Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network

Rachel L Wattier; Robert F T Bucayu; Craig L K Boge; Rachael K Ross; Inci Yildirim; Theoklis E Zaoutis; Debra L Palazzi; Surabhi B Vora; Elio Castagnola; Martha Avilés-Robles; Lara Danziger-Isakov; Alison C Tribble; Tanvi S Sharma; Antonio C Arrieta; Gabriela Maron; David M Berman; Dwight E Yin; Lillian Sung; Michael Green; Emmanuel Roilides; Kiran Belani; José Romero; Pere Soler-Palacin; Eduardo López-Medina; Dawn Nolt; Ibrahim Zaid Bin Hussain; William J Muller; Sarmistha B Hauger; Natasha Halasa; Daniel Dulek; Alice Pong; Blanca E Gonzalez; Mark J Abzug; Fabianne Carlesse; Anna R Huppler; Sujatha Rajan; Catherine Aftandilian; Monica I Ardura; Arunaloke Chakrabarti; Benjamin Hanisch; Christine M Salvatore; Lena Klingspor; Elizabeth D Knackstedt; Irja Lutsar; Maria E Santolaya; Sydney Shuster; Sarah K Johnson; William J Steinbach; Brian T Fisher

doi:10.1093/jpids/piad057

Adjunctive Diagnostic Studies Completed Following Detection of Candidemia in Children: Secondary Analysis of Observed Practice From a Multicenter Cohort Study Conducted by the Pediatric Fungal Network

J Pediatric Infect Dis Soc. 2023 Sep 27;12(9):487-495. doi: 10.1093/jpids/piad057.

Authors

Rachel L Wattier¹, Robert F T Bucayu¹, Craig L K Boge², Rachael K Ross³, Inci Yildirim^{4

5

6

7}, Theoklis E Zaoutis², Debra L Palazzi⁸, Surabhi B Vora⁹, Elio Castagnola¹⁰, Martha Avilés-Robles¹¹, Lara Danziger-Isakov¹², Alison C Tribble¹³, Tanvi S Sharma¹⁴, Antonio C Arrieta^{15

16}, Gabriela Maron¹⁷, David M Berman¹⁸, Dwight E Yin¹⁹, Lillian Sung²⁰, Michael Green²¹, Emmanuel Roilides²², Kiran Belani²³, José Romero²⁴, Pere Soler-Palacin²⁵, Eduardo López-Medina²⁶, Dawn Nolt²⁷, Ibrahim Zaid Bin Hussain²⁸, William J Muller²⁹, Sarmistha B Hauger³⁰, Natasha Halasa³¹, Daniel Dulek³¹, Alice Pong³², Blanca E Gonzalez³³, Mark J Abzug³⁴, Fabianne Carlesse³⁵, Anna R Huppler³⁶, Sujatha Rajan³⁷, Catherine Aftandilian³⁸, Monica I Ardura³⁹, Arunaloke Chakrabarti⁴⁰, Benjamin Hanisch⁴¹, Christine M Salvatore⁴², Lena Klingspor⁴³, Elizabeth D Knackstedt⁴⁴, Irja Lutsar⁴⁵, Maria E Santolaya⁴⁶, Sydney Shuster², Sarah K Johnson⁴⁷, William J Steinbach⁴⁷, Brian T Fisher^{2

48}

Affiliations

¹ Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.
² Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
³ Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, USA.
⁴ Department of Pediatrics, Yale University School of Medicine, Connecticut, USA.
⁵ Yale Institute for Global Health, Yale University, New Haven, Connecticut, USA.
⁶ Yale Center for Infection and Immunity, New Haven, Connecticut, USA.
⁷ Department of Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA.
⁸ Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.
⁹ Department of Pediatrics, University of Washington, Division of Infectious Diseases, Seattle Children's Hospital, Seattle, Washington, USA.
¹⁰ Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
¹¹ Department of Infectious Diseases, Hospital Infantil de México Federico Gómez, Mexico City, Mexico.
¹² Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA.
¹³ Division of Infectious Diseases, Department of Pediatrics, University of Michigan and C.S. Mott Children's Hospital, Ann Arbor, Michigan, USA.
¹⁴ Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹⁵ Department of Infectious Diseases, Children's Hospital of Orange County, Orange, California, USA.
¹⁶ Department of Pediatrics, University of California Irvine, Irvine, California, USA.
¹⁷ Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
¹⁸ Division of Pediatric Infectious Diseases, Johns Hopkins All Children's Hospital, St. Petersburg, Florida, USA.
¹⁹ Department of Pediatrics, Children's Mercy and University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA.
²⁰ Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Canada.
²¹ Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
²² Infectious Diseases Unit, 3rd Department of Pediatrics, Aristotle University and Hippokration Hospital, Thessaloniki, Greece.
²³ Pediatric Infectious Diseases, Children's Minnesota, Minneapolis, Minnesota, USA.
²⁴ National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
²⁵ Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain.
²⁶ Centro de Estudios en Infectología Pediátrica, Clínica Imbanaco Grupo Quirónsalud and Universidad del Valle, Cali, Colombia.
²⁷ Department of Pediatrics, Oregon Health and Science University and Doernbecher Children's Hospital, Portland, Oregon, USA.
²⁸ Pediatric Infectious Diseases, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
²⁹ Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
³⁰ Department of Pediatrics, University of Texas at Austin and Dell Children's Medical Center, Austin, Texas, USA.
³¹ Department of Pediatrics, Vanderbilt University Medical Center and Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.
³² Department of Pediatrics, University of California San Diego and Rady Children's Hospital San Diego, San Diego, California, USA.
³³ Center for Pediatric Infectious Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
³⁴ Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA.
³⁵ Instituto de Oncologia Pediatrica-IOP/GRAACC-UNIFESP, São Paulo, Brazil.
³⁶ Department of Pediatrics, Medical College of Wisconsin and Children's Wisconsin, Milwaukee, Wisconsin, USA.
³⁷ Division of Pediatric Infectious Diseases, Cohen Children's Medical Center, New Hyde Park, New York, USA.
³⁸ Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California, USA.
³⁹ Division of Infectious Diseases and Host Defense Program, Department of Pediatrics, Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio, USA.
⁴⁰ Doodhadhar Burfani Hospital and Research Institute, Haridwar, India.
⁴¹ Pediatric Infectious Diseases, Children's National Health System, Washington, District of Columbia, USA.
⁴² Division of Pediatric Infectious Diseases, Weill Cornell Medicine and Komansky Children's Hospital, New York, New York, USA.
⁴³ Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden.
⁴⁴ Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA.
⁴⁵ Department of Microbiology, University of Tartu, Tartu, Estonia.
⁴⁶ Hospital Dr. Luis Calvo Mackenna, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
⁴⁷ Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
⁴⁸ Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Abstract

Background: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown.

Methods: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression.

Results: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%).

Conclusions: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.

Keywords: candidemia; endocarditis; endophthalmitis; invasive candidiasis; pediatrics.

© The Author(s) 2023. 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.

Publication types

Multicenter Study

MeSH terms

Aged, 80 and over
Antifungal Agents / therapeutic use
Candidemia* / diagnosis
Candidemia* / microbiology
Candidiasis, Invasive* / drug therapy
Child
Cohort Studies
Humans
Logistic Models
Risk Factors

Substances

Antifungal Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding