Characterization of a rabbit model of staphylococcal osteomyelitis

Abstract

We previously described a rabbit osteomyelitis model that involved the direct introduction of Staphylococcus aureus into devascularized bone. To further evaluate the model, we performed experiments aimed at correlating the microbiological, radiographic, and histologic parameters involved in the development of experimental osteomyelitis. Using the strain UAMS-1, we achieved an infection rate of 75% with an inoculum as small as 2 x 10(3) colony-forming units. However, development of significant radiographic and histologic signs of disease required an inoculum of at least 2 x 10(4) colony-forming units. Radiographic signs were minimal 1 week after infection and progressed steadily to a maximum 3 weeks after infection. In contrast, histologic signs of disease were observed within 1 week and remained essentially unchanged throughout the 4-week evaluation period. Unlike the results obtained with UAMS-1, rabbits infected with the heavily encapsulated Staphylococcus aureus strain Smith diffuse exhibited little evidence of disease even when infected with 2 x 10(6) colony-forming units. The reduced virulence of strain Smith diffuse was surprising given its greatly enhanced virulence (relative to UAMS-1) in a murine peritonitis model of staphylococcal disease. These results suggest that UAMS-1 expresses virulence factors that are important in the pathogenesis of osteomyelitis and that some or all of these virulence factors are either absent or are not expressed in strain Smith diffuse. Most importantly, the results suggest that our model may be appropriate for the identification and characterization of these virulence factors.

Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390

“…RN6390 was chosen for this comparison because it is the most commonly studied laboratory strain. UAMS-1 was chosen because it is a wellcharacterized virulent clinical isolate (Gillaspy et al, 1995;Smeltzer et al, 1997;Blevins et al, 2003), and because previous studies have indicated that UAMS-1 is genotypically very similar to other prominent clinical isolates, including EMRSA-16 (Cassat et al, 2005). UAMS-1 and RN6390 have also been shown to differ with respect to important clinically relevant phenotypes, such as biofilm formation Beenken et al, 2003;Cassat et al, 2005).…”

“…The fact that UAMS-1 does not make a-toxin, yet is virulent in animal models of osteomyelitis (Smeltzer et al, 1997) and septic arthritis (Blevins et al, 2003), is interesting in light of studies indicating that a-toxin makes an important contribution to staphylococcal virulence (Jonsson et al, 1985;Nilsson et al, 1999;Dajcs et al, 2002). While this could reflect the use of different animal models, there has also been a report indicating that the loss of haemolytic activity in S. aureus agr mutants is correlated with increased survival in vivo (Schwan et al, 2003).…”

Local Gentamicin Delivery From Resorbable Viscous Hydrogels Is Therapeutically Effective

“…Although scalability to human dimensions has not yet been shown, this model is well established in the literature. This model produces osteomyelitis reliably, provides surfaces for biofilm formation, and has been used to study various treatment protocols with discriminatory sensitivity to variations in treatment protocols [29,46,58]. Another weakness of the model is the capability of rabbits, on occasion, to clear infection postdébridement without local or systemic antimicrobials, confounding the analysis for response to treatment.…”

Preliminary investigations on a new gentamicin and vancomycin‐coated PMMA nail for the treatment of bone and intramedullary infections: An experimental study in the rabbit

“…The transverse sections of the femoral diaphysis and longitudinal sections of the distal epiphysis were acquired with a resolution of 300 dpi at different enlargements. Histologically, the disease severity score described by Smeltzer et al 44 was used to rate signs of infection; it is divided into four categories with a score from 0 to 4 points: intraosseous acute inflammation, intraosseous chronic inflammation, periosteal inflammation, and bone necrosis. The diagnosis of osteomyelitis was considered positive when the Smeltzer score was at least 4.…”