Empiric use of ampicillin and cefotaxime, compared with ampicillin and gentamicin, for neonates at risk for sepsis is associated with an increased risk of neonatal death.
BACKGROUND
We reported previously that the use of cephalosporin among premature neonates increased the risk of subsequent fungal sepsis. As a result, we recommended that ampicillin and gentamicin be used as empiric coverage for early-onset neonatal sepsis while culture results are awaited.


OBJECTIVE
To describe antibiotic use during the first 3 days after birth for neonates admitted to the NICU and to evaluate the outcomes for neonates treated with 2 different antibiotic regimens.


METHODS
We assembled a cohort of inborn neonates, from our deidentified administrative database, who had documented exposure to ampicillin during the first 3 days after birth. Infants treated concurrently with cefotaxime or gentamicin were evaluated, to identify the factors that were associated independently with death before discharge, with both univariate and multivariate analyses.


RESULTS
There were 128,914 neonates selected as the study cohort; 24,111 were treated concurrently with ampicillin and cefotaxime and 104,803 were treated concurrently with ampicillin and gentamicin. Logistic modeling showed that neonates treated with ampicillin/cefotaxime were more likely to die (adjusted odds ratio: 1.5; 95% confidence interval: 1.4-1.7) and were less likely to be discharged to home or foster care than were neonates treated with ampicillin/gentamicin. This observation was true across all estimated gestational ages. Other factors that were associated independently with death included immature gestational age, need for assisted ventilation on the day of admission to the NICU, indications of perinatal asphyxia or major congenital anomaly, and reported use of ampicillin/cefotaxime.


CONCLUSIONS
For patients receiving ampicillin, the concurrent use of cefotaxime during the first 3 days after birth either is a surrogate for an unrecognized factor or is itself associated with an increased risk of death, compared with the concurrent use of gentamicin.
Clark
Reese H
RH
Pediatrix-Obstetrix Center for Research and Education, Sunrise, Florida, USA. reese_clark@pediatrix.com
Bloom
Barry T
BT
Spitzer
Alan R
AR
Gerstmann
Dale R
DR
D000667:Ampicillin / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D002439:Cefotaxime / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005839:Gentamicins / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007226:Infant Mortality; D007231:Infant, Newborn; D012307:Risk Factors; D018805:Sepsis / Q000517:prevention & control*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D000667:Ampicillin; D002439:Cefotaxime