CORRInsights®: Blended Chitosan Paste for Infection Prevention: Preliminary and Preclinical Evaluations

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Excerpt

Orthopaedic infections are a challenging issue for both caregivers and patients. A former colleague who specializes in caring for patients with implant-related infections once told me that his patients undergo an average of six to eight surgeries before their first meeting. First-line management of this condition when it presents acutely might consist of irrigation and débridement, accompanied by the exchange of any modular elements of the implant, and administration of intravenous antimicrobials. Unfortunately, implant infections are characterized by the presence of drug-resistant biofilms, which can survive treatment by intravenous antibiotics. Common microbes typically encountered include Staphylococcus aureus, Staphylococcus epidermis, and Propionibacterium acnes. Most of these microbes can be killed by gentamicin, vancomycin, or cefazolin, among other drugs, but require high concentrations and long exposure times.
Many practitioners suspect that patient health plays a role in how susceptible a patient might be to infection [2], but large studies do not always control for patient age or immune status. We do know, however, that patients of advanced age or poor health status tend to be more susceptible to orthopaedic infection, and may not respond as well to treatment.
Multimodal management of this complex condition is important. Local antimicrobials, while capable of achieving concentrations thousands of times higher than systemic antimicrobials with minimal complications, must reach the biofilms to be effective. Anyone who has seen the débridement of infected granulation tissue is aware that there are major transport barriers to the distribution of antimicrobials in an infected wound. Only after definitive débridement can local antimicrobials be relied upon to scour the wound for residual disease and promote the return of healthy tissue.
Engineers and clinicians have sought to protect the surfaces of implants with low-dose delivery vehicles for several decades [3, 5]. It is difficult to assess the clinical efficacy of these prophylactic treatments due to low primary-infection rates. When fluid is leaving the wound bed via circulation and lymphatic uptake, low-dose depots are unlikely to maintain concentrations likely to kill biofilm for long enough to be effective due to fluid exchange. However, if there are planktonic bacteria are in the wound, these treatments may help to lower the overall bacterial load, and may help the body's own immune system prevent an infection from occurring.
Studies differ on the effectiveness of local delivery, both for prophylaxis and treatment [1, 4]. This controversy stems from differences in host health status, low primary-infection rates, differences in débridement techniques, and differences in antimicrobial susceptibility of the infections to the selected agents. Managing infections requires clinicians and microbiologists to understand transport from engineers, engineers and microbiologists to understand bacterial physiology from clinicians, and both clinicians and engineers to have a grasp of microbial behavior and susceptibility from microbiologists (in addition to the biomechanical issues which accompany débridement, joint replacement, and reconstruction). It is therefore unsurprising that so much controversy remains in this field.
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