NATIONAL HARBOR, MD – Local delivery of an antibiotic using impregnated bone-cement beads enabled sterile cultures to be achieved in the majority of infected surgical sites before final repair or graft replacement, according to a small, retrospective study reported by Dr. Dennis F. Bandyk.
This type of nonbiodegradable antibiotic implant is especially useful in cases of infection related to a groin incision, he said at the annual meeting of the Eastern Vascular Society.
"You can make these drug-delivery beads in the operating room in about 10 to 15 minutes.
"After EVAR [endovascular aneurysm repair], we have about a 5% incidence of surgical site infection. Arterial revascularization in the literature has a 10% to 30% infection rate, [and] it’s 18% in lengthy lower limb revascularization at our institution in Tampa. Major amputations generally range from a 15% to 25% infection rate, with 22% for the last 3 years at Tampa. The problem likely exists because of colonization with staph, particularly MRSA [methicillin-resistant Staphylococcus aureus], of injured and ischemic tissue, especially with involvement of the groin," Dr. Bandyk said.
"We have no decent methods of preventing these sorts of surgical site infections," he noted. The approach that his group takes to treat these infections is to use sequential in situ antibiotic treatment.
"I believe that many of the SSIs [surgical site infections] we have follow this theme of a biofilm-mediated infection," he said. Specific pathogenic strains colonize the area; they produce an extracellular matrix that then creates selective antibiotic resistance, since many of the antibiotics don’t penetrate biofilms.
The reported study comprised a 7-year case audit of 78 patients (55% male) who had complex SSI following peripheral arterial repair, treatment of an infected hip, or above- or below-knee lower limb amputation (12 infected stumps).
Antibiotic delivery directly to the wounds was mediated via the use of polymethyl methacrylate (PMMA) bone-cement beads. For gram-positive infection, which occurred in 70% of patients, the beads were impregnated with vancomycin (2 g/40 g PMMA) in the early part of the case series. Daptomycin (1.5 g/40 g PMMA) was found superior to vancomycin during in vitro testing, and became the antibiotic of choice for patients seen later in the case series. Tobramycin (2 g/40 g PMMA) was used for gram-negative infection, seen in 30% of patients. This was coupled to culture-specific parenteral antibiotics for 3-6 weeks. MRSA accounted for at least half of all early and late infections, and thus MRSA must be taken into account when comparing therapy options.
Infected surgical sites were explored and cultured, and based on a Gram stain of pus or a prior culture result, PMMA antibiotic-impregnated beads were implanted into the wound after soft tissue debridement, including the adjunct use of wound irrigants such as the "brown volcano" – a mixture of salt, peroxide, and Betadine – which disrupts biofilms.
Arterial infections underwent an average of 2.3 debridements. Surgical wounds were primarily closed with a planned bead exchange 3-5 days later (often repeated one to three times) to confirm sterilization prior to graft preservation or in situ graft replacement. The main outcomes were rates of wound sterilization (negative culture) based on wound type, procedures for persistent infection, and freedom from arterial repair infection.
In terms of outcomes, there were no cases of limb loss, higher-level amputation, or death at 30 days. The rate of recurrent infection was 7% over a mean follow-up period of 3 years. Sterile wound cultures were achieved in 91% of cases after 1-3 bead exchanges. Daptomycin beads appeared to work the most rapidly, Dr. Bandyk added.
"So you can sterilize the wound with the prosthetic in place," he noted.
Because of this strategy’s success, his group has transitioned to treating almost 58% of their SSIs in this way, said Dr. Bandyk, professor of surgery at the University of South Florida, Tampa.
"You can make these drug-delivery beads in the operating room in about 10 to 15 minutes. Vancomycin is bacteriostatic and does not penetrate biofilms; daptomycin is a bacteriocidal antibiotic that does penetrate biofilms," he explained.
In addition, because the use of antibiotic beads in general "isn’t anything new, you get paid for putting it in and paid for pulling it out."
Discussion after the presentation focused on the expense of daptomycin versus vancomycin and the difficulty of obtaining it in many institutions due to cost and issues of antibiotic stewardship. Dr. Bandyk responded, "I thought we were surgeons. Most surgeons believe that we should use a bactericidal agent that can get to the tissue with a chance of killing the bacteria that are there. I didn’t realize that we were in this sort of price war with the hospital. If you look at what a biofilm infection is, you will understand why vancomycin doesn’t work."