Antibiotics and microbiota colonization in infancy: What lessons can we learn?

This thesis is divided into 3 parts. In the first part, the effect of perinatal antibiotic use on the microbiome and on necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) is described. Maternal antibiotic use during birth leads to microbiome disturbances in children born vaginally, as described in a systematic review. Maternal antibiotic use during caesarean section did not seem to have an effect on the child's microbiome in a randomized controlled trial. Postpartum antibiotic use did appear to influence the risk of NEC and LOS in a large observational cohort of very pretem infants. In the second part, it was investigated in an observational cohort whether a molecular test (IS-pro) and new biomarker (presepsin) could diagnose early-onset sepsis directly postpartum. In preterm infants, presepsin had a high accuracy. Implementation of presepsin may lead to a decrease in unnecessary antibiotic use in uninfected infants. Most IS-pro results were comparable to the conventional culture results, the current gold standard. Future research is needed to validate these tests. In the third part, the potential protective effects of probiotics on antibiotic-associated diarrhoea (AAD) and on antibiotic induced microbial aberrations was studied in a randomized trial. The use of probiotics resulted in a lower incidence of AAD. Probiotics also had a small effect on the microbiome. Future research is needed to validate whether probiotics have protective effects on the microbiome and whether their use should be incorporated in clinical guidelines

Antibiotics and microbiota colonization in infancy: What lessons can we learn?

This thesis is divided into 3 parts. In the first part, the effect of perinatal antibiotic use on the microbiome and on necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) is described. Maternal antibiotic use during birth leads to microbiome disturbances in children born vaginally, as described in a systematic review. Maternal antibiotic use during caesarean section did no

Antibiotics and microbiota colonization in infancy: What lessons can we learn?

This thesis is divided into 3 parts. In the first part, the effect of perinatal antibiotic use on the microbiome and on necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) is described. Maternal antibiotic use during birth leads to microbiome disturbances in children born vaginally, as described in a systematic review. Maternal antibiotic use during caesarean section did not seem to have an effect on the child's microbiome in a randomized controlled trial. Postpartum antibiotic use did appear to influence the risk of NEC and LOS in a large observational cohort of very pretem infants. In the second part, it was investigated in an observational cohort whether a molecular test (IS-pro) and new biomarker (presepsin) could diagnose early-onset sepsis directly postpartum. In preterm infants, presepsin had a high accuracy. Implementation of presepsin may lead to a decrease in unnecessary antibiotic use in uninfected infants. Most IS-pro results were comparable to the conventional culture results, the current gold standard. Future research is needed to validate these tests. In the third part, the potential protective effects of probiotics on antibiotic-associated diarrhoea (AAD) and on antibiotic induced microbial aberrations was studied in a randomized trial. The use of probiotics resulted in a lower incidence of AAD. Probiotics also had a small effect on the microbiome. Future research is needed to validate whether probiotics have protective effects on the microbiome and whether their use should be incorporated in clinical guidelines

Association between duration of early empiric antibiotics and necrotizing enterocolitis and late-onset sepsis in preterm infants: a multicenter cohort study

The threshold to initiate empiric antibiotics for suspicion of early-onset sepsis (EOS) is low in preterm infants. Antibiotics' effects on short-term outcomes have recently been debated. We aimed at exploring the extent of early empiric antibiotic exposure (EEAE) in preterm infants and the association between the duration of EEAE with necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) within different EEAE groups. EEAE practice for suspicion of EOS was evaluated in all included infants (gestational age  72 h). Infants with EEAE ≤ 72 h had a lower incidence of NEC compared to both infants without EEAE (adjusted odds ratio (aOR) 0.39; 95% confidence interval (CI) [0.19-0.80]; p = 0.01) and with prolonged EEAE (> 72 h) (aOR [95%CI]: 0.58 [0.35-0.96]; p = 0.03). With every additional day of EEAE, LOS incidence decreased (aOR [95%CI]: 0.90 [0.85-0.97]; p = 0.003). CONCLUSION: Almost 90% of preterm infants who have negative blood culture results in the first 72 h of life are exposed to EEAE under suspicion of EOS. One-fourth has prolonged EEAE. Duration of EEAE was differently associated with NEC and LOS incidence. The effects of antibiotics, and potentially induced microbial dysbiosis related to development of NEC and LOS, should further be explored. WHAT IS KNOWN: • Preterm infants often receive antibiotics empirically directly after birth for suspicion of early-onset sepsis. • The effects of the duration of early empirical antibiotic exposure on the risk for necrotizing enterocolitis and late-onset sepsis are debated. WHAT IS NEW: • Almost 90% of preterm infants with a gestational age below 30 weeks are exposed to antibiotics empirically after birth despite negative culture results. In a quarter of these culture-negative infants, empirical antibiotics are prolonged. • A short course of empirical antibiotics (≤72h) is associated with decreased odds for necrotizing enterocolitis compared to both prolonged (>72h) or no empirical antibiotics after birth. Furthermore, every additional day of empirical antibiotic exposure is associated with decreased risk for late-onset sepsis in the first month of life