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

comparative effectiveness invasive candidiasis pediatrics

Journal

Journal of the Pediatric Infectious Diseases Society
ISSN: 2048-7207
Titre abrégé: J Pediatric Infect Dis Soc
Pays: England
ID NLM: 101586049

Informations de publication

Date de publication:
10 Aug 2021
Historique:
received: 25 11 2020
accepted: 09 08 2021
entrez: 10 8 2021
pubmed: 11 8 2021
medline: 11 8 2021
Statut: aheadofprint

Résumé

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. 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. 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. 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. NCT01869829.

Sections du résumé

BACKGROUND 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 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 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 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 BACKGROUND
NCT01869829.

Identifiants

pubmed: 34374424
pii: 6347272
doi: 10.1093/jpids/piab024
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT01869829']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : National Institute of Allergy and Infectious Diseases
Organisme : NIH HHS
ID : 5R01AI103315
Pays : United States

Informations de copyright

© 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.

Auteurs

Brian T Fisher (BT)

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia Pennsylvania, USA.

Theoklis E Zaoutis (TE)

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia Pennsylvania, USA.

Rui Xiao (R)

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia Pennsylvania, USA.

Rachel L Wattier (RL)

Department of Pediatrics, Division of Infectious Diseases and Global Health, University of California-San Francisco, San Francisco, California, USA.

Elio Castagnola (E)

Infectious Diseases Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Zoi Dorothea Pana (ZD)

Infectious Disease Unit, 3rd Department of Pediatrics, Aristotle University and Hippokration Hospital, Thessaloniki, Greece.

Allison Fullenkamp (A)

Division of Pediatric Infectious Diseases, Duke University, Durham, North Carolina, USA.

Craig L K Boge (CLK)

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Rachael K Ross (RK)

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Inci Yildirim (I)

Division of Infectious Diseases, Department of Pediatrics Emory University, Atlanta, Georgia, USA.

Debra L Palazzi (DL)

Section of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.

Lara Danziger-Isakov (L)

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Surabhi B Vora (SB)

Department of Pediatrics, University of Washington and Seattle Children's Hospital, Seattle, Washington, USA.

Antonio Arrieta (A)

Division of Pediatric Infectious Diseases, Children's Hospital - Orange County, Orange, California, US.

Dwight E Yin (DE)

Division of Infectious Diseases, Department of Pediatrics, Children's Mercy and University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.

Martha Avilés-Robles (M)

Infectious Diseases Department, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.

Tanvi Sharma (T)

Division of Infectious Diseases Children's Hospital Boston, Boston, Massachusetts, USA.

Alison C Tribble (AC)

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Division of Infectious Diseases, Department of Pediatrics, University of Michigan and CS Mott Children's Hospital, Ann Arbor, Michigan, USA.

Gabriela Maron (G)

Department of Infectious Diseases St. Jude Children's Hospital, Memphis, Tennessee, USA.

David Berman (D)

Division of Pediatric Infectious Diseases, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.

Michael Green (M)

Division of Infectious Diseases, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.

Lillian Sung (L)

Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.

José Romero (J)

Division of Pediatric Infectious Diseases, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas, USA.

Sarmistha B Hauger (SB)

Pediatric Infectious Diseases, Dell Children's Medical Center, Austin, Texas, USA.

Emmanuel Roilides (E)

Infectious Disease Unit, 3rd Department of Pediatrics, Aristotle University and Hippokration Hospital, Thessaloniki, Greece.

Kiran Belani (K)

Pediatric Infectious Diseases, Children's Minnesota, Minneapolis, Minnesota, USA.

Dawn Nolt (D)

Division of Pediatric Infectious Diseases, Doernbecher Children's Hospital, Oregon Health & Science University, Portland, Oregon, USA.

Pere Soler-Palacin (P)

Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Barcelona, Spain.

Eduardo López-Medina (E)

Centro de Estudios en Infectología Pediátrica and Universidad del Valle, Cali Colombia.

William J Muller (WJ)

Division of Infectious Diseases, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Natasha Halasa (N)

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, US.

Daniel Dulek (D)

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, US.

Ibrahim Zaid Bin Hussain (IZB)

Pediatric Infectious Diseases King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.

Alice Pong (A)

Department of Pediatrics, University of California San Diego, San Diego, California, USA.

Jill Hoffman (J)

Pediatric Infectious Diseases, University of California Los Angeles, Los Angeles, California, USA.

Sujatha Rajan (S)

Division of Pediatric Infectious Diseases, Cohen Children's Medical Center, New Hyde Park, New York, USA.

Blanca E Gonzalez (BE)

Center for Pediatric Infectious Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Benjamin Hanisch (B)

Pediatric Infectious Diseases, Children's National Health System, Washington, DC, USA.

Catherine Aftandilian (C)

Pediatric Hematology/Oncology, Stanford University School of Medicine, Palo Alto, California, USA.

Fabianne Carlesse (F)

Instituto de Oncologia Pediatrica-IOP/GRAACC-UNIFESP, Sao Paulo, Brazil.

Mark J Abzug (MJ)

Division of Pediatric Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.

Anna R Huppler (AR)

Department of Pediatrics, Division of Infectious Diseases, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.

Christine M Salvatore (CM)

Department of Pediatrics, Division of Pediatric Infectious Diseases Weill Cornell Medicine, New York, New York, USA.

Monica I Ardura (MI)

Pediatric Infectious Diseases and Host Defense, Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, USA.

Arunaloke Chakrabarti (A)

Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Maria E Santolaya (ME)

Hospital Dr. Luis Calvo Mackenna, Facultad de Medicina, Universidad de Chile, Santiago, Chile.

A Russell Localio (AR)

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia Pennsylvania, USA.

William J Steinbach (WJ)

Division of Pediatric Infectious Diseases, Duke University, Durham, North Carolina, USA.

Classifications MeSH