Vancomycin resistance: occurrence, mechanisms and strategies to combat it.
Vancomycin has long been considered the antibiotic of last resort against serious and multi-drug-resistant infections caused by Gram-positive bacteria. However, vancomycin resistance has emerged, first in enterococci and, more recently, in Staphylococcus aureus. Here, the authors attempt to review the prevalence and the mechanisms of such resistance. Furthermore, they focus on strategies that have been developed or are under current investigation to overcome infections caused by vancomycin-resistant strains. Among these are glycopeptide derivatives with higher potency than vancomycin, small molecules that resensitise bacteria to the antibiotic and novel non-glycopeptide antibiotics. These agents are targeted to interfere with protein and/or peptidoglycan (PG) synthesis and integrity or with membrane permeability. Whilst most of these agents are still in clinical or preclinical development, some have entered the clinic and currently represent the only option for treating vancomycin-resistant enterococci (VRE).
Boneca
Ivo G
IG
Unité de Pathogénie Bactérienne des Muqueuses, Institut Pasteur, 25 - 28 Rue du Docteur Roux, 75724 Paris cedex 15, France. bonecai@pasteur.fr
Chiosis
Gabriela
G
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000145:classification / Q000494:pharmacology; D001426:Bacterial Proteins / Q000502:physiology; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial; D016983:Enterococcus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008954:Models, Biological; D010457:Peptidoglycan / Q000378:metabolism; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014640:Vancomycin / Q000494:pharmacology; D020713:Vancomycin Resistance / Q000187:drug effects / Q000235:genetics / Q000502:physiology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010457:Peptidoglycan; D014640:Vancomycin