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Swedish researchers warn of over-use of antibiotics with newborns

Low exposure to antibiotics in newborns treated in neonatal units over a nine-year period was not associated with an increased risk of early-onset sepsis (EOS), found Swedish researchers, but they warned of higher-than-recommended antibiotic use for these infants.

They said there was a low prevalence of EOS and low mortality associated with the condition, and called for a reduction in unnecessary antibiotic use.

Low EOS incidence

Using data from the Swedish National Quality Register and the Swedish Medical Birth Register, the scientists, from the Sweden Neonatal Antibiotic Use study, analysed intravenous antibiotic use during the first week of life, the duration of antibiotic therapy, the rates of culture-proven EOS, and mortality associated with EOS in all late-preterm and full-term babies born from 2012 to 2020 in all neonatal units.

CIDRAP reports that all hospital live births from 34 weeks’ gestation were included, the aim being to assess how much antibiotic use for EOS in newborns is actually warranted.

While neonatal sepsis is a serious condition that can become life-threatening if these infants don’t receive prompt antibiotic treatment, the authors said the fear of missing EOS, which can be caused by bacteria transmitted from the mother to the baby during birth, is one of the contributors to overuse of antibiotics in neonatal units.

Several studies have found that this exposure in early life disrupts the microbiome and may be associated with increased risk of several – later – adverse outcomes, including allergies, obesity, diabetes and inflammatory bowel disease.

Of the 1 025 515 babies born at gestational age (GA) 34 weeks or later who were included in the study, 19 286 (1.88%; 39.9% female; median GA, 40 weeks) were treated with antibiotics in the first week. Of those who received antibiotics, 647 (3.4%) had EOS, and nine (1.4%) died.

The incidence of EOS was 0.63 per 1 000 newborns, and the incidence of culture-proven sepsis was 0.70. The most common pathogens found in blood cultures were group B Streptococcus (GBS, 51% of positive blood cultures), Escherichia coli (11%), and Staphylococcus aureus (10%).

Longer than usual dosage

The median duration of antibiotic use in newborns without EOS was five days, and there were 113 antibiotic-days per 1 000 live births. Although there was no significant change in exposure to antibiotics or antibiotic-days per 1 000 live births during the study period, EOS incidence fell from 0.74 per 1 000 newborns in 2012 to 0.34 in 2020.

The authors say the decline in EOS was mainly due to the reduction in the incidence of GBS, which may be linked to intrapartum antibiotic prophylaxis (prevention) guidelines.

For each newborn with EOS, antibiotics were initiated in 29 of them, and 173 antibiotic-days were dispensed.

The authors say that while antibiotic use for each case of EOS was considerably lower than observed in previous studies, it was still too high.

In addition, the median duration of treatment they found (five days) is longer than recommended in international guidelines, which call for discontinuation of antibiotics within 36 to 48 hours if clinical suspicion of EOS has substantially decreased.

“Our results indicate that a relatively low rate of antibiotic use among late-preterm and full-term newborns with maintained low morbidity and mortality is possible in a high-income setting,” they wrote. “Yet, there remains a high burden of treatment compared with the incidence of EOS and mortality.”

Study details

Antibiotic Use in Late Preterm and Full-Term Newborns

Johan Gyllensvärd, Marie Studahl Lars Gustavsson et al.

Published in JAMA Network on 22 March 2024

Abstract

Importance
Antibiotic treatment saves lives in newborns with early-onset sepsis (EOS), but unwarranted antibiotic use is associated with resistant bacteria and adverse outcomes later in life. Surveillance is needed to optimise treatment strategies.

Objective
To describe antibiotic use in association with the incidence and mortality from EOS among late-preterm and full-term newborns.

Design, Setting, and Participants
The Sweden Neonatal Antibiotic Use study was a nationwide observational study that included all late-preterm and full-term neonates born from January 1, 2012, to December 31, 2020, in neonatal units of all levels. All hospital live births from 34 weeks’ gestation during the study period were included in the study. Data were collected from the Swedish Neonatal Quality Register and the Swedish Medical Birth Register. Data were analyzed from August 2022 to May 2023.

Exposure
Admission for neonatal intensive care during the first week of life.

Main Outcomes and Measures
The main outcomes were the usage of intravenous antibiotics during the first week of life, the duration of antibiotic therapy, the rate of culture-proven EOS, and mortality associated with EOS.

Results
A total of 1 025 515 newborns were included in the study; 19 286 neonates (1.88%; 7686 girls [39.9%]; median [IQR] gestational age, 40 [38-41] weeks; median [IQR] birth weight, 3610 [3140-4030] g) received antibiotics during the first week of life, of whom 647 (3.4%) had EOS. The median (IQR) duration of antibiotic treatment in newborns without EOS was 5 (3-7) days, and there were 113 antibiotic-days per 1000 live births. During the study period there was no significant change in the exposure to neonatal antibiotics or antibiotic-days per 1000 live births. The incidence of EOS was 0.63 per 1000 live births, with a significant decrease from 0.74 in 2012 to 0.34 in 2020. Mortality associated with EOS was 1.39% (9 of 647 newborns) and did not change significantly over time. For each newborn with EOS, antibiotic treatment was initiated in 29 newborns and 173 antibiotic-days were dispensed.

Conclusions and Relevance
This large nationwide study found that a relatively low exposure to antibiotics is not associated with an increased risk of EOS or associated mortality. Still, future efforts to reduce unwarranted neonatal antibiotic use are needed.

 

JAMA Network article – Antibiotic Use in Late Preterm and Full-Term Newborns (Open access)

 

CIDRAP article – Study highlights potential to reduce antibiotic use in newborns (Open access)

 

See more from MedicalBrief archives:

 

New antibiotics vital to stem newborn deaths

 

SA and Kenya in global trial for neonatal sepsis treatment

 

Probiotic mixture reduces sepsis by 40% in infants

 

 

 

 

 

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