Influence of fracture stability on Staphylococcus epidermidis and Staphylococcus aureus infection in a murine femoral fracture model

Abstract

Fracture-related infection (FRI) is a major complication in surgically fixed fractures. Instability of the fracture after fixation is considered a risk factor for infection; however, few experimental data are available confirming this belief. To study whether stable fractures led to higher infection clearance, mouse femoral osteotomies were fixed with either stable or unstable fixation and the surgical site was contaminated with either Staphylococcus epidermidis (S. epidermidis) or Staphylococcus aureus (S. aureus) clinical isolates. Infection progression was assessed at different time points by quantitative bacteriology, total cell counts in spleen and lymph node and histological analysis. Operated, non-inoculated mice were used as controls. Two inbred mouse strains (C57BL/6 and BALB/c) were included in the study to determine the influence of different host background in the outcome.Stable fixation allowed a higher proportion of C57BL/6 mice to clear S. epidermidis inoculation in comparison to unstable fixation. No difference associated with fixation type was observed for BALB/c mice. Inoculation with S. aureus resulted in a more severe infection for both stable and unstable fractures in both mouse strains; however, significant osteolysis around the screws rendered the stable group functionally unstable.Our results suggested that fracture stability could have an influence on S. epidermidis infection, although host factors also played a role. No differences were observed when using S. aureus, due to a more severe infection, leading to osteolysis and loss of stability in both groups. Further studies are required in order to address the biological features underlying the differences observed.

IL-6 signalling protects zebrafish larvae duringStaphylococcus epidermidisinfection in a novel bath immersion model

“…S.epidermidis has recently emerged as an important opportunistic pathogen that causes frequent nosocomial infections. Owing to the natural occurrence of the bacteria as commensals on human skin, it is a common cause of acute sepsis in premature neonates and immunocompromised individuals (Sabaté Brescó, Marina et al, 2017). It is the single largest cause of infections in implants and indwelling medical devices (Otto, 2009; Uçkay et al, 2009).…”

“…The high prevalence of multi-drug resistant strains, particularly in the clinical setting as well as the increasing incidence of such infections have made S.epidermidis infections a serious burden for health-care world-wide. For example, S.epidermidis alone accounts for ~22% of bloodstream infections in intensive care setting in the US, ~30% of orthopaedic-device related infections that may increase up to ~50% in developing countries, and 15-40% of prosthetic valve endocarditis (Le et al, 2018; Otto, 2009; Sabaté Brescó, Marina et al, 2017).…”

Recommendations for design and conduct of preclinical in vivo studies of orthopedic device‐related infection

“…Certain situations, however, may demand a complex model to fully assess the device even in a basic science study, particularly when the function of that device can influence the biology of the surrounding tissues. For example, a technology to prevent infection in patients receiving a fracture fixation device may need to be tested in a model that includes a fracture or soft tissue damage, since biomechanical forces and soft tissue damage influence the healing response of bone, which can also influence host antibacterial defenses . Similarly, fracture models will also allow estimation of the impact of the technology on fracture healing in addition to the antibacterial efficacy, which is also a key outcome for both basic science and regulatory approval.…”

“…Some human devices are simply too large for application in certain species, and so the ability to produce and use a smaller, analogous “copy” at reasonable cost, and still recapitulate the human situation is important. With functional fracture fixation implant systems available for mid‐size animals such as rabbits and even smaller animals such as rats and mice, definitive studies may focus on the model with most clinical relevance, rather than on size alone. It should be noted, however, that many types of medical devices, including total joint prostheses, are extremely difficult or impractical to miniaturize or apply in animals within reasonable burden limitations.…”

An Enzybiotic Regimen for the Treatment of Methicillin-Resistant Staphylococcus aureus Orthopaedic Device-Related Infection

“…Mice underwent an initial operation to create a femoral osteotomy, which was repaired with a 4-hole titanium MouseFix plate with analgesia and anesthesia as previously described [68]. At the time of surgery, mice were inoculated with 10 4 CFU of SA strain USA300 at the logarithmic growth phase.…”