Improving Antibiotic Stewardship among Asymptomatic Newborns Using the Early-onset Sepsis Risk Calculator.

INTRODUCTION: Neonatologists have long struggled with identifying and treating early-onset sepsis (EOS) without overexposing newborns to unnecessary antibiotics. METHODS: In January 2016, we instituted an EOS protocol based mainly on the 2012 AAP guidelines. We subsequently conducted 2 additional plan-do-study-act cycles to decrease antibiotic usage by integrating the EOS risk calculator into our algorithm. For the periods January 2016-June 2017 (period 1), June 2017-February 2018 (period 2), and February 2018-December 2018 (period 3), we tracked all asymptomatic newborns older than 36 weeks, including those admitted to the neonatal intensive care unit for evaluation of EOS. We monitored the monthly variation in asymptomatic newborns older than 36 weeks who received antibiotics using statistical process control. The number of asymptomatic infants treated with antibiotics during the 3 periods was analyzed. Pairwise comparisons were made using post hoc chi-square analysis. RESULTS: The addition of the EOS calculator score to our guidelines reduced the number of asymptomatic infants older than 36 weeks treated with antibiotics by 73% (P < 0.0001). Adopting the EOS calculator score after clinical examination further reduced the number of infants treated by 89% (P < 0.0001). For period 1, the percentage of asymptomatic infants older than 36 weeks treated with antibiotics was 4.3%; for period 2, it was 1.16%, and for period 3, it was 0.12% (P < 0.0001). CONCLUSIONS: The addition of the EOS calculator score to our AAP-based guidelines reduced antibiotic use among asymptomatic infants older than 36 weeks by 73%. Further adoption of the EOS calculator score after the clinical examination enabled our team to defer antibiotics in almost all asymptomatic infants safely.

Differential effect of exogenous interleukin-10 versus glucocorticoids on gene expression and pro-inflammatory cytokine release by polymorphonuclear leukocytes and monocytes of the newly born.

Bronchopulmonary dysplasia (BPD) is one of the most common causes of mortality and morbidity in neonatal intensive care units. Persistent inflammation, with an abnormal influx of polymorphonuclear leukocytes (PMNs) followed by monocytes (MONOs), occurs early in the pathogenesis of BPD. Anti-inflammatory therapy with better efficacy and safety than dexamethasone (DEX) is needed. In the present study we determined cell-specific gene expression and cytokine release in response to glucocorticoids versus interleukin-10 (IL-10). Subsequently, we hypothesized that the insensitivity of MONOs to DEX was associated with a failure of the glucocorticoid receptor to translocate to the nucleus. PMNs and MONOs were isolated from umbilical cord blood at birth, and pretreated with PBS vehicle, IL-10 or glucocorticoids prior to endotoxin (LPS)-stimulation for 4 and 18h. Genome-wide gene expressions were determined by microarray and validated by RT-qPCR. Interleukin 8 release in cell culture supernatant was measured by ELISA. To examine the mechanism of monocyte insensitivity to glucocorticoids, nuclear translocation of the glucocorticoid receptor was determined by Western blots. MONOs had 6 times the number of genes changing expression with IL-10 compared to PMNs at 4h. DEX at the therapeutic level for neonates with BPD had no effect on gene expression in MONOs. The order of potency for inhibition of interleukin-8 release from MONOs was IL-10 >betamethasone >dexamethasone and hydrocortisone. Glucocorticoid potency in MONOs was directly related to glucocorticoid receptor translocation to nucleus. Gene expression profiling for IL-10 versus glucocorticoids indicates there may be major differences in therapeutic efficacy for BPD.