Outcomes and antimicrobial usage in preterm neonates < 34 weeks gestation with culture-negative neonatal sepsis: a prospective observational study

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BACKGROUND: Culture-negative sepsis (CNNS) constitutes a significant proportion of neonates admitted to the NICU. However, the outcomes and factors influencing antimicrobial therapy in this group remain understudied. METHODS: We prospectively enrolled preterm neonates (<34 weeks' gestation) with clinical features of sepsis, with or without sepsis screen positive results. Primary outcome was a composite of death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity requiring treatment, Intraventricular haemorrhage ≥ 2 and periventricular leukomalacia. Details of antimicrobial therapy were also collected. RESULTS: Over an 18-month period, 172 neonates were enrolled. 104 had CNNS and 68 had culture-positive sepsis (CPNS). Primary outcome was observed in 19 (18.3%) neonates with CNNS and 25 (36.8%) with CPNS, with an adjusted odds ratio (aOR) of 0.50 (95% CI: 0.22-1.12, p = 0.095). Except for BPD, which was significantly lower in CNNS (aOR: 0.10; 95% CI: 0.02-0.52, p = 0.006), there was no statistically significant difference in other outcomes between groups. Multidrug-resistant organisms comprised 67.6% of the gram-negative bacterial isolates. Median (IQR) cumulative duration of antibiotic therapy was 5 (3-7) days in CNNS and 20.5 (15-24.3) days in CPNS. Prolonged cumulative antibiotic use was observed in 50 (48%) CNNS neonates (>5 days) and 50 (73.5%) CPNS neonates (>14 days). In CNNS group, 38 (36.5%) received second-line antibiotics, and 6 (5.7%) received third-line antibiotics. CONCLUSION: In preterm neonates, composite outcome of mortality and major morbidities did not differ significantly between those with CNNS and CPNS. However, a considerable proportion of CNNS neonates received a prolonged course of higher antibiotics. Thus, there is a need for strategies to improve clinical outcomes and strengthen adherence to antibiotic stewardship principles.

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