Early initiation of antibiotic therapy and short-term outcomes in preterm infants: a single-centre retrospective cohort analysis

Abstract

Background: Sepsis is one of the most important complications in preterm infants. For this reason, many such infants receive antibiotics during their hospital stay. However, early antibiotic therapy has also been associated with adverse outcome. It is yet largely unclear if the time of onset of antibiotic therapy influences the outcome. We here investigated whether the timing of initiation of antibiotic therapy plays a role in the association between antibiotic exposure and short-term outcome.

Methods: Retrospective analysis of data from 1762 very low birthweight infants born in a German neonatal intensive care unit (NICU) between January 2004 and December 2021.

Results: Antibiotics were administered to 1214 of the 1762 (68.9%) infants. In 973 (55.2%) of the 1762 of infants, antibiotic therapy was initiated within the first two postnatal days. Only 548 (31.1%) infants did not have any antibiotic prescription during their stay in the NICU. Antibiotic exposure at every timepoint was associated with an increased risk of all short-term outcomes analysed in univariable analyses. In multivariable analyses, initiation of antibiotic therapy within the first two postnatal days and initiation between postnatal days 3 and 6 was independently associated with an increased risk of developing bronchopulmonary dysplasia (BPD) (OR 3.1 and 2.8), while later initiation of antibiotic therapy was not.

Conclusion: Very early initiation of antibiotic therapy was associated with an increased risk of BPD. Due to the study design, no conclusions on causality can be drawn. If confirmed, our data suggest that an improved identification of infants at low risk of early-onset sepsis is needed to reduce antibiotic exposure.

Keywords: Epidemiology; Infectious Disease Medicine; Intensive Care Units, Neonatal; Neonatology; Sepsis.

Figure 1

Flowchart showing patients included in the retrospective analysis. A total of 1819 infants met the inclusion criteria (inborn, birth weight below 1500 g). Fifty-seven infants were excluded from the analysis as they died within the first 3 days of postnatal life. ABT, antibiotic therapy.

Figure 2

Infants exposed to antibiotics in dependency of the postnatal day and antibiotics prescribed in the study cohort. Bar graphs showing (A) percentages of antibiotic-exposed preterm infants in dependency of the postnatal day and (B) proportion of different antibiotic preparations in all antibiotic prescriptions as a percentage of prescribed antibiotic doses.