Fighting antimicrobial resistance in infants

There is an urgent need for new strategies to combat antimicrobial resistance. Vulnerable groups, in particular preterm and term infants, are highly exposed to antibiotic interventions during early life, and often for extended periods. While antibiotics have saved millions of lives, the worldwide rise in antibiotic resistance leaves sad imprints in this group, with thousands suffering or dying during the first days of life due to resistance to antibiotics. In addition to resistance during this critical period of development, antibiotics promote microbiome disruptions that can have life-long consequences, including among other conditions, increased risk to respiratory infections. In this project, we aim to gain insights into how the microbiome and the collection of resistance genes carried by the microbiome, the resistome, develop in infants in response to different antibiotic interventions. Using mouse models of respiratory infection and sepsis, we will investigate how different antibiotic therapies currently used in preterm/term infant care affect the microbiome composition, resistance profile and immune responses, and if such effects may predispose the host to infections with the bacterial pathogen Streptococcus pneumoniae. Finally, probiotics, live microorganisms intended to provide health benefits when consumed, will be assessed for its potential to lower resistance development in vivo, and prevent antibiotic-induced deleterious effects on microbiome development. Of note, it is unavoidable to replace mouse model for this host-microbiome interaction study. We have reduced the number of animals, but also use sufficient numbers (1316 mice) to provide reliable findings. We expect that although the mice undergoing experimentation may show short-term mild to moderate distress, they will not show any significant impairment of their well-being or general condition. We have enough experience working with various mouse models, including pneumococcal infection models, as evident from our current projects having FOTS ID: 8481 and 10515. Overall, the results are expected to (1) provide increased knowledge on human microbiome and resistance development, (2) develop new strategies to fight antibiotic resistance and (3) provide information to better guide antibiotic use in infants.