Diabetic foot osteomyelitis (DFO) is among the most difficult complications of diabetes to treat. Bone infection is common in deep ulcers, it raises the risk of minor and major amputation, and it often requires both surgery and prolonged systemic antibiotics. Because antibiotics reach infected, poorly perfused bone in limited concentrations, interest has grown in delivering antibiotics directly to the surgical site using carriers such as antibiotic-loaded bone cement and absorbable calcium sulfate. This article summarizes what the published evidence shows and where it remains uncertain.
Why Local Delivery Is Appealing
Systemic antibiotics must travel through the bloodstream to reach bone, and in people with diabetes and peripheral artery disease that route may be compromised. Local carriers can produce very high antibiotic concentrations at the infected site while keeping blood levels low, which in theory limits systemic toxicity. Carriers also fill the dead space left after bone resection, a recognized site for persistent infection. Two main categories are used: non-absorbable polymethylmethacrylate (PMMA) bone cement, which typically requires later removal, and absorbable materials such as calcium sulfate, which dissolve over weeks. Both are generally used as an adjunct to surgical debridement and systemic therapy rather than as a replacement for either.
What the Reviews Conclude
A narrative review by Soldevila-Boixader and colleagues (Antibiotics, 2023) screened 388 records and included 19 studies of local antibiotics in diabetic foot infection. Only a handful were randomized trials; most local-delivery studies were retrospective, often lacked control groups, and could not be pooled. Results were mixed. One three-arm randomized trial of 25 patients found no added benefit from local antibiotics, whereas smaller trials and retrospective cohorts reported shorter healing times, and one retrospective study of 46 patients reported fewer recurrences without a shorter time to cure. The authors concluded that evidence is limited and heterogeneous, that several trials were probably underpowered, and that local antibiotics used alone, without systemic therapy, are essentially unstudied.
Reported adverse effects of local approaches include contact dermatitis with topical agents, prolonged wound drainage, and the burden of repeated application or later device removal. Importantly, the evidence base for local carriers in bone infection more broadly comes largely from non-diabetic chronic osteomyelitis, so extrapolation to the diabetic foot, where perfusion, neuropathy, and host factors differ, should be cautious.
Evidence From Randomized Trials
Two randomized trials are particularly informative. Ehya and colleagues (Journal of Diabetes Research, 2021) randomized 36 patients with neuropathic diabetic foot ulcers complicated by osteomyelitis to antibiotic-loaded bone cement or conventional vacuum-sealing drainage and followed them for 12 months. The cement group had significantly greater pathogen eradication, lower pain scores, shorter hospital stays and lower costs, faster wound-area reduction and healing, and fewer complications and infection recurrences. The trial was small and single-centre, and the comparator was a wound-care strategy rather than another antibiotic approach, which limits generalizability.
More recently, the BIG D-FOOT trial (Diabetes, Obesity and Metabolism, 2025) randomized patients with Texas grade 3 diabetic foot ulcers and osteomyelitis undergoing surgery to antibiotic-impregnated absorbable calcium sulfate granules (tobramycin or vancomycin) or placebo granules in a double-blind design. The primary outcome was post-surgical infective complications at 12 weeks. The study enrolled 20 patients and was stopped early after interim analysis; no infections occurred in the antibiotic group, while all post-surgical infections occurred in the placebo group (p = 0.010). These are encouraging findings from a rigorous design, but a very small sample and early termination can overestimate treatment effects, and larger confirmatory trials are needed before the result can be considered definitive.
What Guidelines Say
Current IWGDF/IDSA guidance on diabetic foot infection emphasizes bone sampling when feasible, surgical resection of infected or necrotic bone when indicated, appropriate and time-limited systemic antibiotics, and assessment and correction of limb ischemia (Senneville et al., IWGDF/IDSA guideline, 2023). The guidelines do not recommend routine use of topical antimicrobials in diabetic foot infection, and they treat local carriers as an area where higher-quality evidence is still being gathered. Practical questions that remain open include which patients benefit most, which antibiotic and carrier combinations are optimal, whether local therapy can shorten systemic antibiotic courses, and the long-term effects on amputation and recurrence.
Key Takeaways
Local antibiotic delivery is a biologically plausible adjunct to surgery for diabetic foot osteomyelitis, and early randomized data, including a small placebo-controlled trial of absorbable calcium sulfate, suggest it may reduce post-surgical infection. However, the overall evidence is limited by small sample sizes, heterogeneous designs, frequent reliance on retrospective data, and short follow-up. Surgical debridement, culture-guided systemic antibiotics, vascular assessment, and offloading remain the foundation of care. Larger multicentre trials with standardized outcomes such as remission, recurrence, and amputation are needed to define the role of local antibiotics.
References
- Field BCT, et al. The BIG D-FOOT randomized, double-blinded, controlled trial of bio-absorbable antibiotic delivery in calcium sulphate granules for the treatment of diabetic foot osteomyelitis. Diabetes, Obesity and Metabolism. 2025;27(7):4029.
- Ehya REM, Zhang H, Qi B, Yu A. Application and clinical effectiveness of antibiotic-loaded bone cement to promote soft tissue granulation in the treatment of neuropathic diabetic foot ulcers complicated by osteomyelitis: a randomized controlled trial. Journal of Diabetes Research. 2021.
- Soldevila-Boixader L, Pérez Fernández A, Muñoz Laguna J, Uçkay I. Local antibiotics in the treatment of diabetic foot infections: a narrative review. Antibiotics (Basel). 2023;12(1):124.
- Senneville É, Albalawi Z, van Asten SA, et al. IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections. Clinical Infectious Diseases / Diabetes/Metabolism Research and Reviews. 2023.
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