Diabetic Foot Ulcers and Osteomyelitis: Use of Biodegradable Calcium Sulfate Beads Impregnated With Antibiotics for Treatment of Multidrug-Resistant Organisms

Prashant Patil, MCh, FDFS; Rajeev Singh, MS; Apurva Agarwal, MS; Rajiv Wadhwa, MS; Aran Bal, MS, PhD; Sanjay Vaidya, MS, MCh


Wounds. 2021;33(3):70-76. 

In This Article

Abstract and Introduction


Introduction: Treatment of diabetic foot infection generally involves prolonged antibiotic therapy, surgical debridement or amputation when indicated, and management of the patient's comorbidities. Systemic antibiotics are often prescribed when an ulcer is showing clinical signs of infection; however, treatment using systemic antibiotics alone may yield poor results. In the diabetic foot, local delivery systems have been explored to minimize systemic toxicity and eliminate concerns about antibiotic penetration while also achieving high local doses of antibiotics.

Objective: This case series evaluated the clinical outcomes of a commercially pure, synthetic, antibiotic-loaded calcium sulfate for the management of diabetic foot ulcers (DFUs) complicated by osteomyelitis.

Materials and Methods: A total of 106 patients requiring either major or minor debridement, amputation of 1 or more toes, forefoot amputation, or below-knee amputation received calcium sulfate combined with combinations of meropenem, colistin, or vancomycin based on antibiotic susceptibility from microbiological cultures.

Results: Calcium sulfate beads were mixed with meropenem in 64 cases, colistin in 35 cases, and vancomycin in 7 cases. At final follow-up, 98 of the 106 patients (92%) had no recurrence of infection (mean follow-up, 10 weeks [range, 6–16 weeks]). No systemic adverse reactions to the local delivery of antibiotics were observed in this study.

Conclusions: The use of locally released antibiotics from synthetic recrystallized calcium sulfate may offer significant benefits in the management of DFU infection compromised by poor circulation, polymicrobial growth, and associated renal and cardiac comorbidities.


Diabetes is a life-impacting condition that can be characterized by the presence of persistent hyperglycemia. Additional microvascular and macrovascular complications, such as cardiovascular disease, retinopathy, nephropathy, neuropathy, and impaired wound healing, have also been associated with the disease. The macrovascular complications (eg, stroke, heart disease) are not specific to diabetes; however, the risk of cardiovascular disease increases up to 8-fold in people with diabetes or impaired glucose tolerance.[1]

Prolonged exposure to hyperglycemia plays an important role in the development of type 2 diabetes. Over time, glucose reacts with several different macromolecules, including proteins, lipoproteins, and nucleic acids to form irreversible advanced glycation end products that can modify both extracellular matrix and plasma proteins. This can lead to a number of complications, including foot ulceration, peripheral arterial disease, and peripheral neuropathy. Foot ulcers are common in patients with diabetes, with a reported prevalence as high as 25%.[2,3] The ulcers are frequently complicated by infection, which regularly results in increased patient morbidity and mortality as well as treatment costs. As a result of infection, these patients are often readmitted to hospital owing to several complications, which can ultimately lead to higher level amputation.[4] Up to 25% of all hospital admission days for patients with diabetes mellitus in the United States are related to foot complications as a result of infection.[5]

Treatment of diabetic foot infection (DFI) generally involves prolonged antibiotics, surgical debridement, or amputation as well as management of the patient's comorbidities. Given that infection is frequently the reason for lower limb amputation, infection control is important in preventing amputation and promoting healing.[6] Systemic antibiotics are often prescribed when an ulcer is showing clinical signs of infection;[6,7] however, resolution of infection after treatment of DFI with systemic antibiotics varies widely, with reported rates of clearance of infection between 5.6% and 77.8%.[8]

Typically, systemic antibiotics are considered to have achieved sufficient concentrations if they reach the minimum inhibitory concentration (MIC) for the target bacteria.[9] However, it is widely acknowledged that bacteria form biofilms in most or all cases of soft tissue infection.[10] This is significant because biofilms have substantially increased tolerance to antibiotics, sometimes by a factor of 1000,[11] and therefore, the MIC is not a useful predictor of successful treatment.[12] In addition, antibiotic penetration to the distal areas of the foot can be difficult.[13]

Local delivery systems have been studied to minimize systemic toxicity and eliminate concerns about antibiotic penetration, while also achieving high local doses of antibiotics in the management of the diabetic foot.[14] For many years, antibiotic-loaded polymethyl methacrylate (PMMA) cement in the form of beads or spacers has been used in the treatment of foot and ankle infection.[15–18] A promising alternative to PMMA is calcium sulfate. Absorbable mineral-based bone cements such as calcium sulfate are not as mechanically strong as PMMA cements, but they provide some advantages for antibiotic delivery and infection control. Unlike PMMA, mineral-based cements do not require removal (because they are naturally absorbed) and, because there is little temperature increase during setting, they have the capacity to accommodate a wider range of heat-sensitive antibiotics. Evidence in the literature has shown improved antibiotic release from calcium sulfate relative to that of PMMA beads and, importantly, complete biodegradation of the calcium sulfate.[19–21]

Stimulan Rapid Cure (Biocomposites Ltd) is a pharmaceutical-grade calcium sulfate hemihydrate. It is manufactured using a synthetic process, which results in a material with 100% purity.[22,23] The material has a low set temperature, which aids in the mixing of heat-sensitive antibiotics. The biodegradable nature of the product eliminates the need for subsequent surgical removal, and previous work has indicated that it may be an effective tool in preventing the formation of biofilms.[11,24] The clinical use of antibiotic-loaded calcium sulfate has been shown to be safe and effective as a treatment for radiologically confirmed osteomyelitis, particularly in the management of diabetic foot ulcers (DFUs).[25,26]

The purpose of this study was to examine the use of commercially pure, synthetic, antibiotic-loaded, dissolvable calcium sulfate beads in treating 106 patients with DFI.