A Rabbit Osteomyelitis Model to Simulate Multibacterial War Wound Infections

Abstract

A challenge facing military caregivers is the presence of multidrug-resistant infection in extremity wounds. Most frequently identified resistant strains are methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae (KP), Pseudomonas aeruginosa (PA), and Acinetobacter baumannii (AB). We adapted an existing osteomyelitis model to simulate an infected extremity wound for antibiotic testing. New Zealand White Rabbits (n = 95) were divided into 6 inoculation groups for infection with MRSA, KP, PA, and AB alone, and in multibacteria infections. Sodium morrhuate was injected into the left tibia to simulate blast wound trauma, then the respective bacteria or combination of pathogens, and finally sterile saline were injected. Colony-forming units for the mono-organism groups showed that AB, KP, or PA alone at 10(7) colony-forming units per mL (CFUs/mL) was effective for rabbit osteomyelitis induction. Colony-forming units for the multiorganism groups showed that the combination of AB (10(7) CFUs/mL)/KP (10(7) CFUs/mL)/PA (10(7) CFUs/mL)/MRSA (10(5) CFUs/mL) yielded a 100% osteomyelitis induction rate. At 8 weeks, however, only one mono-bacterial group and one multibacterial group showed significant radiographic improvement (p < 0.05). The rabbit model of osteomyelitis can be adapted to study infected blast wounds typical of those seen in veterans. To our knowledge, this is the first demonstration of the model simulating multibacterial infections with multidrug-resistant organisms.