560 - Late Antibiotic Use Among Preterm Infants Admitted to the Neonatal Intensive Care Unit

Publication Number: 560.5629

Sarah A. Coggins, University of Pennsylvania/Children's Hospital of Philadelphia, Philadelphia, PA, United States; Alvaro Zevallos Barboza, Childrens Hospital of Philadelphia, Arlington, VA, United States; Karen M. Puopolo, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Dustin D. Flannery, Childrens Hospital of Philadelphia, Philadelphia, PA, United States

Background: Clinical guidance for empiric antibiotic choice is a key tenet of antibiotic stewardship. Evidence-based guidance exists for neonatal early-onset sepsis but no consensus recommendations direct empiric antibiotic choice for late-onset sepsis risk among preterm infants in the NICU.

Objective: To describe empiric antibiotic selection and utilization patterns after 3 days of age among a large sample of preterm infants admitted to NICUs across the US over 15 years.

Design/Methods: Retrospective cross-sectional study using the Premier Health Database of inborn infants ≤34 weeks’ gestation admitted to a NICU >3 days from 2009-23. A late antibiotic course was defined as initiation of parenteral antibiotic(s) at ≥4 days of age. To account for multiple late courses, a new course was defined if antibiotics were re-initiated after ≥3 consecutive antibiotic-free days. A late antibiotic regimen was defined as antibiotic(s) given on the first day of each course. Antibiotics initiated on days 1-3 of age and continued past day 4 were excluded. Analyses included descriptive statistics and proportional trend analysis.

Results: Among 420,687 preterm infants admitted to 699 NICUs for >3 days, 65,398 (15.5%) were administered 108,268 late courses. Infants were administered 49 different late antibiotics; gentamicin (10.1%), vancomycin (9.7%), ampicillin (5%), cefazolin (2.3%) and piperacillin/tazobactam (2.1%) were the most common infant exposures. The proportion of infants with any late antibiotic exposure declined from 18.2% in 2009 to 16.0% in 2023 (p < 0.001). There were 1012 unique regimens administered; Table 1 shows the 20 most common regimens, accounting for 81% of all courses. Vancomycin was a component of 10/20 most common regimens but proportional use of vancomycin-containing regimens declined from 50.9% of all courses in 2009-13 to 30.6% in 2021-23 (p < 0.001). Between 2009-13 and 2021-23, use of nafcillin or oxacillin-containing regimens (5.1% to 11.6%) and use of piperacillin/tazobactam or cefepime-containing regimens (4.0% to 16.1%) increased (p < 0.001, Fig 1). Proportional changes in late antibiotic use were noted over the NICU care course (Fig 2), with cefazolin the dominant exposure after 90 days of age.

Conclusion(s): In this study across 700 NICUs over 15 years, we show significant changes in late antibiotic exposure rates and empiric antibiotic choices. Wide variation in antibiotic use emphasizes the need for late stewardship guidance. Further study is needed to determine the impact of patient-mix and clinical indication on late antibiotic use to ensure appropriate drug-bug match in recommended empiric regimens.

Table 1: Late Antibiotic Regimen Utilization, 2009-2023
Footnote: Denominator (N) reflects all unique late antibiotic courses. Among 1,012 unique antibiotic regimens identified; table includes the 20 most prevalent over the study period; these 20 regimens accounted for 81% of the total empiric antibiotic courses.

Figure 1: Late Antibiotic Regimen Use over the Study Period
Footnote: "2009" represents the 2009-12 epoch; "2013" represents the 2013-16 epoch; "2017" represents the 2017-20 epoch; "2021" represents the 2021-23 epoch.

Figure 2: Distribution of late antibiotic regimen use over the NICU hospitalization
Footnote: Time periods included the following number of patients: Days 4-30, N=62,678; Days 31-60, N=23,912; Days 61-90, N=10,796; Days 91-120, N=5228; Days 121+, N=5684

Table 1: Late Antibiotic Regimen Utilization, 2009-2023
Footnote: Denominator (N) reflects all unique late antibiotic courses. Among 1,012 unique antibiotic regimens identified; table includes the 20 most prevalent over the study period; these 20 regimens accounted for 81% of the total empiric antibiotic courses.

Figure 1: Late Antibiotic Regimen Use over the Study Period
Footnote: "2009" represents the 2009-12 epoch; "2013" represents the 2013-16 epoch; "2017" represents the 2017-20 epoch; "2021" represents the 2021-23 epoch.

Figure 2: Distribution of late antibiotic regimen use over the NICU hospitalization
Footnote: Time periods included the following number of patients: Days 4-30, N=62,678; Days 31-60, N=23,912; Days 61-90, N=10,796; Days 91-120, N=5228; Days 121+, N=5684