Comparison of Cefazolin and Ceftriaxone Enterobacterales Susceptibilities for Inpatient Treatment of Urinary Tract Infections and Risk of Hospital-Onset Clostridioides difficile Infection

Abstract

Purpose: Urinary tract infection (UTI) is the second most common indication for antibiotic therapy among inpatients in the United States. Ceftriaxone, a third-generation cephalosporin, is habitually chosen to treat inpatient UTIs due to familiarity, cost and perceived safety. However, third-generation cephalosporins increase the risk of healthcare facility-onset Clostridioides difficile infection (HOCDI) more than any other antibiotic group, while no statistical risk exists for first-generation cephalosporins. Recent evidence comparing Enterobacterales susceptibility for first- and third-generation cephalosporins in urinary specimens in the United States does not exist. This analysis assesses comparative activity of cefazolin and ceftriaxone for Enterobacterales urinary isolates and incidence of HOCDI to determine the usefulness of cefazolin as an empiric agent to manage inpatient UTI and limit ceftriaxone collateral damage.Methods: This is a retrospective single center observational study. Microbiologic susceptibility data was analyzed for E. coli, K. pneumoniae, and P. mirabilis urinary specimens taken from adult inpatients admitted January 1, 2022 to December 31, 2022. Primary outcome is incidence of E. coli, K. pneumoniae, and P. mirabilis susceptibility to cefazolin in uncomplicated UTI (MIC < 16 mcg/mL). Secondary outcomes include susceptibility for complicated UTI and HOCDI risk associated with cefazolin and ceftriaxone. A larger time frame, January 1, 2016 to December 31, 2022, was used to assess HOCDI risk associated with cefazolin and ceftriaxone. HOCDI risk assessment included adults administered at least one dose of either cefazolin or ceftriaxone during a minimum of four-day hospitalization.Findings: A total of 1150 urine samples were identified as E. coli, K. pneumoniae, and P. mirabilis in 2022. Susceptibility to cefazolin was observed in 1064/1150 (92.5%) isolates using the MIC breakpoint for uncomplicated UTI, and to ceftriaxone in 1115/1150 (97.0%) isolates (p < 0.001). From 2016-2022, either cefazolin or ceftriaxone was administered in 26,462 inpatient admissions with an HOCDI diagnoses occurring in 89 admissions. HOCDI developed in 78 admissions (0.40%) with ceftriaxone exposure and 11 cases (0.15%) developed in cefazolin exposed admissions (p < 0.001, adjusted OR 2.44, 95% CI 1.25 – 4.76).Implications: Cefazolin demonstrates high susceptibility for uropathogens commonly implicated in uncomplicated UTI, the predominant UTI managed inpatient. While ceftriaxone demonstrates a higher susceptibility rate against these common uropathogens, it more than doubles the risk for HOCDI compared to cefazolin. For institutions evaluating opportunities to reduce ceftriaxone use to limit associated collateral damage like HOCDI, use of cefazolin for uncomplicated urinary tract infection may be evaluated using local susceptibility data.