Escherichia coli remains one of the most frequent causes of nosocomial and community-acquired bacterial infections including urinary tract infections, enteric infections, and systemic infections in humans. Extra-intestinal pathogenic E. coli or ExPEC had emerged during the 2000s as an important player in the resistance to antibiotics, especially to the cephalosporins and fluoroquinolones. Most importantly among ExPEC, is the increasing recognition of isolates producing "newer β-lactamases" that consist of plasmidmediated AmpC β-lactamases (e.g. CMY), extended-spectrum β-lactamases (e.g. CTX-M), and carbapenemases (e.g. NDM, KPC and OXA-48). Since the mid 2000's, E. coli that produce CTX-M enzymes (especially CTX-M-15), have emerged worldwide as important causes of community-associated urinary tract (UTIs) and blood stream infections. Community-associated acquisition and infections due to enterobacteria with plasmid-mediated AmpC β-lactamases are a relatively recent phenomenon and have been described in Canada and USA. Empiric antibiotic coverage for these resistant organisms should be considered in community patients presenting with sepsis involving the urinary tract especially if a patient recently traveled to a high-risk area. If this emerging public health threat is ignored, it is possible that the medical community may be forced in the near future to use the carbapenems as the first choice for the empirical treatment of serious infections associated with urinary tract infections originating from the community.