<span class="paragraphSection"><div class="boxTitle">Abstract</div><div class="boxTitle">Background.</div>Diabetic foot ulcers (DFUs) threaten limbs and prompt hospitalization. After hospitalization, remote-site invasive systemic infection related to DFU (DFU-ISI) may occur. The characteristics of DFU-ISIs and their effect on mortality risk have not been defined.<div class="boxTitle">Methods.</div>We conducted a retrospective cohort study of 819 diabetic patients hospitalized for treatment of 1212 unique DFUs during a 9-year period. We defined the index ulcer as that present at the first (index) DFU admission to our hospital. We defined DFU-ISI as a nonfoot infection that occurred after the index hospitalization and was caused by a microorganism concomitantly or previously cultured from the index ulcer. We determined the frequency, risk factors, and mortality risk associated with DFU-ISIs.<div class="boxTitle">Results.</div>After 1212 index DFU hospitalizations, 141 patients had 172 DFU-ISIs. Of the initial 141 DFU-ISIs, 64% were bacteremia, 13% deep abscesses, 10% pneumonia, 7% endocarditis, and 6% skeletal infections. Methicillin-resistant <span style="font-style:italic;">Staphylococcus aureus</span> (MRSA) caused 57% of the ISIs. Patients with initial DFU cultures yielding MRSA and protracted open ulcers had a high 24-month cumulative probability of DFU-ISI (31%) and all-cause mortality rate (13%). Analysis with Cox regression modeling showed that complicated ulcer healing (hazard ratio, 3.812; 95% confidence interval, 2.434–5.971) and initial DFU culture yielding MRSA (2.030; 1.452–2.838) predicted DFU-ISIs and that DFU-ISIs were associated with increased mortality risk (1.987; 1.106–3.568).<div class="boxTitle">Conclusions.</div>DFU-ISIs are important late complications of DFUs. Prevention of DFU-ISIs should be studied prospectively. Meanwhile, clinicians should aggressively incorporate treatment to accelerate ulcer healing and address MRSA into the care of diabetic patients with foot ulcers.</span>
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