Application of Gentamicin-Impregnated Polymethyl Methacrylate Beads in the Treatment of Septic Arthritis and Osteomyelitis in a Green Sea Turtle (Chelonia mydas)
A three-year-old 8.2 kg female green sea turtle (Chelonia mydas) was referred to the Veterinary Medical Teaching Hospital, University
of Florida for evaluation of chronic bilateral polyarthritis of the front flippers. Five weeks prior to presentation, radiographic evaluation of the right
forelimb detected an abnormality at the elbow joint. Cultures of blood and joint fluid were positive for a gram-negative organism. The turtle was treated by the
referring facility with amikacin (5 mg/kg i.m. initial dose, then 2.5 mg/kg i.m. q 72 hr x 10 day), enrofloxacin (5 mg/kg i.m. q 48 hr x 10 day), cefotaxime (20
mg/kg i.m. s.i.d. x 10 day), and penicillin G procaine (10,000 IU/kg s.i.d. x 5 day, then q 48 hr), with no significant improvement in clinical signs. Upon
presentation, physical examination confirmed enlargement of the joints in both front flippers with impairment of function. Hematologic parameters were within
normal range and serum chemistries displayed hyperproteinemia (8.0 mg/dl) and hyperuricacidemia (12.2 mg/dl). Radiographs revealed multiple areas of bony lysis in
the proximal aspect of both humeri. Lesions were most severe on the right side, with bony lysis observed within the right scapula adjacent to the shoulder joint,
distal aspect of the right humerus at the level of the elbow joint, and radiolucency, irregularity, and bony lysis identified within the second carpal bone and
second carpometacarpal joint. Histopathology and culture of bone biopsies obtained from both humeri identified chronic severe osteomyelitis due to Serratia
marcescens. Blood cultures were negative for growth at two and five days. Parenteral therapy with amikacin (Amiglyde-V, 250 mg/ml, Fort Dodge Laboratories,
Fort Dodge, Iowa, USA) (5 mg/kg i.m. initial dose, then 2.5 mg/kg i.m. q 72 hr) was initiated based upon the susceptibility pattern.
The chronic nature of the lesion and results of diagnostic testing warranted surgical intervention for removal of infected material combined
with localized antibiotic therapy using antibiotic-impregnated polymethyl methacrylate beads. At surgery, a thick fibrous capsule containing caseous necrotic
material was identified and removed from the left and right scapulohumeral joint and right elbow joint. Following removal of infected material,
gentamicin-impregnated polymethyl methacrylate beads strung on surgical wire were implanted into the defect. Blood samples were collected from the occipital sinus
every 24 hr for 16 days following surgery for evaluation of systemic gentamicin levels.
Radiographic evaluation performed three weeks postoperative demonstrated no appreciable change in the previously identified lytic lesions.
Additionally, bony lysis was observed in both acetabula and femoral heads with poorly defined sclerosis of adjacent pelvic bone. Bilateral coxofemoral luxation
was also present. Appetite and behavior had begun to deteriorate and the turtle showed little ability to use the front flippers effectively. Due to the appearance
of additional sites of septic arthritis and poor prognosis for recovery, the turtle was euthanized. Postmortem findings confirmed Serratia marcescens as
the causative agent of the septic arthritis. Additionally, a large granuloma containing gram-negative rods was identified within the cerebrum. Fluid was obtained
postmortem from implanted joints for evaluation of local gentamicin levels.
In domestic species, osteomyelitis results from infection of bone through exogenous contamination or hematogenous exposure. Potentiating
factors in the pathogenesis of osteomyelitis include massive contamination, tissue ischemia, foreign material, highly virulent pathogens, and suboptimal immune
function. Because there was no history of previous surgical intervention or trauma in this patient, primary infection and spread was assumed to occur through
hematogenous exposure. Although negative results were obtained on blood culture, bacteremia associated with osteomyelitis is intermittent and antibiotic therapy
administered prior to referral may have inhibited (without eliminating) other foci of bacterial infections. Treatment of chronic osteomyelitis is difficult and
prolonged and, in cases where a definitive source of infection cannot be identified, prognosis is guarded.
The rationale for application of antibiotic impregnated polymethyl methacrylate beads (AIPMMA) is to provide locally therapeutic
concentrations of antibiotics. Because there is little systemic absorption of drug, the potential for toxic reactions is decreased. This technique is particularly
useful against infections localized in tissues with poor drug penetration, in situations where long-term or systemic use of antibiotics is contraindicated, or
with intractable or dangerous patients. AIPMMA beads are made using commercially available polymethyl methacrylate (PMMA) compounds (Surgical Simplex, Howmedica,
Rutherford, NJ, or Bone Cement, Zimmer, Charlotte, NC). Antibiotics are mixed thoroughly with the copolymer powder prior to the addition of the liquid monomer.
Antibiotics chosen should be bactericidal, effective against the pathogen of interest, therapeutic at low concentrations, water soluble, and demonstrate low
tissue toxicity. Because the polymerization reaction is exothermic, antibiotics used must also be heat stable up to 100°C. In this clinical case, gentamicin
was chosen based upon its low economic investment, effectiveness at low concentrations, water solubility, heat stability, and susceptibility of the bacterial
Gentamicin levels in serum and joint fluid were assayed using a fluorescence polarization immunoassay (Texas A&M University, College
Station, TX, USA) with a detection limit of 0.8 μg/ml. Serum gentamicin levels were 1.21 μg/ml at 24 hr following surgery and dropped below detectable
limits by five days postoperatively. Gentamicin levels in joint fluid were elevated above serum levels at 30 day post-implantation. In humans, the risk for
gentamicin-associated nephrotoxicity is increased when peak serum levels are maintained above 12-14 μg/ml, and trough serum concentrations are greater than
2.0 μg/ml. This data supports the use of AIPMMA beads to provide locally therapeutic drug concentrations with low systemic absorption of a potentially