Antibiotic-Impregnated Plaster of Paris for Veterinary Use
by Barbara Forney, VMD
Basic Information
Calcium sulfate hemihydrate (CaSO4 2H20), commonly known as plaster of Paris or POP, may be used as a substitute for autologous bone-graft and as a means of delivering local antibiotic at the site of a potential or established bone-infection. Antibiotic-impregnated POP implants are used by trauma surgeons for prophylaxis in the initial treatment of open fractures and have been used successfully to treat bone defects in patients with chronic osteomyelitis. Thirty years of experience in human orthopedic surgery has demonstrated the value of antibiotic-impregnated POP beads and flakes.
Prospective Patients
The advantage of implantable systems for delivering antibiotics is their ability to deliver sustained local therapeutic drug-levels while minimizing the potential for systemic toxicity. The veterinary literature contains references to the use of antibiotic-impregnated POP in rabbits, raptors, dogs and horses.
The Role of Local Antibiotic Delivery in the Treatment of Osteomyelitis
Orthopedic infections present unique challenges due to local factors at the site of infection and survival strategies of bacteria. There are many features of orthopedic infections that may protect or shield bacteria from systemic antibiotics. These include wound pH, which is affected by bacterial infection; high levels of bacteria, which can decrease the effectiveness of antimicrobials; fibrinous exudates; bacterial biofilms; inflammation; thickened synovial membranes and orthopedic pathologies. Effective treatment of orthopedic infections may require localized antimicrobial levels at up to 100 times the systemic minimal inhibitory concentration (MIC). Because local antibiotic-therapy is able to produce these high levels at the site of infection with minimal systemic effect, local antibiotic-therapy is used increasingly as an adjunct to the traditional therapies. Traditional therapies would include debridement of infected, devitalized or necrotic tissue, systemic antibiotics and removal of infected hardware.
Other forms of local antibiotic-delivery used in orthopedic practice include regional intravenous-perfusion, intraosseous perfusion and joint lavage. In contaminated wounds without boney involvement, antibiotic irrigation has been shown to be more effective in eliminating local bacteria than antibiotic-impregnated implants.
Specific Characteristic of Antibiotic-Impregnated POP
POP is a reliable bone-void filler and bone-graft substitute. It is used commonly in human medicine to treat boney defects because it is both well-tolerated and absorbed by the body. POP is biocompatible, bioabsorbable, osteoconductive and easy to work with. The uniform size and shape of the CaSO4 crystals in medical-grade POP allow for slower and more- predictable solubility and resorption of the antibiotic-impregnated beads. POP beads normally dissolve in vivo within 30 to 60 days depending on volume and location. Antibiotic-impregnated POP also may be combined with demineralized bone matrix (DBM) because this combination is both osteoconductive and osteoinductive and it may further reduce healing time. Other materials that may be impregnated with antibiotics to treat bone and joint infections include polymethylmethacrylate (PMM) and other synthetic polymers, calcium hydroxyapatite, bioabsorbable sponge or collagen. The indications for PMM beads combined with antibiotic are slightly different because PMM is not absorbable and will need to be removed.
Elution Characteristics
In uncoated POP beads impregnated with gentamicin there is an initial burst release of antibiotic in the first 48 hours. Eighty percent of the antibiotic is released in the initial burst. Therapeutic levels of aminoglycosides were eluted from POP beads for 14 to 21 days in two different in vitro studies. Initial antibiotic release from POP is four times higher than the burst release from similar PMMA pellets. This led the authors of one study to conclude that POP beads might be particularly suitable in infection prophylaxis in open fractures. Coating of the POP beads with a variety of substances including poly lactide-co-glycolide or porcine small-intestinal submucosa will decrease the initial burst and prolong the elution curve.
Antibiotic Choices
In in vitro testing, aminoglycoside antibiotics (gentamicin, tobramycin, amikacin and vancomycin) and metronidazole have been shown to remain stable in POP beads incubated at 37c for 14 days. Penicillins and cephalosporins were unstable under these experimental conditions and had leached from the POP beads in 48 hours. Quinolones, glycopeptides and sodium fusidate had 40% diminished bactericidal activity and the quinolone beads were too brittle for practical use.
Dosing
Experimental work done in animal models using 10% tobramycin POP pellets has led to a recommendation that the total dose in the antibiotic POP implants be no more than the normal 24-hour intravenous dose. In these experiments, serum levels of tobramycin were elevated for one day (burst effect) and the local levels remained elevated for 14 to 28 days. No adverse effects were seen on clinical pathology or on post-mortem examination.
About the Author
Dr. Barbara Forney is a veterinary practitioner in Chester County, Pennsylvania. She has a master's degree in animal science from the University of Delaware and graduated from the University of Pennsylvania School of Veterinary Medicine in 1982.
She began to develop her interest in client education and medical writing 1997. Recent publications include portions of The Pill Book Guide to Medication for Your Dog and Cat, and most recently Understanding Equine Medications published by the Bloodhorse.
Dr. Forney is an FEI veterinarian and an active member of the AAEP, AVMA, and AMWA.
You can purchase books by Dr. Forney at www.exclusivelyequine.com
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