Third-Generation Cephalosporin Resistance and Associated Discordant Antibiotic Treatment in Emergency Department Febrile Urinary Tract Infections

Abstract

Study objective: 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 blactamases. 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.Methods: 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.Results: 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 b-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). Conclusion: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. [

A multicenter analysis of trends in resistance in urinary Enterobacterales isolates from ambulatory patients in the United States: 2011–2020

“…Outpatient UTIs caused by Enterobacterales isolates with an ESBL-producing phenotype are associated with a sevenfold increase in clinical failure compared with non-ESBL-producing isolates [ 9 ], and inpatients with UTIs due to ESBL-producing isolates have a longer hospital length of stay, higher mortality, and higher rates of re-admission [ 22 , 23 ]. Due to the morbidity and mortality associated with UTIs due to ESBL-producing organisms, prompt, effective treatment is essential to improving patient outcomes.…”

“…Due to the morbidity and mortality associated with UTIs due to ESBL-producing organisms, prompt, effective treatment is essential to improving patient outcomes. However, discordant empiric therapy is common in both outpatients and inpatients with UTIs caused by isolates with an ESBL-producing phenotype [ 8 , 9 , 23 ]. As shown in our analyses, Enterobacterales isolates with an ESBL-producing phenotype are often highly resistant to oral agents commonly used to treat UTIs.…”

Short- and long-term mortality in patients with urosepsis caused by Escherichia coli susceptible and resistant to 3rd generation cephalosporins

“…Thirty-day mortality in our cohort was 8.6%. In the Swedish cohort mortality was higher and reached 15% [26], in a French cohort mortality was 9.5% [27], and in an American cohort between 8 and 12% [28]. Higher mortality rates have been observed when assessing other Enterobacteriaceae causing urosepsis such as K. pneumonia.…”

Clinical Outcome of Discordant Empirical Therapy and Risk Factors Associated to Treatment Failure in Children Hospitalized for Urinary Tract Infections

“…However, in-vivo effectiveness may be different from in-vitro results considering that antibiotic concentrations in urinary tract are often higher than can be achieved in blood [ 17 ]. Clinical improvement has been reported in adult patients affected by UTIs despite discordant therapy, questioning the need of using new broad-spectrum antibiotics as first-line treatment [ 18 , 19 ]. However, data on pediatric population are lacking; thus, the real consequences in everyday clinical practice of the increasing antibiotic resistance in pediatric UTIs are still unclear.…”