Ceftriaxone and cefotaxime have similar effects on the intestinal microbiota in human volunteers treated by standard doses regimens

Background Ceftriaxone has a higher biliary elimination than cefotaxime (40% vs 10%), which may result in a more pronounced impact on the intestinal microbiota. Methods We performed a monocenter, randomized open-labelled clinical trial in 22 healthy volunteers treated by intravenous ceftriaxone (1g/24hrs) or cefotaxime (1g/8hrs) for 3 days (ClinicalTrials.gov NCT02659033). We collected fecal samples for phenotypic analyses, 16S rRNA gene profiling and measurement of antibiotic concentration, and compared between groups the evolution of microbial counts and indices of bacterial diversity over time. Plasma samples were drawn at day 3 for pharmacokinetic analysis. Results Emergence of 3rd generation cephalosporin resistant Gram-negative enteric bacilli (Enterobacterales), Enterococcus spp., or noncommensal microorganisms were not significantly different between groups. Both antibiotics reduced the counts of total Gram-negative enteric bacilli and decreased bacterial diversity, without significant difference between groups. All but one volunteer from each group exhibited undetectable levels of antibiotic in feces. Plasma pharmacokinetic endpoints were not correlated to alteration of bacterial diversity of the gut. Conclusions Both antibiotics markedly impact the intestinal microbiota, without any significant difference when standard clinical doses were administered for 3 days. This might be related to similar daily amounts of antibiotics excreted through the bile using a clinical regimen.