Retrospective review from 11 Canadian hospitals showed increasing incidence of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae from 0.12 per 1,000 inpatient days during 2005 to 0.47 per 1,000 inpatient days during 2009. By 2009, susceptibility rates of ESBL-positive E. coli/K. pneumoniae were as follows: ciprofloxacin, 12.8%/9.0%; TMP/SMX, 32.9%/12.2%; and nitrofurantoin, 83.8%/10.3%. Nosocomial and nonnosocomial ESBL-producing E. coli isolates had similar susceptibility profiles, while nonnosocomial ESBL-producing K. pneumoniae was associated with decreased ciprofloxacin (P = 0.03) and nitrofurantoin (P < 0.001) susceptibilities.