Temporal Trends and Center Variation in Early Antibiotic Use Among Premature Infants
Authors: Dustin D. Flannery, Rachael K. Ross, Sagori Mukhopadhyay, Alison C. Tribble, Karen M. Puopolo, Jeffrey S. Gerber
Journal: JAMA Network Open (2018)

<h3>Importance</h3> Premature infants are frequently administered empirical antibiotic therapy at birth. Early and prolonged antibiotic exposures among infants without culture-confirmed infection have been associated with increased risk of adverse outcomes. <h3>Objective</h3> To examine early antibiotic use among premature infants over time and across hospitals in the United States. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used a comprehensive administrative database of inpatient encounters from 297 academic and community hospitals across the United States to examine data concerning very low-birth-weight (VLBW) infants (&lt;1500 g), including extremely low-birth-weight (ELBW) infants (&lt;1000 g), who were admitted to the neonatal intensive care unit and survived for at least 1 day. Data collection took place in November 2015 and analysis took place from February 2016 to November 2016. <h3>Exposures</h3> Antibiotic initiation within the first 3 days of age and subsequent antibiotic administration for more than 5 days. <h3>Main Outcomes and Measures</h3> Temporal trends in early antibiotic initiation and duration from 2009 to 2015, and center variation in early antibiotic use from 2014 to 2015. <h3>Results</h3> We identified 40 364 VLBW infants (20 447 female [50.7%]) who survived for at least 1 day, including 12 947 ELBW infants, from 297 centers. The majority of premature infants had early antibiotic initiation (31 715 VLBW infants [78.6%] and 11 264 ELBW infants [87.0%]), and no differences were observed over time in temporal trend analyses (<i>P</i> = .12 for VLBW and<i>P</i> = .52 for ELBW). The annual risk difference in the proportion of VLBW infants administered early antibiotic therapy ranged from −0.75% (95% CI, −1.61% to 0.11%) to −0.87% (95% CI, −2.04% to 0.30%); in ELBW infants the annual risk difference ranged from −0.34% (95% CI, −1.28% to 0.61%) to −0.38% (95% CI, −1.61% to 0.85%). There was a small but significant decrease over time in the rate of prolonged antibiotic duration for VLBW infants (<i>P</i> = .02), but not for ELBW infants (<i>P</i> = .22). The annual risk difference in the proportion of VLBW infants with prolonged antibiotic duration ranged from −0.94% (95% CI, −1.65% to −0.23%) to −1.08% (95% CI, −2.00% to −0.16%); in ELBW infants the annual risk difference ranged from −0.72% (95% CI, −1.83% to 0.39%) to −0.75% (95% CI, −1.96% to 0.46%). We also observed variation in early antibiotic exposures across centers. Sixty-nine of 113 centers (61.1%) started antibiotic therapy for more than 75% of VLBW infants, and 56 of 66 centers (84.8%) started antibiotic therapy for more than 75% of ELBW infants. The proportion of VLBW and ELBW infants administered prolonged antibiotics ranged from 0% to 80.4% and 0% to 92.0% across centers, respectively. <h3>Conclusions and Relevance</h3> Most premature infants in this study received empirical early antibiotic therapy with little change over a recent 7-year period. The variability in exposure rates across centers, however, suggests that neonatal antimicrobial stewardship efforts are warranted to optimize antibiotic use for VLBW and ELBW infants.