Data on the in vitro susceptibility of urinary isolates of Escherichia coli to first- and second-line empirically prescribed oral antimicrobials were published in the International Journal of Antimicrobial Agents; researchers highlighted that prudent use and monitoring of antimicrobial agents is imperative to help preserve their utility.

As part of the CANWARD surveillance study, 2035 isolates of E coli from urine specimens were collected from outpatients at Canadian medical clinics and hospital emergency departments from 2007 to 2016. Minimum inhibitory concentrations were interpreted using CLSI M100 criteria.

Between 2007 and 2016, the antibacterial agents found to be most active were fosfomycin (99.2% of isolates susceptible), nitrofurantoin (97.5%), and cephalexin (93.6%). The less active agents tested were amoxicillin-clavulanate (85.6%), ciprofloxacin (83.0%), and trimethoprim-sulfamethoxazole (77.0%). Researchers noted that during this period, trimethoprim-sulfamethoxazole, cephalexin, and ciprofloxacin demonstrated a trend of decreasing susceptibility against isolates of E coli. The annual percentages of isolates from 2007 to 2016 that were extended-spectrum β-lactamase (ESBL)-positive or that demonstrated multidrug-resistant (MDR) phenotypes, increased from 0.8% to 10.1%, and from 9.7% to 16.5%, respectively. There was a decline in the annual frequency of AmpC-positive isolates from a high of 3.2% in 2008 to 0.7% in 2016.

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The most common MDR phenotype of E coli accounted for 12.7% of all MDR phenotypes and was nonsusceptible to amoxicillin-clavulanate, ciprofloxacin, and trimethoprim-sulfamethoxazole. The rates of susceptibility were higher for fosfomycin than for all 5 other oral agents tested against ESBL-positive (96.1% susceptible) and MDR isolates (95.1%), and equal to susceptibility to nitrofurantoin (96.4%) against AmpC-positive isolates.

The study authors noted that calculated rates of resistance in this study may be overestimated because outpatients as patients with complicated urinary tract infections, with comorbidity or recent antimicrobial exposure, or with healthcare-related infections may be present in the data set. Also, researchers could not account for the possible inclusion of isolates representing asymptomatic bacteriuria in the collection, which may also influence the reported resistance rates. In addition, the study investigators acknowledged that outpatients may have received antimicrobials in the weeks before their current urinary tract infection, which also might have increased the isolation of resistant bacterial pathogens.

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According to the study investigators, E coli was the most common bacterial pathogen isolated from urine when culture was performed, and the annual prevalence of Enterobacteriaceae, Pseudomonas aeruginosa, and gram-positive cocci was consistent from 2007 to 2016. They also concluded that in vitro susceptibility to trimethoprim-sulfamethoxazole was <80% for 8 of the 10 years studied, and “its use as empirical therapy should be reviewed based upon local antibiograms.” Fosfomycin and nitrofurantoin were the most active agents tested, and on this basis, recent data generated by others, and expert literature reviews, the researchers stated, “the activity of fosfomycin and nitrofurantoin remain high for most cases of E. coli urinary tract infections, including infections caused by MDR isolates of E. coli.”


Karlowsky JA, Lagacé-Wiens PRS, Adam HJ, et al. In vitro susceptibility of urinary isolates of Escherichia coli to first- and second-line empirically prescribed oral antimicrobial agents: CANWARD surveillance study results for Canadian outpatients from 2007 to 2016 [published online April 26, 2019]. Int J Antimicrob Agents. doi:10.1016/j.ijantimicag.2019.04.012