Use of Highly Purified Synthetic Calcium Sulfate Impregnated With Antibiotics for the Management of Diabetic Foot Ulcers Complicated by Osteomyelitis

Diabetic foot osteomyelitis can be managed medically with systemic antibiotics alone or surgically by removing infected bone (1,2). Localized delivery of antibiotics directly to the bone offers a way to achieve an optimal concentration of chosen antibiotics at the site of infection. Antibiotics have been delivered directly into wounds using various vehicles, such as methyl methacrylate and absorbable antibiotic-impregnated gauze, in other clinical settings (3). Highly purified synthetic (HPS) calcium sulfate–based antibiotic therapy offers advantages of being biodegradable, having predictable elution characteristics to deliver antibiotics in concentrations far exceeding the minimum inhibitory concentration of the infecting organism, and having an ability to fill dead space (4,5). We report our experience of using HPS calcium sulfate impregnated with vancomycin and gentamicin in the management of osteomyelitis in the diabetic forefoot.

Over 18 months, 20 patients (15 males) with diabetic foot ulcers attending our multidisciplinary foot clinic were treated with minimal surgical intervention and local delivery of vancomycin and gentamicin using HPS calcium sulfate. The median age was 59 years (range 25–74). Mean HbA_1c was 8.4% (68 mmol/mol) (range 6.5–11% [48–97 mmol/mol]). All patients had forefoot ulcers with underlying osteomyelitis (all confirmed radiologically and 11 had earlier bone samples confirming osteomyelitis) and had failed to respond to regular wound debridement, systemic antibiotics, and off-loading. Eighteen patients had no evidence of peripheral vascular disease. Median ulcer duration prior to intervention was 11.5 weeks (range 3.6–104). Vancomycin and gentamicin were selected as the antibiotics of choice based on in vitro sensitivities of isolates obtained from diabetic foot infections in our laboratory. All surgical procedures were carried out by the same individual. HPS calcium sulfate powder was mixed with 1 g of vancomycin hydrochloride and 80 mg of gentamicin sulfate to form pellets. Sequestrae were excised, the bone was fenestrated and packed with the pellets, and primary closure was carried out. The ulcer was defined as fully healed when epithelization was complete and the intervention was considered successful when there was no reoccurrence for 12 months.

Intraoperative bone samples showed all the gram-positive isolates were sensitive to vancomycin. All but two gram-negative isolates were sensitive to gentamicin. Two patients grew Candida species in addition to their bacterial isolate and received an oral antifungal agent postoperatively. The need for postoperative antibiotics was decided individually as per clinical assessment and the median duration was 2 weeks (range 0–9). All patients achieved healing with a median time span of 5 weeks and no recurrence within 12 months after intervention (Fig. 1).

We have found this technique to be safe and effective for the treatment of forefoot diabetic osteomyelitis and believe that this has prevented more radical surgery. No adverse reactions were noted in these patients or indeed in any of our additional patients over the past 36 months. We now also offer this treatment to patients with midfoot and calcaneal osteomyelitis.

We acknowledge limitations of our case series given the small number of patients and suggest a randomized controlled trial to further evaluate this technique.