Effects of Antibiotic Treatment with Piperacillin/Tazobactam versus Ceftriaxone on the Composition of the Murine Gut Microbiota

Abstract

ABSTRACT Effective antimicrobial stewardship requires a better understanding of the impact of different antibiotics on the gut microflora. Studies with humans are confounded by large interindividual variability and difficulty in identifying control cohorts. However, controlled murine models can provide valuable information. In this study, we examined the impact of a penicillin-like antibiotic (piperacillin-tazobactam [TZP]) or a third-generation cephalosporin (ceftriaxone [CRO]) on the murine gut microbiota by analysis of changes in fecal microbiome composition by 16S rRNA amplicon sequencing and standard microbiology. Resistance to colonization by multidrug-resistant Escherichia coli sequence type 131 (ST131) and Klebsiella pneumoniae ST258 was also tested. Changes in microbiome composition and a significant (P < 0.05) decrease in diversity occurred in all treated mice, but dysbiosis was more marked and prolonged after CRO exposure, with a persistent rise in Proteobacteria. Enterobacteriaceae blooms occurred in all antibiotic-treated mice, but for TZP, unlike CRO, these were significant only under direct antibiotic pressure. At the height of dysbiosis after antibiotic termination, the murine gut was highly susceptible to colonization with both multidrug-resistant enterobacterial pathogens. Cohabitation of treated mice with untreated individuals had a notable mitigating effect on dysbiosis of treated guts. The administration of a third-generation cephalosporin caused a more severe imbalance in the murine fecal microflora than that caused by a penicillin/β-lactam inhibitor combination with comparable activity against medically important virulent bacteria. At the height of dysbiosis, both antibiotic treatments equally led to microbial instability associated with loss of resistance to gut colonization by antibiotic-resistant pathogens.