Published online December 29, 2008
PEDIATRICS Vol. 123 No. 1 January 2009, pp. 58-66 (doi:10.1542/peds.2007-3423)

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ARTICLE

Prolonged Duration of Initial Empirical Antibiotic Treatment Is Associated With Increased Rates of Necrotizing Enterocolitis and Death for Extremely Low Birth Weight Infants

C. Michael Cotten, MD, MHS^a, Sarah Taylor, BSPH^b, Barbara Stoll, MD^c, Ronald N. Goldberg, MD^a, Nellie I. Hansen, MPH^b, Pablo J. Sánchez, MD^d, Namasivayam Ambalavanan, MD^e, Daniel K. Benjamin, Jr, MD, MPH, PhD^a,f for the NICHD Neonatal Research Network

^a Department of Pediatrics
^f Duke Clinical Research Institute, Duke University, Durham, North Carolina
^b RTI International, Research Triangle Park, North Carolina
^c Department of Pediatrics, Emory University, Atlanta, Georgia
^d Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
^e Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama

OBJECTIVES. Our objectives were to identify factors associated with the duration of the first antibiotic course initiated in the first 3 postnatal days and to assess associations between the duration of the initial antibiotic course and subsequent necrotizing enterocolitis or death in extremely low birth weight infants with sterile initial postnatal culture results.

METHODS. We conducted a retrospective cohort analysis of extremely low birth weight infants admitted to tertiary centers in 1998–2001. We defined initial empirical antibiotic treatment duration as continuous days of antibiotic therapy started in the first 3 postnatal days with sterile culture results. We used descriptive statistics to characterize center practice, bivariate analyses to identify factors associated with prolonged empirical antibiotic therapy (5 days), and multivariate analyses to evaluate associations between therapy duration, prolonged empirical therapy, and subsequent necrotizing enterocolitis or death.

RESULTS. Of 5693 extremely low birth weight infants admitted to 19 centers, 4039 (71%) survived >5 days, received initial empirical antibiotic treatment, and had sterile initial culture results through the first 3 postnatal days. The median therapy duration was 5 days (range: 1–36 days); 2147 infants (53%) received prolonged empirical therapy (center range: 27%–85%). Infants who received prolonged therapy were less mature, had lower Apgar scores, and were more likely to be black. In multivariate analyses adjusted for these factors and center, prolonged therapy was associated with increased odds of necrotizing enterocolitis or death and of death. Each empirical treatment day was associated with increased odds of death, necrotizing enterocolitis, and the composite measure of necrotizing enterocolitis or death.

CONCLUSION. Prolonged initial empirical antibiotic therapy may be associated with increased risk of necrotizing enterocolitis or death and should be used with caution.

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Key Words: antibiotic use • bloodstream infection • extremely low birth weight infants • necrotizing enterocolitis • death

Abbreviations: CI—confidence interval • ELBW—extremely low birth weight • NICHD—Eunice Kennedy Shriver National Institute of Child Health and Human Development • EOS—early-onset sepsis • LOS—late-onset sepsis • NEC—necrotizing enterocolitis • OR—odds ratio

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Accepted Apr 1, 2008.

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