A new experimental model of acute osteomyelitis due to methicillin-resistant Staphylococcus aureus in rabbit

Abstract

Aims: To assess the impact of antibiotic therapy on severe osseous infections, animal models of chronic bacterial infections have been developed; however, these models suffer from many experimental limitations. The aim of this work was to develop a new model system in which high levels of bacteria are obtained within femoral bone marrow and bone tissue, and such infections are maintained for at least 14 days. Methods and Results: Experimental osteomyelitis was induced in 25 New Zealand white rabbits. A 109 CFU ml−1 suspension of methicillin‐resistant Staphylococcus aureus was injected into the knee after bone trepanation. On day 3, surgical debridement was performed to mimic a surgical procedure. Animals were euthanized 1, 2, 3, 9 and 14 days post‐inoculation to determine the bacterial counts in marrow and bone, and to evaluate the stability of the infection. Inoculated lesions also were assessed for changes in histological parameters on days 3 and 7 post‐inoculation. At days 1, 2, 3, 9 and 14 post‐inoculation, we observed 6·50 ± 0·64, 7·30 ± 0·49, 7·82 ± 0·19, 8·00 ± 1·48 and 8·99 ± 0·20 log10 CFU g−1 in bone marrow and 8·40 ± 0·68, 7·65 ± 0·27, 7·58 ± 0·30, 8·88 ± 0·52 and 8·28 ± 0·39 log10 CFU g−1 in bone tissue, respectively. No statistical differences in bacterial count were found between bone marrow and bone tissue at any time point. Conclusion: This new model of acute osteomyelitis was validated by histological and microbiological changes in the absence of sclerosing agents, and these changes remained stable for 14 days. Significance and Impact of the Study: These results describe a new experimental model of acute osteomyelitis and demonstrate its usefulness in assessing the activity of antibacterial agents in vivo soon after bone infection.

Experimental model of biofilm implant‐related osteomyelitis to test combination biomaterials using biofilms as initial inocula

“…44 Importantly, there were no sclerosing agents used in this study to promote the development of osteomyelitis, whereas in previous studies, these noxious agents have been commonly used to initially kill bone and/or tissue with the intent to make it more susceptible to infection. [45][46][47][48] In addition, the model in this study also appeared to circumvent the problem of low reproducibility for the induction of osteomyelitis, which was cited by Gaudin et al 49 as an important limitation of animal models of osteomyelitis.…”

pH-controlled delivery of gentamicin sulfate from orthopedic devices preventing nosocomial infections

“…Bacterial growth, and so inefficiency of the bioactive biomaterial, was characterized by cloudy BHI. MRSA strain was obtained from blood cultures (gentamicin MIC b0.5 μg/mL) [34].…”

Using biofilms as initial inocula in animal models of biofilm‐related infections

“…Thus, when planktonic cells are used in in vivo models, it may be that the majority are eradicated before they can form biofilms. This may contribute to the low reproducibility for the induction of osteomyelitis, which has been suggested by Gaudin et al47 as a common problem with animal models of osteomyelitis. (2) It is well documented that planktonic bacterial cells are more susceptible to antibiotics than those residing in a biofilm 48, 49.…”