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

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 health care 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 is limited. This analysis assessed the comparative activity of cefazolin and ceftriaxone for Enterobacterales urinary isolates and incidence of HOCDI to determine the usefulness of cefazolin as an empirical agent to manage inpatient UTI and limit ceftriaxone collateral damage. Methods: This was a retrospective single-center observational study. Microbiologic susceptibility data were analyzed for Escherichia coli, Klebsiella pneumoniae, , and Proteus mirabilis urinary specimens taken from adult inpatients admitted from January 1, 2022, to December 31, 2022. Primary outcome was incidence of E coli, K pneumoniae, , and P mirabilis susceptibility to cefazolin in uncomplicated UTI (MIC < 16 mu g/mL). Secondary outcomes include susceptibility for complicated UTI and HOCDI risk associated with cefazolin and ceftriaxone. 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 (92.5%) of 1150 isolates using the MIC breakpoint for uncomplicated UTI and to ceftriaxone in 1115 (97.0%) of 1150 isolates ( P < 0.001). From 2016 to 2022, either cefazolin or ceftriaxone was administered in 26,462 inpatient admissions, with 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 (adjusted odds ratio, 2.44; 95% CI, 1.25-4.76; P < 0.001). Implications: Cefazolin exhibits high susceptibility for uropathogens commonly implicated in cases of uncomplicated UTI, the most common UTI diagnosis among inpatients. Although ceftriaxone shows a higher susceptibility rate against these common uropathogens, it more than doubles the risk for HOCDI compared with cefazolin. For institutions evaluating opportunities to reduce ceftriaxone use to limit associated collateral damage such as HOCDI, use of cefazolin for uncomplicated UTI may be evaluated by using local susceptibility data.