Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants.
OBJECTIVE
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 (> or =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.


CONCLUSIONS
Prolonged initial empirical antibiotic therapy may be associated with increased risk of necrotizing enterocolitis or death and should be used with caution.
Cotten
C Michael
CM
Department of Pediatrics, Duke University, Durham, NC 27710, USA. cotte010@mc.duke.edu
Taylor
Sarah
S
Stoll
Barbara
B
Goldberg
Ronald N
RN
Hansen
Nellie I
NI
Sánchez
Pablo J
PJ
Ambalavanan
Namasivayam
N
Benjamin
Daniel K
DK
D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D004334:Drug Administration Schedule; D036262:Empirical Research; D020345:Enterocolitis, Necrotizing / Q000139:chemically induced* / Q000401:mortality*; D006801:Humans; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000139:chemically induced* / Q000401:mortality*; D009026:Mortality / Q000639:trends; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors
D000900:Anti-Bacterial Agents