Comparative Effectiveness of Echinocandins vs Triazoles or Amphotericin B Formulations as Initial Directed Therapy for Invasive Candidiasis in Children and Adolescents.
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Fisher Brian T, Zaoutis Theoklis E, Xiao Rui, Wattier Rachel L, Castagnola Elio, Pana Zoi Dorothea, Fullenkamp Allison, Boge Craig L K, Ross Rachael K, Yildirim Inci, Palazzi Debra L, Danziger-Isakov Lara, Vora Surabhi B, Arrieta Antonio, Yin Dwight E, Avilés-Robles Martha, Sharma Tanvi, Tribble Alison C, Maron Gabriela, Berman David, Green Michael, Sung Lillian, Romero José, Hauger Sarmistha B, Roilides Emmanuel, Belani Kiran, Nolt Dawn, Soler-Palacin Pere, López-Medina Eduardo, Muller William J, Halasa Natasha, Dulek Daniel, Hussain Ibrahim Zaid Bin, Pong Alice, Hoffman Jill, Rajan Sujatha, Gonzalez Blanca E, Hanisch Benjamin, Aftandilian Catherine, Carlesse Fabianne, Abzug Mark J, Huppler Anna R, Salvatore Christine M, Ardura Monica I, Chakrabarti Arunaloke, Santolaya Maria E, Localio A Russell, Steinbach William J
Аннотация
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: 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: 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: NCT01869829.