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PEDIATRICS Vol. 112 No. 3 September 2003, pp. 543-547

Empirical Therapy for Neonatal Candidemia in Very Low Birth Weight Infants

Daniel K. Benjamin, Jr, MD, MPH, PhD*,{ddagger}, Elizabeth R. DeLong, PhD*, William J. Steinbach, MD{ddagger},§,||, Charles M. Cotton, MD{ddagger}, Thomas J. Walsh, MD and Reese H. Clark, MD#

* Department of Pediatrics, Duke University, Durham, North Carolina
{ddagger} Duke University Clinical Research Institute, Durham, North Carolina
§ Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina
|| Duke University Mycology Research Unit, Durham, North Carolina
National Cancer Institute, Bethesda, Maryland
# Pediatrix Medical Group, Inc, Jacksonville, Florida

Objective. Neonatal candidemia is often fatal. Empirical antifungal therapy is associated with improved survival in neonates and patients with fever and neutropenia. Although guidelines for empirical therapy exist for patients with fever and neutropenia, these do not exist for neonates.

Methods. A multicenter, retrospective, cohort study was conducted of neonatal intensive care unit patients (N = 6172) who had a blood culture (N = 21 233) after day of life 3 and whose birth weight was ≤1250 g. We performed multivariable conditional logistic regression of risk factors for candidemia. From the regression modeling coefficients, we developed a candidemia score.

Results. In multivariable modeling, thrombocytopenia (odds ratio [OR]: 3.56; 95% confidence interval [CI]: 2.68–4.74) and cephalosporin or carbapenem use in the 7 days before obtaining the blood culture (OR: 1.77; 95% CI: 1.33–2.29) were risk factors for subsequent candidemia. Children who were 25 to 27 weeks’ estimated gestational age (OR: 2.02; 95% CI: 1.52–3.05) and children who were born at <25 weeks (OR: 4.15; 95% CI: 3.12–6.29) were at higher risk of developing candidemia than were children who were born at ≥28 weeks. We developed a candidemia score on the basis of the ORs from the multivariable model. Children with a candidemia score ≥2 points were classified as having a "positive" score, and a score of ≥2 points had a sensitivity of 85% and a specificity of 47%.

Conclusions. We developed a clinical predictive model for neonatal candidemia with high sensitivity and moderate specificity for candidemia. On the basis of our model, when a physician obtains a blood culture, the physician should consider providing antifungal therapy to neonates who are <25 weeks’ estimated gestational age and to neonates who have thrombocytopenia at the time of blood culture. In addition, if a physician obtains a blood culture from a child who is 25 to 27 weeks’ estimated gestational age and is not thrombocytopenic but has a history of third-generation cephalosporin or carbapenem exposure in the 7 days before the blood culture, then the physician should consider administration of empirical antifungal therapy.

Key Words: invasive candidiasis • prophylaxis • positive predictive value

Abbreviations: NICU, neonatal intensive care unit • ELBW, extremely low birth weight • EGA, estimated gestational age • CI, confidence interval • OR, odds ratio

Received for publication Dec 19, 2002; Accepted Mar 6, 2003.




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