OBJECTIVE To study the relative frequency of bacterial isolates cultured from community-acquired foot infections and assess their comparative in vitro susceptibility to sparfloxacin, levofloxacin, and eight other commonly used oral antimicrobial agents. RESEARCH DESIGN AND METHODS This is a prospective study in which the infected wounds of 25 consecutive diabetic patients seen by one of the authors were cultured as they entered the hospital. Isolates were stored and tested for susceptibility to 10 oral antimicrobial agents using the agar dilution method. RESULTS Staphylococcus aurcus was the most common isolate (76% of patients), including methicillin-resistant S. aurcus (MRSA) in 5 of 25 (20%) patient wounds. Streptococci, enterococci, Enterobacteriaceae, and anaerobes were also present in ≥40% of patient wounds. Sparfloxacin and levofloxacin were the most active agents tested with activity against ≥88% of isolates. Isolates resistant to sparfloxacin and levofloxacin included MRSA, enterococci, and some anaerobes. When analyzed by prior exposure to antibiotics, patients who had previously received oral antibiotics were more likely to have MRSA, enterococci, and Pseudomonas aeruginosa isolated and less likely to have Enterobacteriaceae and anaerobes isolated from their wounds. CONCLUSIONS MRSA and enterococci are now a common cause of diabetic foot infections, and the increased prevalence may be due to antimicrobial use. These wounds may require use of combined antimicrobial therapy for initial outpatient management. The new fluoroquinolones, sparfloxacin and levofloxacin, were the most active oral agents tested.