Topical Resorbable Antibiotic Cement and Synthetic Extracellular Matrix Dressings in a Complex Clinical Case
Clinicians can deliver antibiotics to infection sites via intravenous, intramuscular, or oral administration, but penetration becomes challenging when perfusion is poor. Poly(methyl methacrylate) (PMMA) is a commonly used cement that one can mix with antibiotics to deliver antibiotic therapy directly to an infected site, bypassing the need for vascular transport. The use of PMMA bone cement has disadvantages, however, which include methyl methacrylate (MMA) release and high exothermic temperature during the PMMA polymerization, which can cause thermal necrosis. PMMA it is not resorbable and therefore requires a second surgery for removal, and it can become a nidus for infection if colonized by bacteria.1-4 Certain bone cements, such as calcium sulfate, have the advantage of complete resorbability, and therefore do not require additional surgery to remove and do not act a nidus for infection.3 Surgeons can load a wide range of antibiotics into antibiotic cement depending on the target organism, including vancomycin and gentamycin.1
In the case presented below, our approach to a complex infection case involved 2 unique tools. First was an absorbable bone cement (STIMULAN® Rapid Cure, Biocomposites®) manufactured from medical grade calcium sulfate intended for use as a bone void filler for voids or gaps not intrinsic to the stability of the bony structure.3 It is engineered through a multistep, six-233k DRy26™ recrystallization method.5 It contains no hydroxyapatite, PMMA, or insoluble impurities, and is completely absorbable.3, 6-11 It has been demonstrated to not act as a nidus for infection.3,11
The wound matrix we used (Anthem™, Renovoderm) provided a microporous scaffold for cellular migration, infiltration, and regenerative cell proliferation.12-13 It is composed of naturally degrading polyglycolic acid and Poly(L-Lactide-co-caprolactone) which then provides sustained release of glycolic, caproic, and lactic acids into the wound microbiome. This creates an inhospitable environment for bacteria by lowering the pH of the wound. Lowering the pH of a wound can decrease microbial infection rates, bacterial virulence, and biofilm formation.13-21
Based on our experience with this case, we propose that, when used in combination therapy, synthetic extracellular matrix dressings and antibiotic-loaded resorbable bone cement can complement each other and work synergistically to eradicate infection and promote wound healing.
Case Report
We present the case of a 73-year-old male with a past medical history of type 2 diabetes mellitus, peripheral neuropathy, and peripheral vascular disease. The patient had undergone a right lower extremity angiogram with posterior tibial artery angioplasty in August 2022 and right transmetatarsal amputation secondary to right foot ulcerations with osteomyelitis in June 2023. In February 2024 the patient developed an ulceration of the left hallux which progressed to osteomyelitis and ischemic changes of the left forefoot began to occur. In March 2024 the patient had a left lower extremity angiogram with peroneal artery angioplasty. Unfortunately, the patient’s ulceration, infection, and ischemic changes continued to worsen, resulting in a left transmetatarsal amputation in May 2024 by a community surgeon. The patient was lost to follow up with the community surgeon and returned to our care in July 2024, 8 weeks postoperatively, fully dehisced and grossly infected.
At that time, we conducted a thorough history, complete review of systems, and a focused lower extremity examination. Of note, he had no known drug allergies and was on long-term anticoagulation therapy. He did not have a history of tobacco use. Physical exam demonstrated absent pedal pulses, diminished protective sensation, and no gross deformity of the foot or lower extremity except for bilateral transmetatarsal amputations. The posterior tibial artery pulse was monophasic on Doppler exam and we were unable to detect the dorsalis pedis artery pulse at that time.
The dehisced left transmetatarsal amputation incision site measured 15.0cm x 2.5cm x 1.2cm with visible exposed fourth and fifth metatarsal shaft remnants. The patient reported intense pain from the incision site. The incision flaps appeared poorly perfused. The periwound skin was erythematous and fragile, with malodorous and sanguinopurulent drainage noted from the wound. The left lower leg and foot were edematous. The wound bed was comprised of 40% granular, 50% fibrotic, and 10% necrotic tissue.
Radiographs demonstrated possible osteomyelitis of the fifth metatarsal but did not reveal soft tissue emphysema or other emergently concerning findings. Glycosylated hemoglobin was 7.8%. Wound swab culture showed methicillin-resistant Staphylococcus aureus (MRSA). We prescribed oral antibiotic therapy, doxycycline, which continued throughout the duration of treatment (Figure 1).
