Editor’s Note: Prof. Etienne Ruppé, a professor of bacteriology at the Université Paris Cité and researcher at the IAME unit, is conducting a study on the impact of β-lactam antibiotics on the gut microbiota. His research primarily focuses on ceftriaxone, piperacillin-tazobactam, and ceftazidime-avibactam, uncovering significant findings regarding the differential impacts and lasting effects of these antibiotics on gut microbial communities. We interviewed Prof. Ruppé to discuss his research findings and their potential implications for antibiotic therapy and microbial health.
Infectious Disease Frontier: In your study, you compared the effects of three β-lactam antibiotics—ceftriaxone, piperacillin-tazobactam, and ceftazidime-avibactam—on the gut microbiota. You found that ceftazidime-avibactam had the most significant impact. Could you please elaborate on the reasons for this difference?
Prof. Ruppé: It’s crucial for us to understand which antibiotic most significantly affects the microbiota. By using a very specific clinical trial to compare the effects of these three beta-lactam regimens, we observed that ceftazidime-avibactam had a greater impact than the others. This could be due to the high concentrations of ceftazidime-avibactam in the gut, which may overcome bacterial resistance, or due to the high sensitivity of anaerobic bacteria in the gut to this antibiotic. It proved more effective than piperacillin-tazobactam, although we might have underestimated the effect of piperacillin-tazobactam due to some unsequenced samples, where the impact might have been so strong that no DNA was left.
Infectious Disease Frontier: Your research revealed that the impact of ceftazidime-avibactam on the gut microbiota persisted even 30 days after the cessation of treatment. What are the clinical implications of this long-term effect?
Prof. Ruppé: Currently, we don’t fully understand the long-term effects. We’re still evaluating the impacts, needing to define what loss of diversity and richness mean in clinical terms. It’s uncertain whether the recovery time, whether 45 days or 15 days, significantly alters clinical outcomes. However, since the impact of ceftazidime-avibactam is notably greater, using it may warrant caution due to potential clinical consequences associated with delayed recovery.
Infectious Disease Frontier: Additionally, your study observed the selective expression of β-lactamase genes. How do these changes in gene abundance contribute to the development of antibiotic resistance? And what areas of research do you believe should be prioritized in the future to address this issue?
Prof. Ruppé: This observation is really one of the first stones on the pathway of research that we are pursuing understanding the mechanisms of defence of the gut microbiota against antibiotics. All observations demonstrated that the more beta-lactamase you have in the gut, the more you are protected against antibiotic impacts on the gut. So we try to decipher these mechanisms, and first we have to identify the beta-lactamases in the gut. This is really challenging because they differ from the beta-lactamase we know, and we have to characterize them by their resistance phenotype. And from that, we will try to understand which beta-lactamases are protective from the action of antibiotics. this is just the beginning of deciphering an old concept.
