title: A Prospective, International Cohort Study of Invasive Mold Infections in Children.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, University of California-San Francisco.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Wattier
authors.affiliation: Department of Pediatrics, University of California-San Francisco.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dvorak
authors.affiliation: Department of Pediatrics, University of Southern California School of Medicine, Los Angeles.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Hoffman
authors.affiliation: Department of Pediatrics, Duke University, Durham, North Carolina.
authors.forename: Ava A
authors.initials: AA
authors.lastname: Brozovich
authors.affiliation: Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Bin-Hussain
authors.affiliation: Department of Pediatric Hematology/Oncology, University Children's Hospital, Muenster, Germany.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Groll
authors.affiliation: Infectious Diseases Unit, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Castagnola
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Knapp
authors.affiliation: Division of Infectious Diseases, Children's Hospital of Philadelphia, Pennsylvania.
authors.forename: Theoklis E
authors.initials: TE
authors.lastname: Zaoutis
authors.affiliation: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Britt
authors.initials: B
authors.lastname: Gustafsson
authors.affiliation: Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Lillian
authors.initials: L
authors.lastname: Sung
authors.affiliation: Department of Pediatrics, All Children's Hospital, St. Petersburg, Florida.
authors.forename: David
authors.initials: D
authors.lastname: Berman
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Natasha B
authors.initials: NB
authors.lastname: Halasa
authors.affiliation: Department of Pediatrics, Children's Hospital Colorado, Aurora.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Abzug
authors.affiliation: Department of Microbiology, University of Athens, Greece.
authors.forename: Aristea
authors.initials: A
authors.lastname: Velegraki
authors.affiliation: Division of Infectious Diseases, Boston Children's Hospital, Massachusetts.
authors.forename: Tanvi S
authors.initials: TS
authors.lastname: Sharma
authors.affiliation: Division of Infectious Diseases, Children's Hospital of Philadelphia, Pennsylvania.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Fisher
authors.affiliation: Department of Pediatrics, Duke University, Durham, North Carolina Department of Molecular Genetics & Microbiology, Duke University, Durham, North Carolina.
authors.forename: William J
authors.initials: WJ
authors.lastname: Steinbach
mesh_terms: D000293:Adolescent; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005658:Fungi; D006801:Humans; D008297:Male; D009181:Mycoses / Q000188:drug therapy* / Q000453:epidemiology*; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents
keywords: antifungal; aspergillosis; mucormycosis; outcome; treatment