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.
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.
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.
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.
Comments
To the editor re. "Reduction of Infection in Neonatal Intensive Care Units Using the Evidence-based Practice for Improving Quality (REIN-EPIQ) Study Group"
In SIBEN, the Iberoamerican Society of Neonatology (www.siben.net) we have been very interested in this topic, believing that “a rational use of antibiotics implies that patients receive those adequate for their clinical needs, in correct doses according to their individual conditions, during an adequate period of time, and at the lowest cost for them and their community”[2]. After reviewing the literature related to the use of ATB in perinatal medicine up to February 2020, we concluded that “ATB abuse in perinatal medicine ranged from 50% to 70%, with even higher rates in some neonatal centers. Adverse effects include death, increased microbial resistance, along with microbiome abnormalities and dysbiosis that lead to serious life-long complications such as infections, allergies, autoimmune disorders, gastrointestinal disorders, arthritis, asthma, obesity, and perhaps cancer”. We concluded that the need to optimize the use of ATB in perinatal medicine has never been more urgent, as we calculated that “only 4 NICUs, with 1000 admissions per year, savings were estimated at US$230,000 per year”. We later published similar conclusions, suggesting that the perinatal period is characterized by an excessive use of antibiotics [3]. A European study looking at variations in antibiotic use concluded also that “the management of neonatal sepsis in European NICUs is diverse, with a high self-reported adherence to the local clinical guidelines, ands homogeneity in the combination of antibiotics in EOS but less in LOS [4]. We had previously reviewed this in our 10th Clinical Consensus on Suspected Neonatal Sepsis [5].
The time to act is now!
References:
[1]Yu W, Zhang L, Li S, Yan W, Bai R, Yang Z, Shi J, Yuan J, Yang C, Cai W, Wang Y, Zhang Y, Gu X, Cao X, Huang Y, Hong L, Zhou Q, Yang Y, Lee SK, Jiang S, Cao Y; Reduction of Infection in Neonatal Intensive Care Units Using the Evidence-based Practice for Improving Quality (REIN-EPIQ) Study Group. Early Antibiotic Use and Neonatal Outcomes Among Preterm Infants Without Infections. Pediatrics. 2023 May 1;151(5):e2022059427. doi: 10.1542/peds.2022-059427. PMID: 37042203
[2]Cardetti M, Rodríguez S, Sola A. Uso (y abuso) de antibióticos en la medicina perinatal [Use (and abuse) of antibiotics in perinatal medicine]. An Pediatr (Engl Ed). 2020 Sep;93(3):207.e1-207.e7. Spanish. doi: 10.1016/j.anpedi.2020.06.010. Epub 2020 Jul 15. PMID: 32680672.
[3]Sola A. Abuse of Antibiotics in Perinatology: Negative Impact for Health and the Economy. NeoReviews. 2020 Aug;21(8):e559-e570. doi: 10.1542/neo.21-8-e559. PMID: 32737173.
[4]Garrido F, Allegaert K, Arribas C, Villamor E, Raffaeli G, Paniagua M, Cavallaro G, On Behalf Of European Antibiotics Study Group Easg. Variations in Antibiotic Use and Sepsis Management in Neonatal Intensive Care Units: A European Survey. Antibiotics (Basel). 2021 Aug 27;10(9):1046. doi: 10.3390/antibiotics10091046. PMID: 34572631; PMCID: PMC8469483.
[5]Sola A, Mir R, Lemus-Varela L, Fariña D, Ortiz J, Golombek SG, y miembros del X Consenso Clínico SIBEN: Sospecha de sepsis neonatal: X Consenso Clínico de la Sociedad Iberoamericana de Neonatología. [Suspected Neonatal Sepsis:10th Clinical Consensus of the Iberoamerican Society of Neonatology]. NeoReviews 2020 Aug; 21 (8) e505-e534; DOI: https://doi.org/10.1542/neo.21-8-e505