Serum vitamin D, innate immunity markers, and biofilm presence as determinants of therapeutic strategies in diabetic foot infections: A comparative cross-sectional study

Background Severe diabetic foot infections (DFIs) often require surgical management (SM), whereas less severe infections may be managed medically (MM). Vitamin D, its receptor (VDR), and LL-37 play key roles in innate immunity, wound healing, and antimicrobial defense. Aim To determine the association between serum vitamin D, VDR, and LL-37 levels and the prevalence of biofilm-forming bacteria in SM and MM in patients with DFIs. Methods 207 patients with DFIs were recruited from the Department of General Surgery, Kasturba Hospital, Manipal, India, between September 2022 and September 2025. Treatment allocation (SM or MM) was determined by the attending surgeons based on DFI severity. At 24 h after treatment initiation, blood samples were collected for vitamin D assessment (electrochemiluminescence immunoassay) and VDR and LL-37 quantification using enzyme-linked immunosorbent assay. Biofilm formation was analyzed using the tissue culture plate method. Results Of the 207 participants, 169 (81.64%) required SM and 38 (18.36%) received MM. Patients with SM had significantly lower median levels of vitamin D (12.6 vs. 24.3 ng/mL), VDR (0.69 vs. 1.34 ng/mL), and LL-37 (1.28 vs. 2.46 ng/mL) compared to those with MM (all p < 0.001). SM was significantly associated with DFI severity ( p = 0.004) and CRP levels ( p = 0.034) after adjusting confounders. Among the 182 biofilm-forming bacterial isolates, 87.4% were isolated from patients undergoing SM and 12.6% from those receiving MM ( p < 0.001). Summary Lower serum vitamin D, VDR, and LL-37 levels, together with a higher prevalence of biofilm-forming bacteria, were associated with greater DFI severity and an increased likelihood of SM.