Duration of Therapy for Culture-Negative Sepsis in a Neonatal Intensive Care Unit

Corresponding Author Darra Drucker, PharmD, Department of Pharmacy, Children's Hospital Los Angeles, 4650 Sunset Blvd., MS#51, Los Angeles, CA 90027, USA, (323) 208-1707, ddrucker@chla.usc.edu Funding No external funding. Conflict(s) of Interest Darra Drucker, no conflict; Regina Orbach, no conflict; Trang Censon, no conflict; Leila Posch, no conflict. Background Neonatal late onset sepsis (LOS) is associated with high morbidity and mortality, and early initiation of antimicrobial therapy can improve clinical outcomes. However, patient complexity and concern for poor outcomes can lead providers to treat patients with prolonged antibiotics despite negative cultures. Prolonged exposure to antibiotics increases patient risk for adverse effects and can contribute to antimicrobial resistance. In July 2023, Children’s Hospital Los Angeles (CHLA) implemented an updated Neonatal Intensive Care Unit (NICU) LOS guideline in response to an increase in broad-spectrum antibiotic use with a standardized 5-day duration for culture-negative sepsis. The purpose of this study was to evaluate the impact of this quality improvement intervention on broad-spectrum antibiotic use for late onset culture-negative sepsis in the NICU. Methods A retrospective chart review was conducted at CHLA comparing patients in the NICU who received cefepime or ceftazidime for the indication of sepsis in the pre-guideline (January through June 2023) and post-guideline (January through June 2024) implementation periods. Patients were excluded if they received ≤3 days of ceftazidime and/or cefepime or if they were treated for an infection because of culture-positivity. Collected data included days of therapy for ceftazidime and cefepime, microbiological culture results, history of bronchopulmonary dysplasia (BPD), and whether the Infectious Diseases (ID) consult team was involved in the patient’s care. The primary outcome was treatment duration for culture-negative sepsis. Secondary outcomes included percentage of patients treated >6 days and days of therapy of broad-spectrum antibiotics in the NICU. Results Among patients who received empiric antibiotics for sepsis in the NICU, 9 of 67 antibiotic courses were included in the pre-implementation period, and 15 of 75 courses were included in the post-implementation period. After LOS guideline implementation, median duration of treatment decreased from 9 (range 4 to 17; IQR 8 to 9) to 8 days (range 4 to 11 days; IQR 6 to 8). The percentage of patients treated for culture-negative sepsis for >6 days decreased from 89% to 53% after guideline implementation. NICU average antibiotic utilization rate decreased from 343 days of therapy per 1000 patient days in the pre-implementation period to 287 in the post-implementation period. In the post-implementation period, 4 patients had BPD in comparison to no patients in the pre-implementation period. The ID team consulted on 2 patients in both periods. Conclusion The implementation of an updated NICU LOS guideline led to a decrease in median antibiotic duration for treatment of culture-negative sepsis. Additionally, average antibiotic utilization in this patient population decreased after this intervention. However, the significance of these results is limited by a small sample size. Further evaluation is needed to assess the barriers to treating NICU patients with shorter durations of antimicrobial therapy.