Polymicrobial Complexity Rather than Glycemic Control Is Associated with Multidrug Resistance in Diabetic Foot Infections

To investigate factors associated with multidrug resistance (MDR) in diabetes-related foot infections (DFIs), focusing on polymicrobial infection and glycated hemoglobin (HbA1c). This retrospective single-center study included culture-positive deep-tissue biopsy specimens collected during 2025. Consecutive positive biopsies from the same patient were grouped into episodes when successive samples were obtained ≤7 days apart. MDR was assessed using organism-specific antimicrobial categories, counting resistant results and excluding expected resistance phenotypes. Logistic regression used patient-clustered robust standard errors. HbA1c was evaluated in a secondary model restricted to measurements within ±30 days of sampling. The 191 culture-positive biopsies yielded 175 episodes from 150 patients; 43 episodes (24.6%) were polymicrobial. The most frequently recovered species were Staphylococcus aureus (35.4% of episodes), Pseudomonas aeruginosa (20.6%) and Enterococcus faecalis (14.9%). Among 157 MDR-evaluable episodes, 49 (31.2%) were MDR-positive. MDR occurred in 46.5% of polymicrobial versus 25.4% of monomicrobial episodes (crude OR 2.55; p = 0.020). Polymicrobial infection remained associated with MDR after adjustment for Gram-negative involvement, age and sex (aOR 4.52, 95% CI 1.91–10.72). In the HbA1c-adjusted model (94 episodes; 85 patients), polymicrobial infection remained associated with MDR (aOR 4.04, 95% CI 1.38–11.84), whereas HbA1c was not significantly associated with MDR (aOR 0.91 per 1% increase, 95% CI 0.69–1.20). Polymicrobial infection was associated with MDR, although unmeasured clinical confounding limits interpretation. The HbA1c findings remain inconclusive because of limited precision. These associations require confirmation in larger studies incorporating detailed clinical exposures and wound characteristics.