Elsevier

Biomaterials

Volume 27, Issue 11, April 2006, Pages 2331-2339
Biomaterials

Leading Opinion
The significance of infection related to orthopedic devices and issues of antibiotic resistance

https://doi.org/10.1016/j.biomaterials.2005.11.044Get rights and content

Abstract

Over the last 15 years, with the advent of modern standards in the control of sterility within the operating room environment and adequate protocols of peri-operative antibiotic prophylaxis, the incidence of infections associated to orthopedic implants has become very low. Nevertheless, the event of infection still represents one of the most serious and devastating complications which may involve prosthetic devices. It leads to complex revision procedures and, often, to the failure of the implant and the need for its complete removal. In orthopedics, for the enormous number of surgical procedures involving invasive implant materials, even if nowadays rare, infections have a huge impact in terms of morbidity, mortality, and medical costs.

The difficult battle to prevent and fight bacterial infections associated to prosthetic materials must be played on different grounds. A winning strategy requires a clear view of the pathogenesis and the epidemiology of implant-related infections, with a special attention on the alarming phenomenon of antibiotic resistance. In this regard staphylococci are the prevalent and most important causative pathogens involved in orthopedic implant-related infections, and, thus, the main enemy to defeat. In this paper, we offer an overview of the complexity of this battleground and of the current and new, in our opinion most promising, strategies in the field of biomaterials to reduce the risks and counteract the establishment of implant infections.

Introduction

Hip or knee replacements, fracture fixation, ligament and tendon reconstruction and other surgical implant procedures have in recent years become valid and extremely common procedures to restore the function of affected joints, fractured bone segments and impaired limbs. In the US alone, total hip and knee arthroplasties currently accounts for over half a million interventions each year [1], [2], [3]. In light of this enormous population of patients with orthopedic implants, even a currently low risk of infection, estimated to be in the range of 0.5–5% for total joint replacements (less than 1–2% in institutions with highly trained surgeons), has to be considered very relevant for its serious consequences. During the first 2 years following the interventions of total knee arthroplasty, infections have variously been reported as the second main cause of revision just after instability [1], [4], [5], [6], [7], when not even the first one [8].

Simple debridement procedures with retention of prosthesis and chemotherapy with antimicrobial agents are treatments that are not always effective on infections that are already established [9]. Sometimes prosthesis removal and replacement, when not even joint fusion [10], represent the only salvage option to definitively eradicate severe infections. These drastic interventions bear obvious implications in terms of attendant patient trauma, prolonged hospitalization as well as in terms of health and social costs (it has been estimated that the treatment of each single episode of infected arthroplasty costs >$50,000 [11]). Furthermore, following revision surgery there is also a significantly high risk (up to 10%) of a recidive and implant replacement, which has additionally to be taken into consideration.

In the strategy for the prevention of infections, much has been done to improve the operating standards, minimize the possibility of contamination during surgery, reduce the establishment of infection by peri-operative antibiotic prophylaxis, and confine pathogenic strains by patient isolation [12], [13]. Along these directions further improvements can still be made, but little advancements in terms of decreased infection rates are being expected in return of this type of efforts [14]. As a consequence, over the last 15 years, increasing attention has progressively been focused on the epidemiology and the pathogenesis of the infections, especially those associated to implant materials, in order to build knowledge and gain better control over this phenomenon. Many effort have been directed to investigate which are the most important etiologic agents involved, the pathogenetic mechanisms leading to microbial adhesion, colonization of implant surfaces, and evasion of the host defenses, the most crucial virulence factors, the nature and properties of microbial biofilms and, not last, the progressive alarming appearance of antibiotic resistant strains.

Section snippets

Pathogenesis of implant infections

The pathogenesis of peri-implant infections differs from that of other post-surgical infections for a series of phenomena that are strictly related to the presence of biomaterials. The interstitial milieu surrounding prosthetic implants is known to represent a region of local immune depression and a locus minoris resistentiae, often referred to as immuno-incompetent fibro-inflammatory zone [15], susceptible to microbial colonization, and favorable to the instauration of infections [16], [17],

Diagnosis of orthopedic implant-related infections and main pathogens involved

A fundamental and, at times, very difficult step in clinical orthopedic practice is the differentiation of the condition of implant infection from that of aseptic failure. While early post-operative and haematogenous prosthetic joint infections are often characterized by acute onset of symptoms and signs of infections, late post-operative prosthetic joint infections, which generally occur after the first 3 months following surgery, show more subtle signs of inflammation, chronic persistent

Antibiotic resistance

Antibiotic resistance is currently a main issue requiring primary clinical attention. Many important pathogens, S. aureus in first line among them, have long been recognized to exhibit always more alarming levels of antibiotic resistance [45], [46], [47]. Moreover, bacteria forming biofilms on prosthetic surfaces are per se particularly resistant to antimicrobials [48], [49], [50] and tend to survive to aggressive chemotherapy even in the absence of specific antibiotic resistance factors. In

Horizontal and interspecific spreading of virulence and antibiotic resistance factors

The several advancements in the knowledge of bacterial virulence and antibiotic resistance factors have recently provided a clearer view of the dynamics of bacterial populations and clones colonising human and environmental surfaces [53], [54], [55]. There is evidence that opportunistic saprophytes, regularly living on human epithelia and mucosae of healthy subjects, are characterized by a low equipment of virulence and antibiotic resistance factors. This normal flora, with less or null

Strategies to prevent implant infections

Significant advancements have currently been reached on the front of the medical treatment, once an implant infection has developed, in order to minimize its deleterious clinical consequences [61], [62]. However, there is no doubt that, as in other medical fields, prevention represents a main goal. Modern policy for the prevention of infections relies on a series of strategies on different ground levels. As said earlier, in the past decades, control of environmental and personnel contamination

Conclusions

In orthopedics as in many other medical fields the vast majority of post-surgical infections is associated to the presence of implant materials, which represent a site of weakness for the host defenses where even bacteria with a low level of virulence can easily establish. Given the enormous and steadily growing diffusion of patients with implant materials a successful control of the rate of post-surgical infections is mandatory. While many past efforts in this direction have mostly relied on

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    Editor's Note: This paper is one of a newly instituted series of scientific articles that provide evidence-based scientific opinions on topical and important issues in biomaterials science. They have some features of an invited editorial but are based on scientific facts, and some features of a review paper, without attempting to be comprehensive. These papers have been commissioned by the Editor-in-Chief and reviewed for factual, scientific content by referees.

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