Optimizing therapy for vancomycin-resistant enterococci (VRE)

Enterococci are gram-positive, facultative bacteria with low intrinsic virulence but capable of causing a diverse variety of infections such as bacteremia with or without endocarditis, and intra-abdominal, wound, and genitourinary infection. During the past 2 decades the incidence of hospital-acquired enterococcal infection has significantly risen and is increasingly due to multidrug-resistant strains, primarily to the coacquisition of genetic determinants that encode for the stable expression of high-level beta-lactam, aminoglycoside, and glycopeptide resistance. Because enterococci constitute part of the normal colonizing flora, careful clinical interpretation of cultures that grow enterococci is paramount to avoid unnecessary and potentially deleterious antimicrobial therapy. Traditional antimicrobial treatment for ampicillin- and glycopeptide-susceptible enterococcal infection remains a penicillin-, ampicillin-, semisynthetic penicillin-based regimen, or vancomycin in a penicillin-intolerant individual. The need for a bactericidal combination with a cell-wall active agent combined with an aminoglycoside is most supported for native- or prosthetic valve endocarditis but is unproven for the majority of infections due to enterococci. The emergence of vancomycin-resistant enterococci prompted the clinical development of several novel and modified antimicrobial compounds approved for VRE infection (quinupristin-dalfopristin, linezolid) and several approved for non-VRE indications (daptomycin, tigecycline). There is a paucity of comparative clinical trial data with these new agents, although linezolid, based upon its efficacy and tolerability, appears to be the cornerstone of current treatment approaches. Despite a relatively short period of clinical use, enterococcal resistance has now been described for quinupristin-dalfopristin and linezolid and more recently even for daptomycin and tigecycline. Moreover, the optimal treatment of endocarditis due to VRE strains is unknown because, with the exception of daptomycin, current treatment options only yield bacteriostasis. Nonantimicrobial measures to treat VRE infection, such as foreign body removal and percutaneous or surgical drainage of close-spaced infection, reduce both the need for and the duration of anti-enterococcal treatment and the emergence of resistance to the newer antimicrobials.