Effects of early postpartum antibiotic exposure on the incidence of early-onset sepsis

In a recently published study Jama Network OpenResearchers investigated the effects of early postnatal antibiotic exposure among infants in participant networks of high-income countries. They also measured the incidence of early-onset sepsis (EOS) and death in all infants born between January 1, 2014, and December 31, 2018, whose gestational age was 34 weeks or greater.

Background

Antibiotics are often prescribed in neonatal units, and their prompt initiation saves lives in cases of neonatal EOS. However, what drives the overuse of antibiotics early in life is the lack of precision of the diagnostic tools used to detect sepsis.

The incidence of EOS among late preterm and term newborns has decreased over the past few years. That’s why the World Health Organization (WHO) launched antimicrobial management (AMS) programs to help doctors optimize antibiotic prescriptions and improve patient outcomes.

Neonatal antibiotic exposure disrupts the developing microbiome and causes several later diseases, including asthma, diabetes, allergies, and inflammatory bowel disease. In addition, these treatments negatively affect the length of hospital stay and breastfeeding rates and increase health care costs. Overall, AMS is very important in early life.

about the study

In the current retrospective, cross-sectional study, researchers analyzed early postnatal antibiotic exposure, the incidence of culture-proven EOS, and all-cause and EOS-related death among infants in both late preterm and full-term infants. These infants received intravenous antibiotics for varying times in the first week after birth.

Researchers defined EOS as culture-proven EOS with a positive blood or cerebrospinal fluid (CSF) culture in the first postnatal week. diphtheroids or micrococci species as pollutants. Similarly, proven infections are cultures that show growth of coagulase-negative staphylococci (CoNS) for more than five days. Newborns without EOS were given antibiotics but were not diagnosed with EOS. The team obtained indications for antibiotic therapy from electronic health records and records of infants.

Regarding mortality, the team defined neonatal death as death before discharge or within 28 days among hospitalized cases. EOS-related mortality was death within 28 days of positive blood or CSF culture. They calculated the proportion of newborns treated with antibiotics by dividing the number of newborns who received at least one dose of antibiotics in the first postnatal week by live births. The duration of antibiotic therapy was calendar days with at least one dose of antibiotics. The sum of antibiotic days for each newborn divided by live births was antibiotic days per 1000 live births, indicating antibiotic exposure.

The team reported all EOS episodes except CoNS. They defined its incidence as the rate in all live-born neonates. All-cause mortality was deaths among all live-born neonates independent of antibiotic therapy and EOS. Finally, the team calculated odds ratios (ORs) using the Mantel-Haenszel method for stratification. They analyzed data from October 2021 to March 2022 separately for all workgroups and networks.

Study findings

Of the 757,979 newborns born in 13 networks from 11 countries, 2.86%, 59.4% were male, 59.4%, with a median gestational age of 39 weeks and a median birth weight of 3250 grams, received intravenous antibiotics in the first postnatal week. The proportion of neonates receiving antibiotics between nets ranged from 1.18% to 12.45% (mean 3%), resulting in 135 days of antibiotic exposure per 1000 live births. The incidence of EOS was 0.49 cases per 1000 live births and the mortality rate associated with EOS was 3.20%. The median duration of treatment was nine days for neonates with EOS and four days for those without EOS. For each case of EOS, 58 newborns were given antibiotics, and the team gave antibiotics for 273 days.

solution

Compared with the EOS (disease) burden, early postnatal antibiotic use (treatment) was high and disproportionate among participating infants. In addition, the researchers noted up to nine-fold wide variations in the use of antibiotics in preterm postpartum across these international networks. Because the treatment burden is more important than the disease burden, a neonatal antibiotic cure rate of 1% or less can be achieved.

More importantly, the current study has identified a set of indicators informing dimensions that will facilitate benchmarking and future interventions to safely reduce antibiotic exposure in neonates. It may help reduce the risk of antimicrobial resistance and protect the thriving microbiome to improve long-term health.