Antibiotic Therapy in Patients with Necrotizing Enterocolitis in the Neonatal Intensive Care Unit: A Quality Improvement Project

Background: Broad-spectrum antibiotics (abx) are used for treatment of necrotizing enterocolitis (NEC) in neonates. However, there are no guidelines for empiric treatment or length of therapy (LOT). Overutilization of broad-spectrum abx is known to increase resistance. The new IDSA stewardship guidelines support focusing on specific infectious disease syndromes to improve abx use. The purpose was to evaluate abx regimens given to neonates with NEC to assess optimal duration of therapy needed for treatment.

Methods: A retrospective analysis of patients diagnosed with NEC (Bell Stage 2 or higher) from 2007 to 2014 at Arkansas Children’s Hospital was performed. Patients with gastroschisis, encephalocele, congenital heart defects, and/or ≤ 7 days of abx therapy were excluded. Neonates with non-surgical NEC (ns-NEC) and surgical NEC (s-NEC) were compared. For LOT, patients were classified into 3 groups: 8-10 days, 11-14 days, and >14 days of abx therapy. Group comparisons were done using Fisher’s exact test, 2-sample t-test, or one-way ANOVA.

Results: 187 patients with NEC were identified with 45 patients excluded. 65 neonates had ns-NEC and 77 had s-NEC. More than 12 different empiric abx combinations were utilized. Vancomycin was given in 89% of ns-NEC and 82% of s-NEC. The most frequent gram-negative abx was piperacillin/tazobactam; in 60% of ns-NEC and 44% of s-NEC cases. Triple antimicrobial regimens were used in 9% of ns-NEC and 48% of s-NEC cases. Empiric regimens were not de-escalated in 55% of ns-NEC and 38% of s-NEC cases. No differences were seen in patient outcomes between ns-NEC and s-NEC cases: parenteral nutrition complications (P = 0.41 and P = 0.18), intestinal stricture (P = 0.67 and P = 0.59), neurodevelopmental disabilities (P = 0.45 and P = 0.90), and mortality (P = 0.26 and P = 0.56). A sub-analysis of neonates with positive bacterial cultures, 5 in ns-NEC and 38 in s-NEC, showed no difference in patient outcomes.

Conclusion: This study supports using a shorter LOT, of 8-10 days, in neonates with ns-NEC or s-NEC, even in the setting of a positive bacterial culture, and de-escalating abx therapy in culture negative patients. Given the varied broad-spectrum abx regimens used for empiric therapy, we also suggest future studies to determine the best empiric regimen for neonatal NEC.