1. Intro duc tion 2. Enteroba cter iaceae 3. Infec tio ns due to ESBL-producing organisms: clinical features and risk factors 4. b-Lactamase-mediated resistance among gram negative bacteria 5. Epid emio log y and glob al spread of ESBLs 6. Epid emio log y and glob al spread of CPEs 7. Trea tme nt of infe ctio ns due to ESBL-producers and/or CPE producers 8. Other agents 9. Conclusion 10. Summary 11. Ex per t opini on Review Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum b-lactamases and carbapenemases) Joseph P Lynch III † , Nina M Clark & George G Zhanel † The David Geffen School of Medicine at UCLA, Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Los Angeles, CA, USA Introduction: Bacteria withi n the fami ly Enterobacteriaceae are important pathogens in nosocomial and community settings. Over the past two decades, antimicrobia l resistance among Enterobacte riaceae dramatically escalated worldwide. The authors review the mechanisms of antimicrobial resistance amon g Ente roba cter iace ae, epid emio logy and glob al spre ad of resi stance elements and discuss therapeutic options. Areas covered: An exhaustive search for literature relating to Enterobacteria- ceae was performed using PubMed, using the following key words: Entero- bacteriaceae; Klebsiella pneumoniae; Escherichia coli; antimicrobial resistance; plasmids; globa l epidem iology ; carbap enema ses (CPEs) ; extend ed spectr um b-lactamases (ESBLs) and multidrug resistance (MDR). Exper t opinio n: Ent erobacteria ceae are inhabi tants of intes tinal flora and spr ead eas ily amo ng humans (via han d car ria ge, con tamina ted foo d or wate r or environmental source s). Ant imicrobial res ist anc e may develop via plasmids, tra nsposons or other mobile resistance elements. Mutati ons conf err ing res istance typ ica lly increa se over time; the rat e of increas e is amplified by sel ect ion pressure fro m antibioti c use. Factor s that enh anc e spr ead of antimicrobial resist anc e include: cro wdi ng; lack of hygi ene ; overuse and over-the-counter use of antibiotics; tourism; refugees and international tra vel. Clonal spre ad of resistant org ani sms among hos pit als, geo graphic regions and continents has globally fuele d the explosive rise in resis tance . The eme rgence and wide spread dissemination of MDR clo nes con tai ning novel resistance eleme nts (particularly ESBLs and CPEs) has greatly limited therapeutic options. In some cases, infections due to MDR Enterobacteriaceae are untrea tab le with existing ant imicrobial agents. The aut hor s discus s current and future therapeutic options for difficult-to-treat infections due to these organisms. Keywords: antimicrobial resistance, carbapenemases, Enterobacteriaceae, extended spectrum b-lactamases, multidrug resistance Expert Opin. Pharmacother. (2013) 14 (2):199-210 1. Introduction Over the past two to three decades, resistance rates to a variety of antibiotics have drama ticall y escal ated withi n the Unit ed States and globa lly [1-4]. Mecha nisms responsible for antibiotic resistance include: enzymatic inactivation or modification of antibiotics; alteration in the bacterial target site(s); permeability barriers to influx of antibiotics; active efflux pumps (that extrude antibiotics from bacterial cells) and 10.1517/14656566.2013.763030 © 2013 Informa UK, Ltd. ISSN 1465-6566, e-ISSN 1744-7666 199 All rights reserved: reproduction in whole or in part not permitted E x p e r t O p i n . P h a r m a c o t h e r . D o w n l o a d e d f r o m i n f o r m a h e a l t h c a r e . c o m b y H I N A R I o n 0 1 / 3 1 / 1 3 F o r p e r s o n a l u s e o n l y .
