The formation of biofilm is one of the main contributing factors for unsuccessful treatment of osteomyelitis. It is formed through the bacterial adhesion to the fragments of dead bone. Poor perfusion or devascularization of an infected bone with changes in local pH further limits the diffusion of parental antibiotics.
Calcium sulphate, a biocompatible and completely reabsorbable local carrier for antibiotics, has shown promising results in treating osteomyelitis. It is associated with less systemic effect and compliance issues when compared with conventional treatment of surgical debridement and prolonged systemic antibiotics.
Keywords: Calcium Sulphate; Ilizarov frame; Osteomyelitis; Staphylococcus aureus
Despite gradual advances in surgical techniques and antimicrobial agents, the treatment of osteomyelitis remains a challenge. Its management is often difficult as it requires extensive surgical debridement and prolonged antibiotics therapy [1,2]. However, the relapse rate remains high; the primary contributing factor is the formation of a bacterial biofilm. Systemic antibiotics have poor penetration and often require three to four fold increase in concentration to achieve bactericidal activities . Long-term systemic antibacterial therapy can become problematic due to compliance, drug toxicity and dead-space formation.
To counter these problems, systems that release antibiotics locally have been created. Stimulan (Biocomposities Ltd, Keele, UK) is a biodegradable synthetic calcium sulfate, w h i c h is completely absorbed and replaced by new bone. Biodegradable and absorbable carriers offer the advantage of avoiding the need for a second removal operation. Synthetic calcium sulfate with 100% purity was first introduced in 2000. This avoids potential toxicity associated with impurities in natural mineral sources of calcium sulfate .
A 71-year-old man was referred to us with persistent osteomyelitis of his distal tibia fracture following an internal fixation in August 2013 (Figures 1 and 2). He was treated with an above knee backslab and sent home by emergency department after being diagnosed with closed injury to his right distal tibia and fibula fracture. His medical history included hypertension and a previous history of deep vein thrombosis, whi ch had been treated with Warfarin. When he presented to fracture clinic ten days later, he had developed pressure ulcers over his left heel and medial malleolus.
Orthopaedic surgeons at the referring hospital decided to treat with an external fixator to allow soft tissue healing before definitive surgery. After three weeks of external fixation, the wound over his right medial malleolus had healed. Open reduction and internal fixation of his right tibia fracture was performed in September 2013 (Figures 3 and 4).
Seven weeks later, skin over the medial malleolus broke down again and left the distal part of tibial plate exposed (Figure 5). His tibia fracture failed to heal secondary to osteomyelitis.
Microbacterial culture from superficial wound swab grew MRSA. Intra-operative bone and deep tissue samples showed MRSA, enterococcus and E. coli. All isolates were sensitive to the combination of teicoplanin and gentamicin. Computed Tomography (CT) angiogram confirmed patient lower limb circulation.
At referring hospital, he received eight weeks of intravenous teicoplanin and gentamicin with standard MRSA eradication therapy. Throughout the duration of his intravenous antibiotics, he stayed isolated in a side room. However, this failed to resolve his osteomyelitis and pressure ulcer over the medial malleolus. He was given the option of an above knee amputation, and referred to a foot and ankle specialist at University Hospital South Manchester for a second opinion with plastic surgery input.
In May 2014, his tibia non-union secondary to osteomyelitis was stabilised with Ilizarov frame. Calcium sulfate beads containing gentamicin were applied to the fracture site and the medial malleolus (Figures 6 and 7). Internal fixation was removed during operation. Vacuum therapy was applied over the medial malleolus. Patient had two days of intravenous teicoplanin post-operatively before discharging home.
In theatre environment, Stimulan powder mixes easily and quickly with gentamicin liquid so there is no soaking required. This reduces unnecessary use of precious theatre time during mixing. Calcium sulfate from Stimulan kit can be modified in three sizes of bead (3 mm, 4.8 mm or 6 mm) or as a paste for injection to provide flexibility depending on the size of the defect. In this case, we applied 4.8 mm calcium sulfate beads at both the fracture site and the medial malleolus.
Outcome and follow-up
At six weeks follow-up, most of the calcium sulfate beads were absorbed, which was shown radiologically (Figures 8 and 9).
Three months postoperatively, CT scan of lower leg demonstrated callus formation and fracture union (Figures 10 and 11). Further magnetic resonance imaging showed no signs of osteomyelitis.
Tissue viability nurses followed his pressure ulcers. The wound over the medial malleolus healed three weeks after the operation (Figure 12). The heel pressure ulcer was treated with dressings impregnated with surgihoney.
In an attempt to overcome the issues related to the treatment of osteomyelitis, systems of local antibiotic release have been developed. One of the most commonly used materials is polymethylmethacrylate (PMMA) . It is not biodegradable therefore a second operation is required for it to be removed once antibiotic the is released. If it is left in place, it will prevent bone ingrowth  and become a potential space for future infection .
Over the last two decades, several biodegradable and absorbable carriers such as polylactic acid, hydroxyapatite, calcium phosphate and collagen materials have been developed . The advantages of calcium sulfate include its biodegradability, predicable elution properties, osteconductivity, and ability to fill dead space . Recent studies have shown that osteoblasts attach to and absorb calcium sulfate . It provides an osteoconductive environment for vascular ingrowth. Calcium sulfate has the potential to release effective local antibiotic concentrations for a period of at least forty-two days without affecting the chemical nature and antimicrobial efficacy . Results in vitro have revealed that Stimulan admixed with 10% moxifloxacin was very effective in achieving complete eradication of the causative pathogen in an experimental model of osteomyelitis caused by MRSA [12,13].
Calcium sulfate as a carrier is a new treatment option for osteomyelitis associated with internal fixation. In our experience it has less systemic effects, releases more effective antibiotic concentrations locally, reduces the length of parenteral antibiotic use and reduces the length of inpatient stay.