Prevention and treatment of experimental osteomyelitis in dogs with ciprofloxacin‐loaded crosslinked high amylose starch implants

Abstract

Crosslinked high amylose starch (CLHAS) matrix was used as a biodegradable drug delivery implant for the prevention and treatment of osteomyelitis. Thirty-two dogs underwent the femoral insertion of a screw inoculated with Staphylococcus aureus and were then randomly assigned to four groups: (A) prevention with ciprofloxacin-CLHAS implants, (B) surgical debridement (positive control), (C) surgical debridement and oral ciprofloxacin treatment and (D) surgical debridement and treatment with ciprofloxacin-CLHAS implants. At week 4 the osteomyelitis was confirmed, the infected site debrided and respective treatments initiated for groups B, C and D. Radiographs, macroscopic evaluations, bacterial cultures and histopathological examinations were used to evaluate the femora at week 10. Femora from preventive group A were almost normal. Dogs of both ciprofloxacin treatment groups C and D showed better bone healing, less periosteal reaction and less screw mobility than dogs from group B. Eradication of infection was observed at proximal/distal sites in B: 25%/12%, C: 37%/62% and D: 62%/75%. Both ciprofloxacin treated groups improved radiographically from week 4 to week 10. Periosteal and marrow neutrophilic and lymphoplasmocytic infiltrations were less severe in groups C and D versus group B. These data suggest that biodegradable ciprofloxacin-CLHAS implants are a safe and efficient modality for the prevention and treatment of osteomyelitis.

A systematic review of animal models for Staphylococcus aureus osteomyelitis

“…One macroscopic approach or lesion scoring employs the Rissing scale (Rissing et al , 1985b; Shandley et al , 2012), converting the appearance of infected bone into a quantitative scale: 0 = no visible evidence of infection; 1 = minimal erythema without bone destruction, without abscess; 2 = erythema with bone formation and minimal bone destruction; 3 = abscess with new bone formation, bone destruction and with purulent exudates; 4 = severe bone resorption, abscess, and total bone involvement. Studies performing a histologic examination of bone samples, such as Huneault et al , analyzed periosteal proliferation, cortex remodeling, endosteal proliferation, periosteal neutrophilic inflammation, periosteal lymphoplasmocytic inflammation, marrow lymphoplasmocytic inflammation, sequestrum and bacteria (Huneault et al , 2004; Petty et al , 1985). …”

“…After twelve weeks, each specimen revealed radiographic, clinical, histological, and microbiologic evidence of osteomyelitis. Another canine model uses the lateral aspect of the femur, in which S. aureus is directly dripped onto a 2.0 mm cortical screw, which is subsequently placed through cortex with the end of the screw resting in the intramedullary cavity (Huneault et al , 2004). …”

Efficacy of ciprofloxacin implants in treating experimental osteomyelitis

“…Various experimental animal models, such as rats,9–15 rabbits,16–26 dogs,27–29 or guinea pigs,30 have been used to search for suitable treatments for human osteomyelitis. Although rats are handy, inexpensive animals, it is difficult to extract the implanted system for later characterization because of the small femurs size 31.…”

A large animal model for a failed two-stage revision of intramedullary nail-related infection by methicillin-resistant Staphylococcus aureus

“…More recently, a large animal model was used in the evaluation of antimicrobial implant surfaces as a prophylaxis against infection in a sheep model of plate osteosynthesis Stewart et al, 2012), resembling other large animal models for prevention of infection using bone cement beads and spacers (Petty et al, 1988;Wenke et al, 2006). The treatment of an established infection has been less frequently covered in the literature, with one study in dogs describing antibiotic-eluting bone cement in a simple bone defect model (Fitzgerald, 1983) and a second canine model of infection associated with a cortical screw (Huneault et al, 2004). A goat model for open wound infection has also been described (Stinner et al, 2012).…”