Researcher uses collagen to deliver antibiotics
Technique is especially effective for foot ulcers
Impregnating collagen with commonly used antibiotics can help resolve infections in deep soft tissue wounds or osteomyelitis in the feet, according to one podiatrist. Lawrence Kollenberg, DPM, medical director of the Garland County Foot Clinic in Hot Springs, AK, reports the new technique in the electronic journal, World Wide Wounds.1
Eliminating serious infections of the foot is crucial for patients with diabetes because such infections often lead to amputation. Tissue concentration of antibiotics depends on the ability to deliver therapeutic concentrations to infected tissue for extended periods.
Kollenberg points out that in patients with infections, blood flow to infected areas is often compromised, therefore, delivery of macrophages and nutrients that enhance infection defenses is decreased. The same decrease holds true for antibiotics. He has developed a new drug delivery system for clinicians to use on their own patients, perhaps decreasing the number of amputations and shortening hospital stays.
Type I collagen is vehicle for delivery
Kollenberg’s technique relies on type I collagen as the drug delivery vehicle. Type I collagen is the most abundant form of collagen in humans. The substance is well-tolerated and completely biodegradable. According to Kollenberg, the substance has previously been used to deliver drugs for a number of applications:
• as a carrier in ocular applications;
• as a carrier for drugs such as tretinoin and lidocaine;
• transdermally to deliver calcium channel blockers and beta blockers;
• impregnated with gentamicin to treat chronic osteomyelitis.
Collagen, he adds, has also been shown to release drugs at a constant rate over several days.
Kollenberg used type I collagen to deliver sustained-released antimicrobial agents to patients with active foot infections involving deep soft tissue or bone. During the study, no patients were admitted to the hospital or given intravenous antibiotics during the course of care, though they had initially been treated with oral antibiotics. Home health agency nurses who were trained in the protocol administered the collagen-based antibiotics. Nurses monitored patient compliance for diabetes checks and antibiotic administration.
At the initial visit, infected areas were evaluated and a determination was made whether the infection had reached bone. "The physician should probe gently until resistance is met and then feel the tissue with the instrument. This minimizes trauma to surrounding tissue," says Kollenberg.
Tissue specimens were cultured. After surgical debridement, wounds were packed with type I bovine collagen mixed with gentamicin, then covered by a secondary sterile dressing. Kollenberg recommends packing the wound lightly because collagen expands when fluid is applied to it.
All 12 patients were initially treated with gentamicin impregnated into type I bovine collagen and were instructed to remain in bed or on a couch at home. All were treated with warm moist compresses from the knee to the ankle/mid-foot. This action was intended to keep the warm compress off the infected area and dressing. In addition, five patients were given cephalexin and clindamycin. No patients were hospitalized or received injection administration of antibiotics.
During the study period, patients visited the clinic at least twice during the first week of treatment and then weekly until the infection was resolved and wounds were closed. If bacterial organisms were determined to be resistant to gentamicin or the oral agent, then antibiotics were changed.
Patients or home health nurses were given detailed instructions on dressing application. Gauze was used to cover the affected area to prevent the film dressing from rolling or sticking to clothing. Dressings were changed daily.
All patients initially started on gentamicin in type I collagen. Six remained on gentamicin until their infections resolved and wounds were 100% re-epithelialized. The remaining six patients demonstrated resistance to gentamicin; three of them were switched to clindamycin and three were started on vancomycin impregnated into type I bovine collagen. All oral antibiotic agents were discontinued after three weeks. Patient resolution to complete healing ranged from 35 to 162 days.
Patients were followed until the infection process had been resolved for 30 days. Long-term care included prophylactic surgery to improve biomechanical forces or the use of biomechanically correct orthotics. After the initial infections were brought under control, patients received specially modified and padded surgical shoes to protect plantar or digital lesions. Patients were given the following instructions:
• Walk minimally.
• Wear special shoes at all times when out of bed.
• Apply warm, moist compress to hind foot and leg two hours on and two hours off while awake.
• Take sponge baths only.
• Continue regular or special diet.
• Start vitamins — multivitamins (Centrum) three times daily for 30 days, then vitamin C, 1 gram twice daily (until healed).
• Diabetic patients: Monitor fasting blood sugar in a.m. and p.m. unless otherwise directed by primary care physician.
• If fasting blood sugar >200 mg, call primary care physician.
• Take antibiotic on prescribed course.
• Change dressing once daily.
• Check oral temperature three times daily. Begin paracetamol (Tylenol) if oral temperature >38.5° C.
• Take pain pills as prescribed if needed.
• Do not follow advice of friends or other outside individuals before checking with clinic nurse first.
• Keep all follow-up appointments.
• Notify doctor if any red streaks appear on leg or if there is an increase in swelling of the foot, ankle, or leg.
• Keep collagen mixture away from moist areas, e.g., bathroom. Store in cabinet.
Kollenberg notes that his study shows a potential for "cost-effective outpatient care even when serious limb threatening infections are treated," but acknowledges that more work needs to be done before conclusions about safety, efficacy, and care can be made. "The numbers presented here are too small for any scientific conclusions to be drawn from this," he says.
He also says that in his study it was not possible to measure antibiotic levels in tissue. He cites previous research that showed minimal or no toxic drug absorbed by the blood stream.
Reference
1. Kollenberg L. A new topical antibiotic delivery system. World Wide Wounds (electronic wound journal). 1998. Surgical Materials Testing Laboratories, Bridgend, Wales, UK. http://www.smtl.co.uk/World-Wide-Wounds/.
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