Third generation cephalosporins and piperacillin/tazobactam have distinct impacts on the microbiome of critically ill patients

Effective implementation of antibiotic stewardship, especially in critical care, is limited by a lack of direct comparative investigations on how different antibiotics impact the microbiome and antibiotic resistance rates. Here we investigated the impact of two commonly used antibiotics, ceftriaxone (3GC) and piperacillin/tazobactam (TZP) on endotracheal, perineal and faecal microbiomes of intensive care patients in Australia. Patients exposed to either 3GC, TZP, or no beta-lactams (control group) were sampled over time and 16S rRNA amplicon sequencing was performed to examine microbial community diversity and composition. While neither treatment significantly affected diversity, numerous changes to microbiome composition were associated with each treatment. The shifts in microbiome composition associated with 3GC exposure differed from those observed with TZP, consistent with previous reports in animal models. This included a significant increase in Enterobacteriaceae and Enterococcaceae abundance in endotracheal and perineal microbiomes for those administered 3GC compared to the control group. Culture-based analyses did not identify any significant changes in the prevalence of specific pathogenic or antibiotic-resistant bacteria. Exposure to clinical antibiotics has previously been linked to reduced microbiome diversity and increased antimicrobial resistance, but our results indicate that these effects may not be immediately apparent after short-term real-world exposures.