UMR Inserm 1092

About this entry

Main research field of the team is the molecular basis of antimicrobial resistance. We develop fundamental research projects on the mechanisms of antibacterial drug resistance but also translational projects from bench to bedside. The correlation between antibiotic use and the emergence of bacterial resistance is clear and many countries have developed strategies to prevent antibiotic overuse. The concept of personalized medicine will require the development of rapid diagnostic tests (RDT) to enable clinicians to choose the right antibiotic for the right micro-organism and the right patient.

Antibiotic resistance among Gram-negative bacteria (GNB) can be mediated by hundreds different genes. Along with transposons and plasmids, integrons are important genetic substrates for resistance genes. Integrons are genetic elements that play a major role in multidrug resistance in GNB through their ability to capture and express antibiotic resistance genes. Several studies have shown a link between antibiotic resistance and the presence of integrons in GNB . We therefore suspected that integrons might represent a global marker of acquired resistance. We so develop translational research programs to evaluate the role of integrons as biomarkers of antibiotic resistance acquisition in the clinical setting. Thanks to a qPCR we developed, we first decided to detect integrons from positive blood cultures with GNB. Negative predictive values (NPVs) were >90% for resistance to third-generation cephalosporins, aminoglycosides, ciprofloxacin and cotrimoxazole. In the global objective of preserving broad-spectrum antibiotics, this NPV could be a very useful information for clinicians.

The idea now is to launch a multicentric clinical research program to evaluate the clinical impact of the integron response on patient management. We will focus on  septic patients with urinary tract infections at risk of multidrug resistance.

Integrons are global markers of multidrug resistance among Gram-negative bacteria. Idea is to develop a commercial test so as to detect them directly from biological samples like urines for which GNB prevalence is high or from blood cultures positive with GNB. In a previous study on blood cultures we published (Barraud et al, 2014, IJAA), negative predictive values (NPVs) of integrons were >90% for resistance to third-generation cephalosporins, aminoglycosides, ciprofloxacin and trimethoprim/sulfamethoxazole. In the current context of antibiotic stewardship, these good NPVs indicate that this method might be useful for preserving broad-Spectrum antibiotics. We are currently running a study wher integrons are directly detected from urines of septic patients with urosepsis. Preliminary results indicate also high NPV values. Next step will be to launch a clinical research study with result of the integron qPCR given to the clinician in "real-time". 

If you would like to be introduced to this team for collaboration, get in touch with the Longitude prize.