Evaluating outcomes associated with revised fluoroquinolone breakpoints for Enterobacterales urinary tract infections: A retrospective cohort study

Purpose: In 2019, minimum inhibitory concentration (MIC) breakpoints of ciprofloxacin and levofloxacin for Enterobacterales were lowered. This study sought to determine whether there is a correlation between MIC and outcomes in those receiving fluoroquinolones (FQs) for urinary tract infections (UTIs) caused by Enterobacterales pathogens. Methods: This was a retrospective study of adult patients treated with ciprofloxacin or levofloxacin for a UTI caused by an Enterobacterales pathogen. Patients were placed into low MIC (ciprofloxacin: ≤ 0.25 mcg/mL; levofloxacin ≤ 0.5 mcg/mL), intermediate MIC (ciprofloxacin: 0.5–2 mcg/mL; levofloxacin: 1–4 mcg/mL), or high MIC groups (ciprofloxacin: > 2 mcg/mL; levofloxacin: > 4 mcg/mL). The primary outcome was UTI recurrence, defined as hospital admission, emergency department or clinic visit due to UTI, or antibiotic prescription within 28 days of FQ initiation. Results: A total of 1022 patients were included: 887, 75, and 60 with a low, intermediate, and high MIC, respectively. UTI recurrence within 28 days occurred most frequently in the high MIC group (20.5% vs. 25.3% vs. 60%; P < 0.01). Risk factors for UTI recurrence identified by multivariable analysis were those with a high MIC (high vs. low MIC: OR 5.20, 95% CI 2.99–9.05, P < 0.01; high vs. intermediate MIC: OR 4.72, 95%CI 2.22–10.03, P < 0.01), a complicated UTI (OR 1.85, 95% CI 1.35–2.54; P < 0.01), a history of recurrent UTIs (OR 1.84, 95% CI 1.29–2.62; P < 0.01), or a respiratory disorder (OR 1.58, 95% CI 1.04–2.42; P = 0.03). Conclusion: This study supports separate, less stringent FQ MIC breakpoint interpretive criteria for UTIs caused by Enterobacterales pathogens.