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

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

Year of Publication

2020

Date Published

2020 Feb 16

ISSN Number

1600-6143

Abstract

<p>Hematopoietic cell transplantation (HCT) and solid organ transplantation (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 (OR 2.6, 95% CI 1.5 - 4.7), proton-pump inhibitors (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.</p>

DOI

10.1111/ajt.15826

Alternate Title

Am. J. Transplant.

PMID

32064754

Title

A Multicenter Consortium to Define the Epidemiology and Outcomes of Inpatient Respiratory Viral Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients.

Year of Publication

2018

Number of Pages

275-282

Date Published

2018 Dec 3

ISSN Number

2048-7207

Abstract

<p><strong>Background: </strong>Respiratory virus infections (RVIs) pose a threat to children undergoing hematopoietic stem cell transplantation (HSCT). In this era of sensitive molecular diagnostics, the incidence and outcome of HSCT recipients who are hospitalized with RVI (H-RVI) are not well described.</p>

<p><strong>Methods: </strong>A retrospective observational cohort of pediatric HSCT recipients (between January 2010 and June 2013) was assembled from 9 US pediatric transplant centers. Their medical charts were reviewed for H-RVI events within 1 year after their transplant. An H-RVI diagnosis required respiratory signs or symptoms plus viral detection (human rhinovirus/enterovirus, human metapneumovirus, influenza, parainfluenza, coronaviruses, and/or respiratory syncytial virus). The incidence of H-RVI was calculated, and the association of baseline HSCT factors with subsequent pulmonary complications and death was assessed.</p>

<p><strong>Results: </strong>Among 1560 HSCT recipients, 259 (16.6%) acquired at least 1 H-RVI within 1 year after their transplant. The median age of the patients with an H-RVI was lower than that of patients without an H-RVI (4.8 vs 7.1 years; P &lt; .001). Among the patients with a first H-RVI, 48% required some respiratory support, and 14% suffered significant pulmonary sequelae. The all-cause and attributable case-fatality rates within 3 months of H-RVI onset were 11% and 5.4%, respectively. Multivariate logistic regression revealed that H-RVI onset within 60 days of HSCT, steroid use in the 7 days before H-RVI onset, and the need for respiratory support at H-RVI onset were associated with subsequent morbidity or death.</p>

<p><strong>Conclusion: </strong>Results of this multicenter cohort study suggest that H-RVIs are relatively common in pediatric HSCT recipients and contribute to significant morbidity and death. These data should help inform interventional studies specific to each viral pathogen.</p>

DOI

10.1093/jpids/pix051

Alternate Title

J Pediatric Infect Dis Soc

PMID

29106589

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