this entry was modified by a paper by E. C. RODRIGUEZ-MERCHAN, MD, PhD a Consultant Orthopaedic Surgeon at La Paz University Hospital, Madrid, Spain and Associate Profesor of Orthopaedics, University Autonoma, Madrid, Spain.
introduction
Deep infections are among the most severe complications in total knee arthroplasty. Infection rates described in the first series published were as high as 23%.1-3 In more recent papers, the figure ranges between 1% and 2%.4 In a recent review of 6,489 knees, this figure was brought down to 0.4% in primary surgeries and 1% is prosthetic revisions.1-3
ASSESSMENT OF RISK FACTORS
Appropriate patient selection and a correct preoperative assessment are fundamental to determine whether the benefits of the surgery may be outweighed by its risks. Rheumatoid arthritis, diabetes mellitus, immunosuppression treatment, psoriasis and previous infections in the knee are the risk factors most clearly related with TKA infection.
Some risks are universal: Lack of vascularization in the prosthesis itself hampers the arrival of antibiotics and cells from the immune system. Tissue-initiated dissemination is the only mechanism through which they can reach the infected area. Also, interaction between the prosthetic components and the host seems to lower the patient's defense mechanism. (The combination of metal particles, polyethylene and polymethyl-methacrylate (PMMA) reduces the destructive and chimiotactic activity of polymorphonuclears, which favors germ colonization PMMA is an easier prey to infection than titanium-aluminum-vanadium and cobalt-chrome alloys) Last, when an implant is introduced into the organism, a process is unleashed whereby protein molecules and cellular remains bind to it forming a glycoprotein layer, which can facilitate osseointegration and thereby hamper the adhesion of germs and thus infection. However, on some occasions, the first organisms to colonize these implant surfaces are bacteria, leading to the infection of the implant rather than to its tissular incorporation.
The microenvironment created around the bacterial film protects bacteria from the defenses of the organism. The different bacterial strains create a layer known as glycocalyx formed by exopolysaccharides that play a defensive role. Indeed, they inhibit the immune system and decrease complement activity, phagocytosis and antibiotic efficacy.
REDUCING RISKS
A thorough brushing on the hands and the preparation of the surgical field by means of iodophors seem to be the most effective techniques to reduce the amount of germs present on the skin. Preoperative antibiotic prophylaxis has shown itself to be an efficient method to lower infection rates.
Microbiology
The most pervasive pathogenic germs in infected TKAs are Gram-positive cocci. In several studies, the pathogens causing more than 50% of the infections were Staphylococcus Aureus and Staphylococcus Epidermidis.4 Other less frequent pathogens can also be found, like Gram-negative bacilli for example. This happens when the infection stems from hematogenous dissemination or an infection of the wound by relatively non-aggressive germs that provoke indolent and latent infections, such as streptococci, coagulase-negative staphylococci, anaerobic Gram-positive cocci, candidae and mixed flora.
Diagnosing TKA infections
Diagnosis should be based on clinical suspicion and on the carrying out of complementary tests to confirm it. Several classifications of infections have been proposed, depending on when the symptoms appear for the first time. Such classifications are useful to identify the type of bacteria present thus helping us plan our treatment. They can be divided into early, when symptoms appear within the first two months; intermediate, when they occur between 2 and 24 months; and late, when they emerge after 24 months.
Early infections
These appear during the immediate post-operative period and can be due to perioperative contamination. Diagnosis is easy when the infection is acute with purulent drainage, erythema over the knee or increased temperature. However, it can be more difficult when the cause of the infection is some low-virulence germ or the fact that the patient was previously subjected to long-standing antibiotic treatment. There is a tendency to administer oral antibiotics to treat any symptom, like redness around the wound, welling or drainage. But such treatment might be disguising the infection process and making it more difficult to isolate the germ.
Intermediate infections
These appear between the second and the twenty-fourth week. They are normally a sequela of perioperative contamination and tend to occur in patients who refer persistent pain, swelling or wound problems from the time of surgery.
Late infections
These appear after 24 months and are related with a hematogenous dissemination from some other site. It should be determined if the patient has suffered dental, GI or genitourinary surgery. In any form of presentation, it may be difficult to tell a non-infectious complication from a would infection or from a deep infection. The most significant symptom that should make us suspect an infection is the appearance of pain that requires a change in the usual analgesic treatment or that changes the normal progression of the whole process. We should rule out the presence of infection in all patients that refer changes in the intensity or type of their pain.
Complementary tests
There are a series of complementary tests that can help us confirm our diagnosis of prosthetic knee infection. Please note that none are "perfect" meaning that clinical judgment coupled with a good sense of the patient's needs drives clinical decision making.
Plain films
The appearance of rapidly-progressing radiolucent lines around the implant should make us suspect an infection. The resorption of subchondral bone and patchy osteoporosis can also be elements of suspicion. The presence of osteolysis is normally the most usual one, although the type of osteolysis found is normally fairly unspecific.
Laboratory tests
WBC levels are seldom too high. In a study of 73 infected knees, only 28% had counts over 11,000, the most usual average figure being around 8.300. ESR and CRP are useful tests to detect potential infections further to an arthroplasty. Values higher than 50 mm/hour have been observed in infected prostheses. However, there are both false positive and negative results. In short, ESR and CRP values should be carefully interpreted prior to considering a reoperation.
