Early Diagnosis of Candidiasis in Premature Infants
- Conditions
- Infant, Low Birth WeightCandidaInfant, Small for Gestational AgeInfant, PrematureInfant, NewbornInfectionCandidiasis
- Registration Number
- NCT00109525
- Lead Sponsor
- NICHD Neonatal Research Network
- Brief Summary
This observational study evaluated the performance of new lab tests in detecting candida species fungal infections in extremely low birth weight (ELBW) infants quickly and accurately. 19 NICHD Neonatal Research Network sites enrolled 1,500 infants with birth weights ≤1,000g; 100 of these infants later tested positive for candidiasis. Blood, urine, and lumbar puncture samples were collected whenever other specimens were obtained from participants for cultures. These samples are being tested using the new methods and compared with standard culture results. Surviving study subjects completed a neurodevelopmental evaluation at 18-22 months corrected age.
- Detailed Description
Candida species are a leading cause of infectious mortality in newborns with the incidence rates estimated at 4-18% in extremely low birth weight (ELBW) infants. 20-30% of these infants are likely to die. Because candida can invade virtually all body tissues (eyes, brain, heart, lung, liver, spleen, urinary tract, and joints), survivors of invasive Candida infections are at risk of blindness, developmental delays, and the need for surgical and other corrective procedures.
Time is of the essence in detecting and treating these infections, with infant mortality from candidiasis largely attributed to duration of time for cultures to become positive for Candida. Diagnosis of candidiasis is challenging - blood and urine tests are slow (taking up to 72 hours to complete) and inaccurate in many cases, showing negative results despite overwhelming disease in adults as well as children. These problems are likely made worse in neonates, with smaller amounts of blood available for testing and infections that often spread to tissues inaccessible for testing.
This observational study is evaluating the performance of new lab tests (beta-glucan assays, Gas Chromatography Mass Spectrometry for D-arabinitol, and polymerase chain reaction tests) compared to existing culture tests in detecting candida species fungal infections in extremely low birth weight (ELBW) infants quickly and accurately.
In this study, 19 NICHD Neonatal Research Network sites enrolled 1,500 infants with birth weights ≤1,000g by 72 hours of life; more than 100 of these infants later tested positive for candidiasis. In the larger cohort, whenever cultures of blood or urine were obtained, or a lumbar puncture was done, additional samples and clinical data were collected. These additional samples are being tested using the new techniques under investigation. No additional blood specimens were taken once participants had a positive blood culture for candida. Note: Test procedure reagents are being provided the Duke University laboratory by Cape Cod Incorporated and Rockeby; the Thrasher Research Fund is also providing support to the Duke University laboratory.
Surviving study subjects completed a neurodevelopmental evaluation at 18-22 months corrected age to evaluate potential early risk factors with long-term outcome.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1500
- Infants born ≤1,000g birth weight
- Infants >72 hours old and less than 120 days old
- Prior positive blood culture for Candida
- Evidence of congenital candidiasis
- Parents/legal guardians refuse consent
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Probability of invasive candidiasis based on new assay results Until discharge Determine test performance of clinical predictive model Until discharge
- Secondary Outcome Measures
Name Time Method Determine test performance of the blood culture Until discharge Determine test performance of urine cultures Until discharge Determine test performance (sensitivity and specificity) of polymerase chain reaction (PCR) testing Until discharge Determine test performance of Beta-glucan assay Until discharge Determine test performance of Gas Chromatography Mass Spectrometry for D-arabinitol of blood samples Until discharge Determine test performance of Gas Chromatography Mass Spectrometry for D-arabinitol of urine samples Until discharge Determine test performance of the lumbar puncture (cell count, protein, glucose, and culture) Until discharge Determine test performance of tracheal aspirates Until discharge Compare clinical predictive model performance to neonatologist clinical judgment Until discharge Determine incidence of end-organ damage in neonates with candidemia Until discharge Determine genetic expression of organism virulence factors Until discharge Neurodevelopmental outcome 18-22 months corrected age Determine molecular epidemiology of candidemia Until discharge Determine resistance patterns of organisms isolated Until discharge
Trial Locations
- Locations (20)
University of New Mexico
🇺🇸Albuquerque, New Mexico, United States
Yale University
🇺🇸New Haven, Connecticut, United States
University of Rochester
🇺🇸Rochester, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Stanford University
🇺🇸Palo Alto, California, United States
University of California at San Diego
🇺🇸San Diego, California, United States
University of Miami
🇺🇸Miami, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Wayne State University
🇺🇸Detroit, Michigan, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Case Western Reserve University, Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Wake Forest University
🇺🇸Charlotte, North Carolina, United States
Cincinnati Children's Medical Center
🇺🇸Cincinnati, Ohio, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Brown University, Women & Infants Hospital of Rhode Island
🇺🇸Providence, Rhode Island, United States
RTI International
🇺🇸Durham, North Carolina, United States