Early antibiotics in noncritical premature infants without clear infection linked to adverse outcomes

1. In a prospective cohort study, early antibiotic use in preterm, non-critical infants without a clear bacterial infection was associated with an increased risk of developing bronchopulmonary dysplasia (BPD), and increased late antibiotic use.

2. Longer duration of early antibiotics and the use of broad-spectrum antibiotics each amplified the risk of developing BPD.

Evidence Rating Level: 2 (Good)

Study Rundown: Though early antibiotic use is common in preterm infants, the risks and benefits of prescribing antibiotics to infants without a clear bacterial infection have not been well-studied. This prospective cohort study of over 21,000 infants (mean gestational age 31 weeks) from 25 NICUs across China aimed to determine outcomes associated with early intravenous antibiotic use (within the first 7 days of life) in non-critical infants without an infection-related morbidity. 18,302 infants were given early antibiotics, while 3,238 infants did not receive early antibiotics. Following the generation of two analytic models to minimize confounders, early antibiotic use was independently associated with an increased risk of developing bronchopulmonary dysplasia (BPD) and late antibiotic use. The risk of developing BPD was further increased when broad-spectrum antibiotics or prolonged courses of early antibiotics were used. Furthermore, early antibiotic use was not associated with decreased mortality, although narrow-spectrum and prolonged early antibiotic use were associated with a decreased risk of necrotizing enterocolitis (NEC). This study has several important limitations. Its generalizability is limited by the fact that all included hospitals were located in China, where endemic pathogens, prescribing practices (e.g., aminoglycosides are not routinely used), and breastfeeding rates may differ from other countries. The average gestational age of included infants was 31 weeks, and the study’s findings may not be applicable to more premature infants. Finally, while authors attempted to control for some markers of illness severity, residual confounding that could account for earlier antibiotic administration in more ill infants may have been present. Overall, this study suggests that the early use of antibiotics (especially prolonged courses of broad-spectrum antibiotics) may be associated with an increased risk of developing BPD and late antibiotic use in preterm infants who are noncritically ill and have no clear infection.

Click to read the study in Pediatrics

Relevant Reading: Reducing Early Antibiotic Use: A Quality Improvement Initiative in a Level III Neonatal Intensive Care Unit

In-Depth [prospective cohort]: 21,540 preterm infants born at less than 34 weeks’ gestation from 25 level III NICUs across 19 provinces in China were included in the study. 18,302 (85.0%) received early antibiotics. Early antibiotic use was defined as use of intravenous (IV) antibiotics within the first 7 days after birth, while late antibiotic use was defined as use of IV antibiotics after the first 7 days of birth. Those with infectious-related morbidities (culture-proven or clinical sepsis, ventilator-associated pneumonia, urinary tract infection, NEC, spontaneous intestinal perforation, and any surgery) were excluded. Two statistical models were generated to account for potential confounding variables. Early antibiotic use was associated with an increased risk of BPD (aOR, 1.28; 95% CI 1.05-1.56) and 4.64 times greater odds of late antibiotic use (95% CI 4.19-5.14) compared to infants who did not receive early antibiotics. 11474 (53.3%) of infants received broad-spectrum antibiotics, and 6828 (37.1%) received narrow-spectrum antibiotics. Infants receiving broad-spectrum antibiotics had 1.50 times higher odds of developing BPD (95% CI 1.23-1.84) and 6.5 times higher odds (95% CI 5.86-7.31) of receiving late antibiotic treatment compared to infants who did not receive early antibiotics. Infants who received narrow-spectrum antibiotics had 3.07 times higher odds (95% CI 2.75-3.44) of receiving late antibiotic treatment.

Image: PD

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