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

Abstract

BackgroundSepsis 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.MethodsRetrospective analysis of data from 1762 very low birthweight infants born in a German neonatal intensive care unit (NICU) between January 2004 and December 2021.ResultsAntibiotics 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.ConclusionVery 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.

Sustaining the Continued Effectiveness of an Antimicrobial Stewardship Program in Preterm Infants

“…Approximately 14% of late preterm and full-term neonates and up to 90% of extremely-low-birth-weight (ELBW) infants receive empirical antibiotics immediately after birth, although culture-proven EOS occurs in only a few of these neonates [ 8 ]. Antibiotic exposure during the first few days of life may have important adverse effects [ 9 , 10 ]. Indeed, early and prolonged exposure to antibiotics may increase the risk of antimicrobial resistance and lead to dysbiosis, with a potential negative impact, especially in preterm infants [ 8 , 9 , 10 ].…”

“…Antibiotic exposure during the first few days of life may have important adverse effects [ 9 , 10 ]. Indeed, early and prolonged exposure to antibiotics may increase the risk of antimicrobial resistance and lead to dysbiosis, with a potential negative impact, especially in preterm infants [ 8 , 9 , 10 ]. Short- and long-term morbidity after antibiotic exposure has been reported in uninfected preterm infants [ 8 , 9 , 10 ].…”

“…Indeed, early and prolonged exposure to antibiotics may increase the risk of antimicrobial resistance and lead to dysbiosis, with a potential negative impact, especially in preterm infants [ 8 , 9 , 10 ]. Short- and long-term morbidity after antibiotic exposure has been reported in uninfected preterm infants [ 8 , 9 , 10 ]. For example, early and prolonged administration of antibiotics has been associated with an increased risk of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), invasive candidiasis, and death [ 9 , 10 ].…”

“…Short- and long-term morbidity after antibiotic exposure has been reported in uninfected preterm infants [ 8 , 9 , 10 ]. For example, early and prolonged administration of antibiotics has been associated with an increased risk of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), retinopathy of prematurity (ROP), invasive candidiasis, and death [ 9 , 10 ]. Early antibiotic use is associated with greater late antibiotic use [ 10 ].…”

“…Moreover, abnormal development of the intestinal flora during the first weeks of life may increase the risk of adverse long-term outcomes, including diabetes, obesity, asthma, inflammatory bowel disease (IBD), neurodevelopmental disorders, atopic dermatitis, and multiple sclerosis [ 11 ]. Prolonged and repeated antibiotic courses in uninfected infants accelerate the development and spread of antimicrobial resistance (AMR) and increase the risk of morbidity and mortality due to multidrug-resistant organisms (MDROs), as empiric therapy is less likely to be effective against these pathogens [ 9 , 10 , 12 ]. Infections caused by MDROs are also associated with prolonged hospitalization, increased costs, and death [ 12 ].…”