title: Multidrug-Resistant Enterococcal Infections: New Compounds, Novel Antimicrobial Therapies?
abstract: Over the past two decades infections due to antibiotic-resistant bacteria have escalated world-wide, affecting patient morbidity, mortality, and health care costs. Among these bacteria, Enterococcus faecium and Enterococcus faecalis represent opportunistic nosocomial pathogens that cause difficult-to-treat infections because of intrinsic and acquired resistance to a plethora of antibiotics. In recent years, a number of novel antimicrobial compound classes have been discovered and developed that target Gram-positive bacteria, including E. faecium and E. faecalis. These new antibacterial agents include teixobactin (targeting lipid II and lipid III), lipopeptides derived from nisin (targeting lipid II), dimeric vancomycin analogues (targeting lipid II), sortase transpeptidase inhibitors (targeting the sortase enzyme), alanine racemase inhibitors, lipoteichoic acid synthesis inhibitors (targeting LtaS), various oxazolidinones (targeting the bacterial ribosome), and tarocins (interfering with teichoic acid biosynthesis). The targets of these novel compounds and mode of action make them very promising for further antimicrobial drug development and future treatment of Gram-positive bacterial infections. Here we review current knowledge of the most favorable anti-enterococcal compounds along with their implicated modes of action and efficacy in animal models to project their possible future use in the clinical setting.
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Roel M
authors.initials: RM
authors.lastname: van Harten
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Rob J L
authors.initials: RJL
authors.lastname: Willems
authors.affiliation: Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Nathaniel I
authors.initials: NI
authors.lastname: Martin
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: A.P.A.Hendrickx-4@umcutrecht.nl.
authors.forename: Antoni P A
authors.initials: APA
authors.lastname: Hendrickx
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000145:classification* / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000737:chemistry / Q000145:classification* / Q000627:therapeutic use*; D002462:Cell Membrane / Q000187:drug effects; D002473:Cell Wall / Q000187:drug effects; D003428:Cross Infection / Q000382:microbiology; D047630:Depsipeptides / Q000494:pharmacology; D055808:Drug Discovery; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D016983:Enterococcus / Q000187:drug effects*; D013293:Enterococcus faecalis / Q000187:drug effects; D016984:Enterococcus faecium / Q000187:drug effects; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D023421:Models, Animal; D009561:Nisin / Q000737:chemistry / Q000494:pharmacology; D014640:Vancomycin / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D047630:Depsipeptides; D009561:Nisin; D014640:Vancomycin; C000594838:teixobactin
keywords: Antibiotics; Antimicrobial therapy; Cell wall; Novel compounds