Therapeutic Options for Infections due to vanB Genotype Vancomycin-Resistant Enterococci Niccolo ` Riccardi, 1 Jacopo Monticelli, 2 Roberta Maria Antonello, 3 Gustavo Di Lallo, 4 Domenico Frezza, 4 Roberto Luzzati, 5 and Stefano Di Bella 5 Enterococci are ubiquitous, facultative, anaerobic Gram-positive bacteria that mainly reside, as part of the normal microbiota, in the gastrointestinal tracts of several animal species, including humans. These bacteria have the capability to turn from a normal gut commensal organism to an invasive pathogen in patients debilitated by prolonged hospitalization, concurrent illnesses, and/or exposed to broad-spectrum antibiotics. The majority of vancomycin-resistant enterococcus (VRE) infections are linked to the vanA genotype; however, outbreaks caused by vanB-type VREs have been increasingly reported, representing a new chal- lenge for effective antimicrobial treatment. Teicoplanin, daptomycin, fosfomycin, and linezolid are useful antimicrobials for infections due to vanB enterococci. In addition, new drugs have been developed (e.g., dalbavancin, telavancin, and tedizolid), new molecules will soon be available (e.g., eravacycline, omada- cycline, and oritavancin), and new treatment strategies are progressively being used in clinical practice (e.g., combination therapies and bacteriophages). The aim of this article is to discuss the pathogenesis of infections due to enterococci harboring the vanB operon (vanBVRE) and their therapeutic, state-of-the-art, and future treatment options and provide a comprehensive and easy to use review for clinical purposes. Keywords: VRE, antibiotics, infections Introduction E nterococci are ubiquitous, facultative, anaerobic Gram-positive bacteria that mainly reside, as part of the normal microbiota, in the gastrointestinal tracts of almost all animals, including humans. 1,2 Since the first description as a human pathogen in 1899, and recognition as a causative agent of infective endocarditis, En- terococcus species (spp.) has been found to be responsible for a wide range of other human life-threatening infections such as sepsis, endocarditis, meningitis, urinary tract infections, and neonatal infections. 3–6 The genus Enterococcus seems to have the capability to turn from a normal gut commensal organism into an invasive pathogen in patients debilitated by prolonged hospitalization and/or affected by concurrent illnesses and/or exposed to broad-spectrum antibiotics. 7,8 The potential extensive resistance to a broad range of anti- biotics confers on this group of pathogens a selective advantage over other bacteria composing the human microbiota, thus fa- cilitating their nosocomial spread under antimicrobial pressure. 9 Indeed, E. faecium displays an almost universal intrin- sic resistance to penicillin and beta-lactams with intrin- sic cell wall impermeability to aminoglycosides, while E. gallinarum and E. casseliflavus are known to be in- trinsically resistant to vancomycin. 7–10 The first report of vancomycin-resistant enterococcus (VRE) dates back to 1986; however, outbreaks from this organism are still a current problem, leading the World Health Organization (WHO) to enlist vancomycin-resistant E. faecium within the priority two group of bacteria that urgently need new antibiotics. 11–13 There are many types of genotypic and phenotypic re- sistance mechanisms to glycopeptides displayed by En- terococcus spp., which differ from each other in the level and range of resistance to glycopeptides and in transfer- ability to other bacteria. 14,15 Although the majority of VRE-attributable infections are linked to the vanA genotype, outbreaks caused by vanB- type VRE have been increasingly reported, representing a new challenge for effective antimicrobial treatment. 16 1 Department of Infectious–Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy. 2 Hospital Direction, AULSS6 Euganea Ospedali Riuniti Padova Sud, Monselice, Italy. 3 School of Medicine, University of Trieste, Trieste, Italy. 4 Department of Biology, University of Rome ‘‘Tor Vergata,’’ Rome, Italy. 5 Infectious Diseases Department, Azienda Sanitaria Universitaria Integrata di Trieste, Trieste, Italy. MICROBIAL DRUG RESISTANCE Volume 00, Number 00, 2020 ª Mary Ann Liebert, Inc. DOI: 10.1089/mdr.2020.0171 1 Downloaded by Cornell University package NERL from www.liebertpub.com at 08/17/20. For personal use only.