Multicenter Prospective Study of Biomarkers for Diagnosis of Invasive Candidiasis in Children and Adolescents

Author:

Fisher Brian T12,Boge Craig L K1,Xiao Rui2,Shuster Sydney1,Chin-Quee Dawn3,Allen John3,Shaheen Shareef3,Hayden Randall4,Suganda Sri4,Zaoutis Theoklis E12,Chang Yeh Chung3,Yin Dwight E5,Huppler Anna R6,Danziger-Isakov Lara7,Muller William J8,Roilides Emmanuel9,Romero José10,Sue Paul K11,Berman David12,Wattier Rachel L13,Halasa Natasha14,Dulek Daniel E14,Pong Alice15,Maron Gabriela16,Soler-Palacin Pere17,Hutto Susan C18,Gonzalez Blanca E19,Salvatore Christine M20,Rajan Sujatha21,Green Michael22,Doby Knackstedt Elizabeth23,Hauger Sarmistha B24,Steinbach William J3

Affiliation:

1. Children’s Hospital of Philadelphia , Philadelphia, Pennsylvania , USA

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

3. Duke University , Durham, North Carolina , USA

4. Department of Pathology, St Jude Children’s Research Hospital , Memphis, Tennessee , USA

5. Children’s Mercy and University of Missouri–Kansas City School of Medicine , Kansas City, Missouri , USA

6. Medical College of Wisconsin and Children’s Wisconsin , Milwaukee, Wisconsin , USA

7. Cincinnati Children’s Hospital Medical Center , Cincinnati, Ohio , USA

8. Northwestern University Feinberg School of Medicine , Chicago, Illinois , USA

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

10. Arkansas Children’s Hospital Research Institute , Little Rock, Arkansas , USA

11. University of Texas Southwestern Medical Center , Dallas, Texas , USA

12. John Hopkins All Children’s Hospital , St Petersburg, Florida , USA

13. University of California–San Francisco , San Francisco, California , USA

14. Vanderbilt University Medical Center , Nashville, Tennessee , USA

15. University of California San Diego , San Diego, California , USA

16. St Jude Children’s Research Hospital , Memphis, Tennessee , USA

17. Hospital Universitari Vall d’Hebron , Barcelona, Catalonia , Spain

18. University of Alabama , Birmingham, Birmingham, Alabama , USA

19. Cleveland Clinic Foundation , Cleveland, Ohio , USA

20. Weill Cornell Medicine , New York, New York , USA

21. Cohen Children’s Medical Center of New York , New Hyde Park, New York , USA

22. UPMC Children’s Hospital of Pittsburgh , Pittsburgh, Pennsylvania , USA

23. University of Utah , Salt Lake City, Utah , USA and

24. Dell Children’s Medical Center , Austin, Texas , USA

Abstract

Abstract Background Diagnosis of invasive candidiasis (IC) relies on insensitive cultures; the relative utility of fungal biomarkers in children is unclear. Methods This multinational observational cohort study enrolled patients aged >120 days and <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. Results 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%). Conclusions 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. Clinical Trials Registration NCT02220790.

Funder

National Institute of Allergy and Infectious Diseases, NIH

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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3. Comparative efficacy of echinocandins versus triazoles or amphotericin B formulations as initial directed therapy for invasive candidiasis in children and adolescents.;Fisher;J Pediatr Infect Dis Soc,2021

4. Early deaths and treatment-related mortality in children undergoing therapy for acute myeloid leukemia: analysis of the multicenter clinical trials AML-BFM 93 and AML-BFM 98.;Creutzig;J Clin Oncol,2004

5. The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study.;Pagano;Haematologica,2006

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