Description of the condition
Over 1.5 million primary (first time) total joint prostheses (e.g. hips, knees) are implanted annually worldwide (Sorci Miller 2008). The incidence of infection associated with these types of prostheses has been estimated to be anywhere from 0.39% to 2.5% for primary total knee arthroplasty (Berbari 1998; Hanssen 1998; Peersman 2001; SooHoo 2006); 1% to 2% for primary total hip arthroplasty (Anagnostakos 2009; Berbari 1998; Hanssen 1998; Ong 2009); and 0.7% to 4% for other prostheses (i.e. shoulder, elbow) (Bohsali 2006; Little 2005). In developed countries such as the USA, there has been a close to two-fold increase in the incidence of infection in both hip and knee arthroplasties between 1990 and 2004 (Kurtz 2008). This infection burden is only expected to increase because the number of primary - and revision - procedures is expected to increase dramatically over the next 20 years (Kurtz 2008). Curing these types of infections requires removal of the implant, reimplantation of a revision implant, and long-term therapy with antimicrobial agents.
Not only do primary total joint prosthesis-associated infections increase the costs of health care, they can result in serious disability and mortality. Prosthetic infections have an overall mortality rate of 1% to 2.7% for patients around 65 years of age, increasing to 7% for patients who are over 85 years old (Fisman 2001). These infections require between three to four times the hospital and surgical resources required by (uninfected) primary replacement surgery (Herbert 1996), and costs to treat them stand at, or exceed, USD 50,000 (Jiranek 2006; Sculco 1993; Smith 2004). Infection has been estimated to extend hospital stay by 1.87 times for knee replacements (95% CI 1.85 to 1.88) and 2.21 times for hip replacements (95% CI 2.18 to 2.23) (Kurtz 2008). A conservative estimate of the total annual cost to treat these types of infections stands at USD 750 million (assuming a 1% infection rate of 1.5 million procedures at USD 50,000 per infection) but probably exceeds this number by a significant amount (based on the numbers above).
The development of antibiotic and antiseptic prophylactic guidelines from a systematic review of the literature (along with meta-analysis) may thus help reduce these events and their associated costs. The American Academy of Orthopedic Surgeons has recently identified antimicrobial prophylaxis as a priority for review, but, as yet, has not undertaken a systematic review of the evidence. Additionally, the British Orthopaedic Association cites in its guidelines for knee replacement that, "although there is no specific data relating to knee replacement, we believe that as with hip replacement, all patients should receive an intravenous broad spectrum antibiotic at induction of anaesthesia." (Glasgow 1999) Lastly, while the Scottish Intercollegiate Guidelines Network (SIGN) recently published recommendations for the use of antimicrobial prophylaxis against infection in the management of hip fracture in older people, it did not examine the use of antibiotic prophylaxis for hip implant surgery (SIGN 2009).
Implant-related infections also impose an emotional burden and suffering for patients who require treatment for them. These infections can often lead to functional impairment, long-lasting disability or even permanent handicap (Poultsides 2010). Curing them requires removal of the implant, followed by six to 18 months of rehabilitation to regain function comparable to the pre-infected state (Hillman 1995), though this state is rarely achieved (Poultsides 2010).
Implanted devices can harbour various micro-organisms within a layer of biofilm (i.e. a thin, resistant layer of micro-organisms such as bacteria, that form on, and coat, implant surfaces) surrounding the device (Donlan 2002). These biofilms develop on more than 25% of devices implanted during hospitalisation (Hazan 2006). These biofilm-embedded pathogens are more resistant to conventional antibiotic agents than their planktonic counterparts (micro-organisms floating or drifting within the circulatory system) (Gilbert 2003). Bacteria form biofilms as a basic survival strategy in any environment in which they proliferate (Donlan 2002). Biofilms protect bacteria from antibacterial chemicals (including natural antibiotics), environmental bacteriophages and phagocytic amoebae (i.e. help protect bacteria from their natural and unnatural predators). Bacteria form biofilms on smooth and rough surfaces with equal ease. Within a biofilm bacteria become encased in a protective polysaccharide matrix (carbohydrates joined by glycosidic bonds) that prevents predators from attacking the bacteria residing within or under it (Donlan 2002).
