The burden of antimicrobial resistance among urinary tract isolates of Escherichia coli in the United States in 2017

Abstract

Urinary tract infections (UTIs) caused by Escherichia coli have been historically managed with oral antibiotics including the cephalosporins, fluoroquinolones and trimethoprim-sulfamethoxazole. The use of these agents is being compromised by the increase in extended spectrum β-lactamase (ESBL)-producing organisms, mostly caused by the emergence and clonal expansion of E. coli multilocus sequence typing (ST) 131. In addition, ESBL isolates show co-resistance to many of oral agents. Management of UTIs caused by ESBL and fluoroquinolone-resistant organisms is becoming increasingly challenging to treat outside of the hospital setting with clinicians having to resort to intravenous agents. The aim of this study was to assess the prevalence of ESBL phenotypes and genotypes among UTI isolates of E. coli collected in the US during 2017 as well as the impact of co-resistance to oral agents such as the fluoroquinolones and trimethoprim-sulfamethoxazole. The national prevalence of ESBL phenotypes of E. coli was 15.7% and was geographically distributed across all nine Census regions. Levofloxacin and trimethoprim-sulfamethoxazole-resistance rates were ≥ 24% among all isolates and this co-resistance phenotype was considerably higher among isolates showing an ESBL phenotype (≥ 59.2%) and carrying blaCTX-M-15 (≥ 69.5%). The agents with the highest potency against UTI isolates of E. coli, including ESBL isolates showing cross-resistance across oral agents, were the intravenous carbapenems. The results of this study indicate that new oral options with the spectrum and potency similar to the intravenous carbapenems would address a significant unmet need for the treatment of UTIs in an era of emergence and clonal expansion of ESBL isolates resistant to several classes of antimicrobial agents, including oral options.

Genomic analysis of trimethoprim-resistant extraintestinal pathogenic Escherichia coli and recurrent urinary tract infections

“…3b). A high co-occurrence (>30 %) of trimethoprim and ESBL resistance was recently reported in the USA [77]. Furthermore, Mulder et al [78] demonstrated that previous use of extended-spectrum β-lactams in patients with UTIs was significantly associated with trimethoprim resistance.…”

Biochemical Characterization of QPX7728, a New Ultrabroad-Spectrum Beta-Lactamase Inhibitor of Serine and Metallo-Beta-Lactamases

“…Likewise, since none of these BLIs inhibit (18). Of note, none of these agents have oral formulations available for the treatment of infections due to serious or urgent resistant threats in setting where IV therapy is not available or desirable (19).…”

Safety and immunogenicity of an adjuvanted Escherichia coli adhesin vaccine in healthy women with and without histories of recurrent urinary tract infections: results from a first-in-human phase 1 study

“…More serious long-term outcomes include treatment failures, hospitalizations including prolonged stays and readmissions, bacteremia, severe sepsis, septic shock, in-hospital mortality, and the spread of antibiotic resistance. [5][6][7][8][9][10][11][12][13][14][15] For more than 20 years, healthcare providers have prescribed antibiotics with refills for patients with recurrent UTIs so that these individuals can self-treat as symptoms occur, without needing to confirm that bacteria are present in urine. 16 This treatment strategy empowers an individual to begin treatment earlier, so symptoms resolve faster.…”