Early Diagnosis of Candidiasis in Premature Infants

Study Overview
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Brief Summary
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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
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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.

Official Title
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Early Diagnosis of Nosocomial Candidiasis Study

Conditions
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Infection, Candida, Candidiasis, Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants born ≤1,000g birth weight Infants >72 hours old and less than 120 days old Exclusion Criteria: Prior positive blood culture for Candida Evidence of congenital candidiasis Parents/legal guardians refuse consent

Ages Eligible for Study
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Minimum Age: 3 Days
Maximum Age: 120 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of invasive candidiasis based on new assay results |  | Until discharge | 
| Determine test performance of clinical predictive model |  | Until discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 blood culture |  | 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 | 
| Determine test performance of urine cultures |  | 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 resistance patterns of organisms isolated |  | Until discharge | 
| Determine molecular epidemiology of candidemia |  | Until discharge | 
| Determine genetic expression of organism virulence factors |  | Until discharge | 
| Neurodevelopmental outcome |  | 18-22 months corrected age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NICHD Neonatal Research Network, Fungal Infection, Mycosis, Extremely Low Birth Weight (ELBW), Prematurity, Clinical Judgement, Polymerase chain reaction (PCR) testing, Beta-glucan assay, Mass Spectrometry, Lumbar puncture