title: The rapid spread of carbapenem-resistant Enterobacteriaceae.
abstract: Carbapenems, our one-time silver bullet for multidrug resistant bacterial infections, are now threatened by widespread dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Successful expansion of Enterobacteriaceae clonal groups and frequent horizontal gene transfer of carbapenemase expressing plasmids are causing increasing carbapenem resistance. Recent advances in genetic and phenotypic detection facilitate global surveillance of CRE diversity and prevalence. In particular, whole genome sequencing enabled efficient tracking, annotation, and study of genetic elements colocalized with carbapenemase genes on chromosomes and on plasmids. Improved characterization helps detail the co-occurrence of other antibiotic resistance genes in CRE isolates and helps identify pan-drug resistance mechanisms. The novel β-lactamase inhibitor, avibactam, combined with ceftazidime or aztreonam, is a promising CRE treatment compared to current colistin or tigecycline regimens. To halt increasing CRE-associated morbidity and mortality, we must continue quality, cooperative monitoring and urgently investigate novel treatments.
authors.affiliation: Center for Genome Sciences and System Biology, Washington University School of Medicine, 4515 McKinley Avenue, Campus Box 8510, St. Louis, MO 63110, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Potter
authors.affiliation: Center for Genome Sciences and System Biology, Washington University School of Medicine, 4515 McKinley Avenue, Campus Box 8510, St. Louis, MO 63110, USA.
authors.forename: Alaric W
authors.initials: AW
authors.lastname: D'Souza
authors.affiliation: Center for Genome Sciences and System Biology, Washington University School of Medicine, 4515 McKinley Avenue, Campus Box 8510, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO 63110, USA; Department of Biomedical Engineering, Washington University in Saint Louis, 1 Brookings Drive, St. Louis, MO 63130, USA; Department of Molecular Microbiology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, USA. Electronic address: dantas@wustl.edu.
authors.forename: Gautam
authors.initials: G
authors.lastname: Dantas
mesh_terms: D001426:Bacterial Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D000073182:Carbapenem-Resistant Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity; D015780:Carbapenems / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004359:Drug Therapy, Combination; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology / Q000635:transmission*; D062665:Epidemiological Monitoring; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000145:classification / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D012093:Replicon; D018440:beta-Lactam Resistance / Q000235:genetics*; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*; D001618:beta-Lactamases / Q000145:classification / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015780:Carbapenems; D007527:Isoenzymes; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases; C063912:carbapenemase
keywords: Antibiotic resistance; Carbapenem Resistant Enterobacteriaceae; Horizontal gene transfer