Novel model for studying hematogenous infection in an experimental setting of implant‐related infection by a community‐acquired methicillin‐resistant S. aureus Strain

Abstract

The aim of this study is to establish a new experimental model of hematogenous implant-related infection (IRI) by a communityacquired methicillin-resistant S. aureus (CA-MRSA) strain. Cylindrical porous tantalum intramedullary implants were inserted in the proximal right tibia of 30 male white rabbits after administration of antibiotic prophylaxis. Four weeks later and without antibiotic prophylaxis, 20 animals received 1 ml of inoculum of two different concentrations (study groups A and B) of CA-MRSA strain through an ipsilatelar femoral artery catheter. The remaining 10 received normal saline instead (control group C). Surviving animals were sacrificed 4 weeks later. Sterile bone, bone marrow biopsies, and implants were harvested for culture and histological evaluation. Ten animals receiving 5 Â 10 8 cfu/ml (group A) died within 48-72 h due to septic shock. Blood cultures were positive; histology demonstrated acute infection. Ten animals received bacterial load of 3 Â 10 8 cfu/ml (group B) and all survived; two had negative Gram-stain and cultures but PCR and RT-PCR results demonstrated the viability of the microorganisms, while periprosthetic osteolysis and histological evaluation indicated subacute osteomyelitis; eight animals established periprosthetic infection, osteomyelitis, and septic arthritis documented by positive Gram-stain, cultures, subperiosteal reaction, and chronic infection on histology. Control group specimens demonstrated no signs of infection. Histopathological semiquantitative scoring was used to compare the three groups. Comparison of groups A and B with control group and between group A and B showed statistically significant difference ( p < 0.05) in all parameters except for periosteal reaction between groups B and C ( p ¼ 0.354). This novel, reproducible experimental model will facilitate the study of hematogenous CA-MRSA IRIs. ß

Mouse model of hematogenous implant-related Staphylococcus aureus biofilm infection reveals therapeutic targets

“…Previous models of hematogenous orthopedic implant infections in rabbits and rats described the spread of the bacteremia infection to a surgically placed implant and surrounding bone and joint tissue but only at static time points after infection (29,30). Other models studied bacteremia that resulted in septic arthritis in mice but in the absence of a surgically placed implant (27,28).…”

“…To the best of our knowledge, two prior preclinical models of hematogenous orthopedic implant infections in rabbits (29) and rats (30) have described the hematogenous spread of infection to the implant and surrounding bone and joint tissue at static time points but have not investigated the temporal and spatial dynamics of the infection over time or determined relevant pathogenic factors.…”

A systematic review of animal models for Staphylococcus aureus osteomyelitis

“…Nine of these utilized a clinical isolate. MRSA strains included ATCC 33591, ST-021 (a clinical isolate from University of Maryland, Shock Trauma) (Craig et al , 2005), an MLST-80 clone (Poultsides et al , 2008), and the bioluminescent USA300 LAC:; lux strain (Niska et al , 2012). …”

“…Poultsides et al produced a hematogenous infection after insertion of a porous tantalum intramedullary implant press-fit into the proximal part of the tibia, which was capped by a silicone cup to permit load transmission within the knee joint (Poultsides et al , 2008). Four weeks later, the femoral artery was cannulated and a catheter was advanced to 2.0 cm proximal to the knee joint where 1 ml of bacterial inoculum was injected to maximize the implant exposure to bacteria.…”

Establishment of a new methicillin resistant staphylococcus aureus animal model of osteomyelitis

“…In the literature, one model of periprosthetic infection and systemic MRSA infection has been described [22]. Other models use a local MRSA inoculation, and many efforts have been made to develop new MRSA animal models, including the MRSA inoculation of rabbit knees [23] and rat bones [24].…”