Antibiotic therapy in neonates and impact on gut microbiota and antibiotic resistance development: a systematic review.

Objectives: To systematically review the impact of antibiotic therapy in the neonatal period on changes in the gut microbiota and/or antibiotic resistance development.

Methods: Data sources were PubMed, Embase, Medline and the Cochrane Database, supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic treatment (yes versus no, long versus short duration and/or broad- versus narrow-spectrum regimens) and subsequent changes in the gut microbiota and/or antibiotic resistance development. We evaluated risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, we used the vote-counting method to perform semi-quantitative meta-analyses. We applied the Grades of Recommendation, Assessment, Development and Evaluation approach to rate the quality of evidence (QoE). Study protocol registration: PROSPERO CRD42015026743.

Results: We included 48 studies, comprising 3 RCTs and 45 observational studies. Prolonged antibiotic treatment was associated with reduced gut microbial diversity in all three studies investigating this outcome (very low QoE). Antibiotic treatment was associated with reduced colonization rates of protective commensal anaerobic bacteria in four of five studies (very low QoE). However, all three categories of antibiotic treatment were associated with an increased risk of antibiotic resistance development, in particular MDR in Gram-negative bacteria, and we graded the QoE for these outcomes as moderate.

Conclusions: We are moderately confident that antibiotic treatment leads to antibiotic resistance development in neonates and it may also induce potentially disease-promoting gut microbiota alterations. Our findings emphasize the need to reduce unnecessary antibiotic treatment in neonates.