[Seminar] Acquired resistance to polymyxins in Gram negatives; mechanisms, epidemiology, and detection tools

Title: Acquired resistance to polymyxins in Gram negatives; mechanisms, epidemiology, and detection tools
 

Speaker: Laurent Poirel

Affiliation

Chair of Microbiology, Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland

Co-Director INSERM European Laboratory, French National Institute for Health and Medical Research, Paris, France

Co-Director National Reference Center for Emerging Antibiotic Resistance (Switzerland), University of Fribourg,  Fribourg, Swizerland

Abstract

Transferable polymyxin resistance in gram-negative rods has recently been reported from both human and animal enterobacterial isolates. Colistin is an old drug that was first introduced in 1959 but remained on the shelf in human medicine for many years due to renal and neurotoxicity. However, it has been and is still being extensively used in veterinary medicine. We are experiencing a renewed interest for that drug due to the rapid emergence of multidrug-resistant gram negatives in human medicine.

The plasmid-borne mcr genes encode phosphoethanolamine transferases that mediate addition of phosphoethanolamine to the lipid A moiety of the lipopolysaccharide, consequently conferring resistance to polymyxins. Those genes are mainly identified in Escherichia coli, and to a lesser extent in Klebsiella spp. and Salmonella spp.

They have been identified among human E. coli isolates in many different countries, in all continents. They have also been identified in food-producing animals, as well as in vegetables and the environment. High rates of MCR-1-producing E. coli isolates have been identified from pigs in Portugal for instance.

Taken together, this information indicate that (i) the spread of mcr-1 is not recent, it has already occurred worldwide at least due to its location on conjugative plasmids, and (ii) E. coli is so far the main reservoir of this resistance trait either among human, animal, or environmental isolates. This is a source of concern since E. coli isolates are easily exchanged from the environment to humans in which it may stay in a commensal state in the gut flora ; also, it is the number one pathogen for humans.

The heavy usage of colistin in veterinary medicine is therefore of concern. Colistin and polymyxin B are used for treating infections caused by Enterobacteriaceae in rabbits, broilers, veal, beef cattle, dairy cattle, and mostly in pigs in Europe.

The occurrence of polymyxin resistance in animal isolates has been very likely underestimated and unrecognized for years, since determination of polymyxin susceptibility is difficult. We have recently developed rapid diagnostic techniques in order to facilitate the detection of acquired colistin resistance. Also, screening media have been developed in order to implement screening and surveillance studies, with the ultimate goal to control the spread of those threatening resistance determinants.

Laurent Poirel (Fribourg, Switzerland)

Dr Laurent Poirel is Associate Professor at the Medical and Molecular Microbiology Unit, Dept of Medicine, University of Fribourg, Switzerland. He is co-director of the Swiss National Reference Center on Emerging Resistance to Antibiotics. His research interests are emerging mechanisms of resistance to ß-lactams, polymyxins, and quinolones in Gram-negative rods, both in human and in veterinary medicine. He is specialized on the genetics of acquisition of resistance genes in Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii, plasmid-mediated quinolone resistance, and polymyxin resistance determinants in Enterobacteriaceae. He has co-invented a series of rapid diagnostic tests for detection of emerging resistance traits, including the Carba NP test. In addition, he is co-inventor of a series of 12 patents mainly corresponding to rapid diagnostic tests or antibiotic selective media. He is the author of 500 publications in international journals, and Associate Editor of two highly-ranked journals, i.e. Antimicrobial Agents and Chemotherapy and Journal of Antimicrobial Agents.