Details on the Initial Intervention
At the initial visit, which took place in our outpatient podiatry clinic, after an informed consent discussion, we performed a debridement of the left amputation site. Local anesthesia took place via an ankle block and we performed a full sterile scrub and prep for sharp debridement of all nonviable tissue, down to and including bone. Using bone cutters and sterile technique, we resected the distal remnants of the metatarsal shafts, passed them from the surgical field, and sent them for surgical pathology and culture/sensitivity testing. Hemostasis was achieved with resorbable oxidized cellulose and we applied chlorhexidine to the periwound skin and allowed it to air-dry. We then applied the aforementioned synthetic wound matrix directly to the wound bed after being cut to size and soaking in sterile saline (Figure 2). Resorbable antibiotic cement pellets mixed with gentamicin and vancomycin were then topically applied over top the synthetic wound matrix dressing (Figure 3). This was followed by application of benzoin tincture to the periwound skin to protect against wound drainage and help adhesives properly adhere. Coaptive film and a non-adherent dressing secured the synthetic extracellular matrix dressing and antibiotic-loaded resorbable cement pellets. Retention sutures assisted in reapproximating the incision flaps and for intended secondary healing (see Figure 3A). Dry, sterile, noncompressive outer dressings were employed. The patient’s left foot was offloaded with the Optima SBi Motus 2.0 boot (Optima Molliter). The bone segment testing confirmed MRSA osteomyelitis.
Understanding the Subsequent Treatments
We followed the below protocol at each of the subsequent seven visits that took place in our outpatient podiatry clinic, each spaced 2 weeks apart. We fully scrubbed and prepped the left lower leg and foot in a sterile fashion before flushing any remaining antibiotic pellets from the incision using sterile saline. We sharply debrided all nonviable tissue and recorded wound size measurements at each visit. No anesthesia was needed for the intervention due to the patient’s foot being insensate.
As previous, chlorhexidine and benzoin tincture were applied to the periwound skin by appropriate protocols. We then reapplied the synthetic wound matrix directly to the wound bed after cutting it to size and soaking it in sterile saline. This was followed by topical application of the resorbable antibiotic cement pellets mixed with gentamicin and vancomycin. We removed and replaced the previous retention sutures, progressively bringing the incision flaps closer together. The same securement, offloading, and dressings were implemented each time. Local signs of infection improved with each successive visit, as did the patient’s reported pain, and we noted signs of continued progressive wound healing.
At the ninth visit, the wound had fully healed with no residual signs of infection and no pain reported. The patient transitioned to regular shoe gear with a toe filler insert and resumed normal activity.
Considering the Impact of This Treatment Course
Fourteen weeks of combination therapy using antibiotic loaded resorbable bone cement and synthetic extracellular matrix arrested the active infection in this dehisced and poorly perfused transmetatarsal amputation site. Of note, the patient achieved restoration of functional use of the lower extremity, wound pain resolution, and complete closure of the transmetatarsal amputation site.
We feel that wound healing in this case was contributed to by a multitude of factors. First, the natural degradation of the components of the synthetic extracellular matrix dressing led to a decrease in pH within the wound bed. This, combined with local antibiotic delivery from the topically applied resorbable cement, prevented biofilm formation, worked towards eradicating the infection, and facilitated complete wound healing, when paired with debridement.
It is important to note that this case was performed at the Southern Arizona Veteran Affairs Health Care System; therefore, cost and reimbursement were not factors in determining treatment. One should be aware that Anthem Wound Matrix is branded specifically for the Department of Veteran Affairs. In private and commercial sectors, it is branded as Phoenix™ Wound Matrix (RenovoDerm).
Antibiotic-loaded resorbable cement pellets and synthetic extracellular matrices may be reimbursable through insurance and have their own designated HCPCS codes. However, the cost-to-benefit ratio would need to be assessed on an individual provider and patient basis. All pricing of the wound care products used in this case are available to the public through the Department of Veteran Affairs Federal Supply Schedule. Please consult your local LCDs or payer guidelines for policies that may apply to your region and practice.
In Conclusion
When presented with this case, our goals of therapy were to prevent a more proximal amputation, eradicate the infection, minimize patient discomfort, restore function of the limb, and achieve complete wound closure. The outcome of this case supports the potential of topical antibiotic-loaded resorbable bone cement for lower extremity infected wounds, particularly in the setting of poor perfusion,
in combination with synthetic extracellular
matrix dressings. The wound achieved completed closure after 14 weeks of combination therapy. Radiographs obtained at the end of therapeutic period demonstrated no new osseous erosions concerning for osteomyelitis and throughout the course of the therapy no new soft tissue infections occurred.
Disclosures
The authors of this article declare no conflict of interest. The companies involved had no role in the design of the study; in the collection, analyses, or interpretation of date; in the writing of the manuscript, or in the decision to publish the results.
Acknowledgements
This material is based upon work supported by the Department of Veterans Affairs, Veterans Health Administration, and Office of Research and Development. The authors gratefully acknowledge the Southern Arizona VA Health Care System which provided facilities and materials for this research.
Dr. Evensen, is a PGY-III resident and Chief Podiatry Resident in the Department of Veteran Affairs, Southern Arizona Veteran Affairs Healthcare System in Tucson.
Dr. Samoy is a Diplomate of the American Board of Podiatric Medicine and a podiatrist in the Department of Veteran Affairs, Southern Arizona Veteran Affairs Healthcare System in Tucson.
Dr. Jolley is a podiatrist in the Department of Veteran Affairs, Southern Arizona Veteran Affairs Healthcare System in Tucson.
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