Third-Generation Cephalosporin Resistance and Associated Discordant Antibiotic Treatment in Emergency Department...

Third-generation cephalosporin-resistant (3GCR) Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis (EKP) are an increasingly common cause of community-onset urinary tract infections (UTIs) in the United States. The 3GCR antimicrobial resistance pattern in these Enterobacterales species is most commonly due to production of extended-spectrum β-lactamases. We sought to provide contemporary, emergency department (ED)-focused data on 3GCR-EKP UTI regional prevalence, presentation, antibiotic susceptibility, and empiric treatment patterns, and outcomes.

We performed a retrospective cohort study of all adults admitted with a febrile UTI at 21 Kaiser Permanente Northern California EDs between January 2017 and June 2019. Inclusion criteria included fever; admitting diagnosis of UTI, pyelonephritis, or sepsis; and ED urine culture with greater than 100,000 colony-forming units/mL of an EKP species. 3GCR was defined as in vitro resistance to ceftriaxone, ceftazidime, or both. 3GCR-EKP cases were compared with non-3GCR-EKP controls for the following: demographics, comorbidities, presenting clinical features, urinary isolate antimicrobial susceptibility, treatment, and clinical outcomes. The primary outcome measure was the rate of discordant initial empiric antibiotic treatment (administered within 6 hours of ED arrival) when compared with antimicrobial susceptibility testing. Secondary outcomes included hospital length of stay and 90-day mortality, adjusted for comorbidities and severity of illness.

There were 4,107 patients (median age 73 years and 35% men) who met study inclusion criteria. Of these patients, 530 (12.9%) had a 3GCR-EKP urinary tract infection. The proportion of subjects possessing risk factors for a health care-associated or extended-spectrum β-lactamase infection was 92.8% of case patients and 86.1% of controls. When comparing 3GCR-EKP case and non-3GCR-EKP control isolates, ciprofloxacin susceptibility rates were 21% versus 88%, and piperacillin/tazobactam susceptibility rates were 89% versus 97%, respectively. Initial empiric antibiotic therapy was discordant with antimicrobial susceptibility testing results in 63% of case patients versus 7% of controls (odds ratio 21.0; 95% confidence interval 16.9 to 26.0). The hospital length of stay was longer for 3GCR-EKP case patients, with an adjusted mean difference of 29.7 hours (95% CI 19.0 to 40.4). Ninety-day mortality was 12% in case patients versus 8% in controls (adjusted odds ratio 1.56; 95% confidence interval 1.07 to 2.28).

In this large, 2017 to 2019 Northern California ED study, nearly 13% of febrile EKP UTIs requiring hospitalization were caused by 3GCR-EKP, and in these cases, initial empiric therapy was often discordant with antimicrobial susceptibility testing. 3GCR-EKP infections were associated with a longer hospital length of stay and higher 90-day mortality. Similar data from other regions and for outpatient UTIs are needed.