Orthopaedic device-related infection: current and future interventions for improved prevention and treatment

Abstract

Orthopaedic and trauma device-related infection (ODRI) remains one of the major complications in modern trauma and orthopaedic surgery.Despite best practice in medical and surgical management, neither prophylaxis nor treatment of ODRI is effective in all cases, leading to infections that negatively impact clinical outcome and significantly increase healthcare expenditure.The following review summarises the microbiological profile of modern ODRI, the impact antibiotic resistance has on treatment outcomes, and some of the principles and weaknesses of the current systemic and local antibiotic delivery strategies.The emerging novel strategies aimed at preventing or treating ODRI will be reviewed. Particular attention will be paid to the potential for clinical impact in the coming decades, when such interventions are likely to be critically important.The review focuses on this problem from an interdisciplinary perspective, including basic science innovations and best practice in infectious disease. IntroductionOrthopaedic and trauma device-related infection (ODRI) remains a major complication in modern trauma and orthopaedic surgery. 1 Despite best practice in medical and surgical management, neither prophylaxis nor treatment of ODRI is effective in all cases, and can lead to infections that negatively impact clinical outcome and significantly increase healthcare expenditure. 2 Pre-operative and correctly-timed prophylactic antibiotic intervention is mandatory for a majority of orthopaedic procedures. However, despite this, the incidence of infection following elective orthopaedic surgery is in the range of 0.7% to 4.2%, 3-7 while the incidence can be much higher in trauma cases where infection rates range from approximately 1% after operative fixation of closed low-energy fractures, to more than 30% in complex open tibia fractures. 8,9 Treatment success rates vary, with between 57% and 88% often reported. [10][11][12] Current curative approaches (radical debridement, revision surgery and prolonged antibiotic therapy) often result in significant socioeconomic costs, not to mention the risk of life-long functional impairment for the patient. Against this background, and with the increasing issue of antibiotic-resistant bacteria, the problem of ODRI is set to continue to pose a challenge for practising clinicians in the coming decades. The clinical and microbiological challenges of modern device-related infectionsThe most prevalent species in ODRIs are Staphylococci. [13][14][15][16][17] Staphylococcus (S.) aureus accounts for between 20% and 30% of cases of infection after fracture fixation and prosthetic joint infections (PJI), with coagulase-negative staphylococci (CoNS) accounting for 20%-40% of cases, [13][14][15][16] including small colony variants. 18 Other Gram-positive cocci including Streptococci (1%-10%) and Enterococci (3%-7%) are less frequently encountered. Infections caused by Gram-negative bacilli, including Pseudomonas aeruginosa and Enterobacteriaceae account for approximately 6%-17%, [13][14][15][16...

Controlled Release of LL‐37‐Derived Synthetic Antimicrobial and Anti‐Biofilm Peptides SAAP‐145 and SAAP‐276 Prevents Experimental Biomaterial‐Associated Staphylococcus aureus Infection

“…Strategies to prevent BAI include the development of antibiotic‐releasing implant coatings . However, such coatings may promote the emergence of antibiotic resistance .…”

“…Obviously, there is a very pressing need for the development of novel agents and strategies, e.g., efficient coatings and delivery systems, to replace or complement current antibiotics for the treatment of BAIs . Antimicrobial peptides (AMPs) are considered promising treatment alternatives owing to their broad range activity and their mode(s) of action being different from those of conventional antibiotics.…”

Self-defending additively manufactured bone implants bearing silver and copper nanoparticles

“…4 Since in this case the antibacterial agents are applied directly at the implantation site, the required dose is lower as compared to systemic intake, thereby decreasing the side effects. 5 Inorganic nanoparticles (NPs), such as silver (Ag) and copper (Cu) have been explored as alternatives to antibiotics that suffer from ever increasing bacterial resistance. 6,7 The large surface area of NPs leads to their amplified oxidation on the implant surface while the accompanying release of metallic ions induces strong bactericidal effects.…”

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

“…Considering the risks and mechanisms of infection development around implanted orthopedic devices, coupled to an increasing number of surgically placed orthopedic devices expected globally over the coming decades, there is a clear need for improved technologies to prevent, diagnose and treat ODRI . The established pathway to clinical implementation for any anti‐infective technology proceeds from preclinical (in vitro and in vivo) testing followed by clinical evaluation.…”