Vertebral Osteomyelitis In A Bottlenose Dolphin (Tursiops Truncatus): A Novel Treatment Using Sustained Release, Antibiotic Impregnated, Biodegradable Microspheres
Abstract
A previously beach stranded, juvenile, male, bottlenose dolphin (Tursiops truncatus) was diagnosed
with vertebral body osteomyelitis in June of 1999. Initial survey radiographs and later Computerized Tomography (CT) scans showed
a slab fracture involving nearly 1/3rd of the caudal vertebra at the leading edge of the flukes with evidence of
devascularization. Due to the nature of the lesion and the anticipated difficulties in healing at that site, we decided that
surgery was not a viable option and that long-term medical management would be necessary.
Multiple attempts to isolate an etiologic agent were unsuccessful but the animal tested positive for
Brucella (card, bapa, rivanol and ELISA tests). Initially systemic antibiotics were used to help control the presumed
infection, but this form of therapy was not considered a desirable long-term option despite the positive effects of decreasing the
neutrophilia and swelling associated with the condition. Intralesional injections were also used but the requirement for frequent
injections in a very small area raised concerns that our treatments would eventually result in significant local tissue damage.
Our goal was to maintain long-term efficacious levels of antibiotics at the site of the lesion while avoiding
any systemic effects of long term antibiotic administration. Various sustained release vehicles were investigated including
polymethylmethacrylate (PMMA), hydroxyapatite cement (HAC), polymer gels, and microspheres. Polylactide microspheres had the
desirable characteristics of being injectable, biodegradable, and providing prolonged sustained release of the antibiotics with
which they were impregnated.
The polylactide microspheres were impregnated with doxycycline and injected intralesionally. Serum levels of
doxycycline were monitored to assess the elution kinetics in vivo. An in vitro assay examining the elution of drug
into phosphate buffered saline was conducted in parallel with the serum assay in an attempt to simulate and monitor the
concentration of doxycycline in the region of the lesion.
An initial rise in neutrophils peaked within 2 days post injection and was presumably due in part to injection
site trauma. Following this peak the WBC profile improved but at ten days post-injection began to rise again. After several weeks
of rising neutrophils we decided to revert to systemic antibiotics. Oral doxycycline (2 mg/kg b.i.d.) was administered for ten
days but failed to check the increasing neutrophilia. Treatment was changed to amoxicillin/clavulanic acid (20 mg/kg b.i.d.). A
follow-up blood draw 4 days later indicated that total WBC and neutrophils were decreasing and were within normal limits the next
week. Since doxycycline was ineffective at the systemic level it was probably an inappropriate choice for local therapy. The
delivery system, however, is promising and we are evaluating other possible antimicrobials to pair with the polylactide
microspheres. In the meantime the dolphin is being maintained on amoxicillin/clavulanic acid and bloodwork is being monitored on a
weekly basis.