Early Antibiotic Use and Neonatal Outcomes Among Preterm Infants Without Infections

Abstract

OBJECTIVES: To determine whether use, duration, and types of early antibiotics were associated with neonatal outcomes and late antibiotic use in preterm infants without infection-related diseases. METHODS: This cohort study enrolled infants admitted to 25 tertiary NICUs in China within 24 hours of birth during 2015–2018. Death, discharge, or infection-related morbidities within 7 days of birth; major congenital anomalies; and error data on antibiotic use were excluded. The composite outcome was death or adverse morbidities. Late antibiotic use indicated antibiotics used after 7 days of age. Late antibiotic use rate was total antibiotic use days divided by the days of hospital stay after the first 7 days of life. RESULTS: Among 21 540 infants, 18 302 (85.0%) received early antibiotics. Early antibiotics was related to increased bronchopulmonary dysplasia (BPD) (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.05-1.56), late antibiotic use (aOR, 4.64; 95% CI, 4.19-5.14), and late antibiotic use rate (adjusted mean difference, 130 days/1000 patient-days; 95% CI, 112-147). Each additional day of early antibiotics was associated with increased BPD (aOR, 1.07; 95% CI, 1.04-1.10) and late antibiotic use (aOR, 1.41; 95% CI, 1.39-1.43). Broad-spectrum antibiotics showed larger effect size on neonatal outcomes than narrow-spectrum antibiotics. The correlation between early antibiotics and outcomes was significant among noncritical infants but disappeared for critical infants. CONCLUSIONS: Among infants without infection, early antibiotic use was associated with increased risk of BPD and late antibiotic use. Judicious early antibiotic use, especially avoiding prolonged duration and broad-spectrum antibiotics among noncritical infants, may improve neonatal outcomes and overall antibiotic use in NICUs.

Sustaining the Continued Effectiveness of an Antimicrobial Stewardship Program in Preterm Infants

“…Approximately 14% of late preterm and full-term neonates and up to 90% of extremely-low-birth-weight (ELBW) infants receive empirical antibiotics immediately after birth, although culture-proven EOS occurs in only a few of these neonates [ 8 ]. Antibiotic exposure during the first few days of life may have important adverse effects [ 9 , 10 ]. Indeed, early and prolonged exposure to antibiotics may increase the risk of antimicrobial resistance and lead to dysbiosis, with a potential negative impact, especially in preterm infants [ 8 , 9 , 10 ].…”

“…Antibiotic exposure during the first few days of life may have important adverse effects [ 9 , 10 ]. Indeed, early and prolonged exposure to antibiotics may increase the risk of antimicrobial resistance and lead to dysbiosis, with a potential negative impact, especially in preterm infants [ 8 , 9 , 10 ]. Short- and long-term morbidity after antibiotic exposure has been reported in uninfected preterm infants [ 8 , 9 , 10 ].…”

“…Indeed, early and prolonged exposure to antibiotics may increase the risk of antimicrobial resistance and lead to dysbiosis, with a potential negative impact, especially in preterm infants [ 8 , 9 , 10 ]. Short- and long-term morbidity after antibiotic exposure has been reported in uninfected preterm infants [ 8 , 9 , 10 ]. For example, early and prolonged administration of antibiotics has been associated with an increased risk of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), invasive candidiasis, and death [ 9 , 10 ].…”

“…Short- and long-term morbidity after antibiotic exposure has been reported in uninfected preterm infants [ 8 , 9 , 10 ]. For example, early and prolonged administration of antibiotics has been associated with an increased risk of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), invasive candidiasis, and death [ 9 , 10 ]. Early antibiotic use is associated with greater late antibiotic use [ 10 ].…”

“…For example, early and prolonged administration of antibiotics has been associated with an increased risk of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), invasive candidiasis, and death [ 9 , 10 ]. Early antibiotic use is associated with greater late antibiotic use [ 10 ]. Moreover, abnormal development of the intestinal flora during the first weeks of life may increase the risk of adverse long-term outcomes, including diabetes, obesity, asthma, inflammatory bowel disease (IBD), neurodevelopmental disorders, atopic dermatitis, and multiple sclerosis [ 11 ].…”