Late-onset-sepsis Evaluation and Empiric Therapy in Extremely Low Gestational Age Newborns

Background: Over the past two decades late-onset-sepsis (LOS) has decreased in the preterm population in high resource countries, yet it continues to be a substantial cause of morbidity and mortality, especially among extremely low gestational age newborns (ELGANs, gestational age (GA) ≤28 weeks). Timely diagnosis and empiric treatment are associated with reduction in mortality. Little is known about the evaluation process for LOS in ELGANs. The objective of this study is to define the current frequency of LOS evaluation in ELGANs and characterize empiric therapy.

Methods: We conducted a cohort study of ELGANs discharged from >400 Pediatrix Medical Group neonatal intensive care units (NICUs) from 2009 to 2018, excluding infants with congenital anomalies, discharged or deceased prior to postnatal day (PND) 2, or admitted after PND 2. LOS evaluation was defined as blood culture obtained after PND 2, ≥1 day following a negative culture, and ≥10 days from a positive culture. We determined the number of LOS evaluations and percentage positive by gestational age and center. We also evaluated the percentage of infants started on empiric antimicrobials at the time of evaluation. Descriptive and comparative statistics were calculated for each aim using Wilcoxon rank sum, Fisher’s exact, or Pearson chi square testing as appropriate.

Results: Of 47,187 included infants, 31,457 (67%) had ≥1 LOS evaluation and 6720 (21%) had ≥1 LOS episode. The mean number of LOS evaluations per infant was 1.6, and 10% of LOS evaluations were positive. The percentage of infants evaluated for and positive for LOS was higher at earlier GA (Table 1). The range of mean number of evaluations per infant by center varied from 1.3 to 3.9, with a range of percentage positive from 0% to 24%. The greatest number of sepsis evaluations occurred on PND 7. A maximum of 16% positivity occurred on PND 10 and declined with increasing postnatal age (Figure 1). Compared to negative evaluations, positive evaluations were more likely to occur with infants on inotrope support (15% vs 9%; P<0.001) and receiving invasive mechanical ventilation (66% vs 51%; P<0.001). A higher percentage of infants with positive LOS evaluations were started on empiric antimicrobials compared to infants with negative cultures (95% vs 73%; P<0.001). Likewise, more empiric antifungal use occurred in positive evaluations (27% vs 19%; P<0.001). The most prevalent empiric antimicrobial choices were vancomycin (51%), gentamicin (48%), fluconazole (18%), and ampicillin (14%).

Conclusion: Among ELGANs, earlier GA and postnatal age were associated with LOS evaluation and positive cultures. The majority of infants undergoing evaluation for LOS were started on empiric antibiotics. Additional studies are needed to evaluate efficacy and utility of current practices for LOS evaluation and empiric treatment.