Association Between Clinical Frailty and Antibiotic Resistance Among Older Patients with Fever in the Emergency Department

<b>Background</b>: Frailty may predispose older adults to antibiotic-resistant infections; however, evidence in emergency department (ED) patients with fever remains limited. <b>Methods</b>: We conducted a retrospective multicenter cohort study of 544 ED patients aged ≥65 years with fever (tympanic temperature ≥ 37.5 °C) between August and October 2023. The cohort included 234 men and 310 women. Frailty was assessed using the Clinical Frailty Scale (CFS) and categorized as robust (CFS 1-3), pre-frail (CFS 4-5), or frail (CFS 6-9). ED-initiated microbiological cultures were obtained in 329/544 (60.5%) patients. The primary outcome was the detection of antibiotic-resistant isolates among culture-tested patients. <b>Results</b>: Among culture-tested patients (<i>n</i> = 329), antibiotic-resistant isolates were detected in 65/329 (19.8%), with a graded increase across frailty strata: robust 13/121 (10.7%), pre-frail 16/88 (18.2%), and frail 36/120 (30.0%). In multivariable logistic regression restricted to culture-tested patients, frailty was independently associated with resistant infection (adjusted OR 2.84, 95% CI 1.15-7.04, <i>p</i> = 0.024). Frail patients also experienced greater therapeutic complexity, including higher rates of antibiotic regimen modification (68.1% vs. 54.5%) and longer antibiotic duration (median, 11 vs. 8 days), as well as worse clinical outcomes, including higher ICU admission (37.7% vs. 17.8%) and in-hospital mortality (7.2% vs. 1.8%) compared with robust patients. <b>Conclusions</b>: Frailty is independently associated with antibiotic-resistant infections in older ED patients with fever. Integrating frailty assessment into ED protocols can enhance risk stratification, inform empirical antibiotic selection, and antimicrobial stewardship strategies.