Five-Year Evolution of the Microbiological Landscape of Diabetic Foot Infections (2021–2025): Rising Polymicrobial Gram-Negative Predominance and Emergence of Resistant Enterobacterales at a Single Large-Volume Outpatient Centre

Background/Objectives: Diabetic foot infections (DFI) drive most non-traumatic lower-limb amputations, and empirical regimens must track local microbiology, which is itself evolving under broad-spectrum antibiotic pressure. Methods: We retrospectively analysed all consecutive bacterial cultures from clinically infected diabetic foot lesions at a single Polish outpatient centre over 2021–2025. Isolates were identified by MALDI-TOF mass spectrometry and susceptibility was interpreted under contemporaneous EUCAST breakpoints (v12.0–v15.0). Results: A total of 274 cultures yielded 443 isolates (polymicrobial index 1.62). Staphylococcus aureus remained the most common pathogen but fell from 55.0% to 38.9% of cultures, while Enterobacterales rose from 36.1% to 47.7% of all isolates. Proteus mirabilis and Streptococcus agalactiae emerged as major contributors, and Enterobacter hormaechei showed an apparent increase (the apparent rise in E. hormaechei reflects, at least in part, improved species-level identification rather than a true increase in incidence). Methicillin-resistant S. aureus was first documented in 2025 (6/38; 15.8%). P. mirabilis showed deteriorating activity against trimethoprim–sulfamethoxazole and ciprofloxacin, the first meropenem-resistant isolate appeared in 2025, and two carbapenem-non-susceptible Enterobacterales were also detected (2/18 carbapenem-tested isolates in 2025; 11%). Conclusions: The DFI profile has shifted from an S. aureus-dominated Gram-positive ecology toward a polymicrobial, increasingly Gram-negative one, with the first documentation of MRSA (on reintroduction of routine oxacillin testing) and of carbapenem-non-susceptible Enterobacterales. Empirical policy for moderate-to-severe DFI should reliably cover Enterobacterales and methicillin-resistant Gram-positives while preserving carbapenems and glycopeptides through active stewardship.