| Summary: | Gram positive pathogens are a significant cause of healthcare-associated infections, with <i>Staphylococci</i> and <i>Enterococci</i> being the most prevalent ones. Vancomycin, a last resort glycopeptide, is used to fight these bacteria but the emergence of resistance against this drug leaves some patients with few therapeutic options. To counter this issue, new generations of antibiotics have been developed but resistance has already been reported. In this article, we review the strategies in place or in development to counter vancomycin-resistant pathogens. First, an overview of traditional antimicrobials already on the market or in the preclinical or clinical pipeline used individually or in combination is summarized. The second part focuses on the non-traditional antimicrobials, such as antimicrobial peptides, bacteriophages and nanoparticles. The conclusion is that there is hitherto no substitute equivalent to vancomycin. However, promising strategies based on drugs with multiple mechanisms of action and treatments based on bacteriophages possibly combined with conventional antibiotics are hoped to provide treatment options for vancomycin-resistant Gram-positive pathogens.
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