Variations in Neonatal Antibiotic Use

Abstract

OBJECTIVES: We sought to identify whether and how the NICU antibiotic use rate (AUR), clinical correlates, and practice variation changed between 2013 and 2016 and attempted to identify AUR ranges that are consistent with objectively determined bacterial and/or fungal disease burdens. METHODS: In a retrospective cohort study of >54000 neonates annually at >130 California NICUs from 2013 to 2016, we computed nonparametric linear correlation and compared AURs among years using a 2-sample test of proportions. We stratified by level of NICU care and participation in externally organized stewardship efforts. RESULTS: By 2016, the overall AUR declined 21.9% (95% confidence interval [CI] 21.9%–22.0%), reflecting 42960 fewer antibiotic days. Among NICUs in externally organized antibiotic stewardship efforts, the AUR declined 28.7% (95% CI 28.6%–28.8%) compared with 16.2% (95% CI 16.1%–16.2%) among others. The intermediate NICU AUR range narrowed, but the distribution of values did not shift toward lower values as it did for other levels of care. The 2016 AUR correlated neither with proven infection nor necrotizing enterocolitis. The 2016 regional NICU AUR correlated with surgical volume (ρ = 0.53; P = .01), mortality rate (ρ = 0.57; P = .004), and average length of stay (ρ = 0.62; P = .002) and was driven by 3 NICUs with the highest AUR values (30%–57%). CONCLUSIONS: Unexplained antibiotic use has declined but continues. Currently measured clinical correlates generally do not help explain AUR values that are above the lowest quartile cutpoint of 14.4%.

Understanding the impact of antibiotic perturbation on the human microbiome

“…Antibiotic treatment decreases gut microbial diversity and enriches for AR potential pathogens [54]. Antibiotics delivered in the NICU are varied, [63] ranging from relatively shortterm exposure with narrow-spectrum agents such as ampicillin or cefazolin to long-term exposure with broad-spectrum agents such as 3rd-generation cephalosporins and carbapenems [54,64]. The preterm gut microbiota of NICU-hospitalized neonates is dominated by Escherichia coli, Klebsiella spp., Enterobacter spp., and Enterococcus spp., which are found in the NICU environment, are often multi-drug resistant, and are causes of bacteremia in this population [54,65,66] ( Table 2).…”

Challenges and opportunities for antibiotic stewardship among preterm infants

“…Decreases in overall neonatal antibiotic utilisation are reported in conjunction with multiple antimicrobial stewardship interventions25–27 and among term infants with use of multivariate risk models for EOS risk assessment 28 29. Schulman et al recently reported a significant decrease in antibiotic use rate of 21.9% in ~130 NICUs across California from 2013 to 2 016 30. They found a greater reduction in centres participating in study-defined antibiotic stewardship efforts compared with centres without such participation (28.7% vs 16.2%) underscoring the importance of stewardship efforts.…”

“…A final use of biomarkers may be to determine length of therapy for conditions in which antibiotic use in mandated. Hemels et al 59 observed that most CONS bacteraemia at their centre resolved within 72 hours of antibiotic initiation when the infants demonstrated clinical improvement, CRP levels decreased and central catheters were removed 30. This group later reported an observational experience of treating infants meeting such criteria with 3 or 7 days of antibiotics, and found no difference in resolution of bacteraemia or clinical outcome 59.…”

Approaches to Dose Finding in Neonates, Illustrating the Variability between Neonatal Drug Development Programs

“…The use of chloramphenicol with the associated grey baby syndrome is a historical illustration of potentially relevant toxicity, while inadequate dosing may result in therapeutic failure. Off-label use has the potential to result in inadequate or inaccurate dosing and explains the variations in dosing regimens for antibiotics in both US as well as European neonatal intensive care units [19,20].…”