Fecal and oropharyngeal microbiota from infants with cystic fibrosis on and off beta-lactam antibiotics.

Cystic fibrosis (CF) is a multiorgan disease caused by mutations in the CF transmembrane conductance regulator (CFTR) that alter the transport of fluid and ions across cell membranes. Complications from CF, including lung infections, begin in early in life, and infants with cystic fibrosis frequently receive systemic antibiotics for respiratory symptoms. Systemic antibiotic treatments can impact all colonizing and infecting microbes inhabiting patients, regardless of the intended target organism(s). We studied the simultaneous effects on the respiratory and fecal microbiomes of beta-lactam antibiotics administered for respiratory symptoms in infants with CF to compare the magnitude and duration of intended (respiratory) and unintended (fecal) antimicrobial action. We performed shotgun metagenomic sequencing and qPCR analysis of oropharyngeal (OP) and fecal samples from 14 infants with CF off and on beta-lactam therapy, and from 5 untreated control infants with CF. We found that beta-lactam antibiotic treatments for CF respiratory exacerbations were followed by a longer-lasting change in fecal than OP microbiota. These changes led to alterations in known antibiotic resistance gene complements in both sample types that could not be explained by selection for canonical beta-lactam resistance genes, limiting the ability to predict off-target effects with pre-treatment testing and potentially impacting the effects of subsequent antibiotic treatments.