Description of the intervention
Protocols and guidelines have been developed for antibiotic and antiseptic prophylaxis for many different types of surgical procedure (Bratzler 2005; SIGN 2008), but none, to date, relate to primary total joint prostheses (Bratzler 2005; SIGN 2008). Such guidelines generally advocate antibiotic administration an hour prior to initiation of the surgical procedure and discontinuation 24 to 48 hours postoperatively (Bratzler 2005). The types of antibiotics commonly utilised with surgical implants include: cefazolin, vancomycin, cefepime, aztreonam, ciprofloxacin, levofloxacin, trimethoprim/sulfamethoxazole and linezolid (Darouiche 2003). Antiseptics are also generally applied to the incision site as part of skin preparation prior to incision. Commonly used antiseptics include chlorhexidine-alcohol, povidone-iodine, and combinations thereof. These guidelines, however, may not be applicable to primary total joint prostheses due to the potential formation of biofilms on the implant. As noted above, it is important to consider the impact that biofilm formation may play in determining the effect of various antibiotics.
How the intervention might work
When properly administered, prophylactic antibiotics significantly reduce the incidence of (non-implant) surgical infection (Classen 1992). The addition of antiseptics to antibiotic prophylaxis may further reduce the incidence of infections associated with primary total joint protheses. Although the Classen 1992 study assessed a patient population undergoing non-implant surgical procedures, the findings from this study indicated that antibiotics administered intravenously, up to one hour prior to the procedure, were most efficacious at reducing surgery-related infections. The findings from this study have become 'standardised' for all types of surgical procedures. This strategy has also been applied to the prevention of perioperative (i.e. occurring around the time of a procedure) infection in primary total joint prostheses (Fletcher 2007). There are, however, several issues regarding the use of antibiotic prophylaxis that remain unanswered.
Why it is important to do this review
Although a number of studies have examined the use of antibiotic prophylaxis with primary total joint prostheses, only two meta-analyses of the results (total hip and knee) have been published to date. The first meta-analysis examined primary total hip replacement (Glenny 1999), but ended up also evaluating antibiotic prophylaxis in studies where both total hip and total knee replacement were performed but were not considered separately. The authors of the systematic review did not follow up the authors of studies included in the meta-analysis, or manufacturers, for unpublished data. The review focused primarily on a comparison of the type of antibiotic in order to evaluate superiority; it did not use the 'accepted' criteria for defining a surgical site infection (SSI) (see below under types of outcome measures) (Horan 1992), and it did not examine operator experience, which has been identified as a predictor of infection rates in other types of implants (Mounsey 1994). The second meta-analysis was a review of English language publications only (AlBuhairan 2008), with a restricted definition of infection based on the presence of visible purulent exudate at the surgical site. Additionally, this review only examined primary or revision total hip replacement or total knee replacement, and limited the analysis of local antibiotic administration solely to antibiotic-impregnated cement. The systematic review we are undertaking will examine a number of other comparisons not made in the previous reviews (see Objectives). Furthermore, clinical guidelines have not been published for antibiotic prophylaxis used with primary total joint prostheses by two of the largest orthopaedic associations in the world: the American Academy of Orthopedic Surgeons and the British Orthopaedic Association (as noted above, a guideline has been published by BOA albeit without level 1 evidence).
A review of primary total joint prostheses (hip and knee) is needed for the following reasons: no one has performed a systematic review of the literature and meta-analysis on antibiotic prophylaxis for primary total joint prostheses; no evidence-based guidelines for preventing infections during these types of procedures have been published by leading medical associations; and development of specific guidelines (a potential result of this review) may help to reduce the incidence of these events and their implications and costs.