Rachel L Wattier1, Christopher C Dvorak1, Jill A Hoffman2, Ava A Brozovich3, Ibrahim Bin-Hussain4, Andreas H Groll5, Elio Castagnola6, Katherine M Knapp7, Theoklis E Zaoutis8, Britt Gustafsson9, Lillian Sung10, David Berman11, Natasha B Halasa12, Mark J Abzug13, Aristea Velegraki14, Tanvi S Sharma15, Brian T Fisher8, William J Steinbach16. 1. Department of Pediatrics, University of California-San Francisco. 2. Department of Pediatrics, University of Southern California School of Medicine, Los Angeles. 3. Department of Pediatrics, Duke University, Durham, North Carolina. 4. Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. 5. Department of Pediatric Hematology/Oncology, University Children's Hospital, Muenster, Germany. 6. Infectious Diseases Unit, Istituto Giannina Gaslini, Genoa, Italy. 7. Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee. 8. Division of Infectious Diseases, Children's Hospital of Philadelphia, Pennsylvania. 9. Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. 10. Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada. 11. Department of Pediatrics, All Children's Hospital, St. Petersburg, Florida. 12. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee. 13. Department of Pediatrics, Children's Hospital Colorado, Aurora. 14. Department of Microbiology, University of Athens, Greece. 15. Division of Infectious Diseases, Boston Children's Hospital, Massachusetts. 16. Department of Pediatrics, Duke University, Durham, North Carolina Department of Molecular Genetics & Microbiology, Duke University, Durham, North Carolina.
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.
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.
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