| Abstract: |
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). |
| Keywords: |
antibiotic agent; unclassified drug; clinical trial; review; drug efficacy; drug potentiation; nonhuman; drug targeting; medical decision making; unindexed drug; liver toxicity; nephrotoxicity; models, biological; hemolysis; prevalence; drug potency; drug structure; drug design; bacterial strain; antiinfective agent; bacterial protein; antibiotic resistance; anti-bacterial agents; bacterial proteins; drug mechanism; protein synthesis; substrate specificity; urinary tract infection; gentamicin; enterococcus; staphylococcus aureus; vancomycin resistance; gram-positive bacterial infections; staphylococcal infections; linezolid; vancomycin; bacterial infection; glycopeptide; multidrug resistance; cyclopeptide; membrane permeability; sensitization; skin infection; resistance; drug resistance, multiple, bacterial; antimicrobial activity; gram positive bacterium; soft tissue infection; antibiotic; daptomycin; teicoplanin; imipenem; bacteriophage; dalfopristin plus quinupristin; chloramphenicol; dalfopristin; quinupristin; biphenyl derivative; peptidoglycan; oxazolidinone derivative; genes, bacterial; polypeptide antibiotic agent; lipopeptide; gram-positive bacteria; streptogramin; humans; human; vancomycin derivative; d,l-α-peptide; glycylcycline; lipoglycodepsipeptide; orthosomysin; oxazolidinone; peptidoglycan (pg); s-prolinol; sproc5; vancomycin-resistant enterococci (vre); vancomycin-resistant s. aureus (vrsa); vancomysin-intermediate s. aureus (visa); avoparcin; beta lactam antibiotic; chloroorienticin a; evernimicin; glycycycline derivative; oritavancin; orthosomycin derivative; prolinol derivative; ramoplanin; tigecycline
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