Bone scan
A bone scan can help us confirm a diagnosis. However its high cost and its inability to provide acceptable levels of sensitivity and specificity have restricted its use. We could say that bone scans can aid a prosthetic infection diagnosis, especially in doubtful cases, although it use should not used exclusively: it is simply not definitive.
Knee Aspiration
Aspiration of a joint is the most useful diagnostic test. False negative results are not rare and are usually due to the prolonged administration of antibiotics. For this reason, antibiotics should be suspended 10 to 14 days before carrying out the aspiration. A synovial fluid WBC count higher than 25,000/mm3 or containing more than 75% polymorphonuclear white cells, in addition to high protein and low glucose values will be suggestive of infection.5-8
Polymerase chain reaction (PCR)
This method is used to detect and amplify the presence of bacterial DNA. It is thought to be a quick method since it is not affected by whether the patient takes antibiotics or not. However, a high percentage of false positives has been detected, which might have been caused by any type of contamination. In short, it is a technique that can be used as a complement to the previous ones and whose usefulness may increase in the future.
Histological tissue study
In some cases an intraoperative histological study may be necessary. Indeed, it is advisable to take samples of the bone/prosthesis interface and of the synovial membrane. Gram staining is normally carried out, although it is a method that yields a high proportion of false negatives. A positive result would indicate the presence of infection whereas a negative one would not rule it out. The analysis of frozen histological sections is a more reliable technique to show the existence of infection.
A diagnosis of infected TKA cannot be based only on an isolated test. Clinical suspicion combined with lab tests, x-ray studies, aspiration and, finally, histological sections will lead us to a correct diagnosis we can subsequently use to design our treatment strategy.
Management of TKA infection
We have several options when it comes to managing an infected TKA. But before we select any of these, we must take into consideration a series of factors. These factors include the amount of time elapsed from infection, host-related factors, condition of the soft tissues, condition of the implant, type of microorganism present and its degree of sensitivity and, last but not least, the patient's expectations and functional needs.5-8
Planning for any one option requires having detailed clinical records, cultures, x-rays and information of previously received treatment. It is important to identify high-risk patients, i.e. those receiving immunosuppressor treatment or suffering from malnutrition or systemic disease, trying to improve their general condition as much as possible before surgery. Physical examination should provide information about the patient's neurovascular situation, their articular mobility, the condition of their extensor mechanism and their soft tissues as well as about any previous incisions or the need of skin coverage by a plastic surgeon. The final goal of treatment is to eradicate infection, ease the pain and preserve the limb's function.
Antibiotic suppression therapy and serial aspiration
The use of antibiotics as a sole technique has not delivered acceptable results, which leads us to think that is should be restricted to very specific cases. As mentioned above, the microenvironment generated around infected implants is such that eradication with antibiotics is practically impossible.
Indications for this type of treatment are as follows: impossibility to operate on the patient due to poor medical or anesthetic conditions; existence of low-virulence microorganisms amenable to be treated with oral antibiotics; good tolerance of antibiotics (without causing toxicity) and firm prosthetic fixation.
Antibiotic treatment should follow 3 basic principles: 1) Use of antibiotics of proven intracellular efficacy (rifampicin, fluorated quinolones, quatrimoxazole, clindamycin, phosphomycin, macrolides (azitromicine, clarithromycin), and the new antistaphylococcal agents (linezolid, quinupristin-dalfopristin). 2) Antibiotics should be combined, using a minimum of two to enhance the possibility of therapeutic success. 3) Long-standing administration, i.e. treatment should last a minimum of 6 months.
Debridement and prosthesis preservation
On some occasions, it is possible to debride the tissues and preserve the prosthesis. This treatment is indicated for acute postoperative infections or for acute hematogenous disseminations over well performing prostheses. The following criteria should be met for the result to be favorable: short delay from onset of symptoms (less than 2 to 3 weeks), Gram-positive germs, absence of prolonged wound drainage and presence of a stable implant.
The technique will consist in performing an wide-exposure arthrotomy so as to access every area in the joint. Subsequently, the PE insert is removed, which will make it possible to subluxate the joint and access the posterior area. A synovectomy must be performed, making an effort to make it as complete as possible, and multiple samples should be taken for the pathological study. The implants should be carefully inspected and their degree of fixation assessed. Later, antibiotic-impregnated bone cement beads can be applied. Vancomycin combined with tobramycin offers a wide-spectrum coverage. The wound is then closed and immobilized with a bandage. After a week of IV treatment, and once the microorganism has been identified, a new procedure is carried out to remove the cement beads and to perform a new debridement. Fresh samples must be taken and a new PE insert implanted. IV antibiotics should be administered along the next 4 weeks. Afterwards, depending on the germ present, the possibility of continuing the treatment will be assessed.
Carrying out a debridement comes across as an attractive option, although it is not exempt from difficulties (a complete synovectomy is impossible because of the difficulty to access all areas).5-8
Prosthetic (revision) replacement
Prosthetic revision surgery can be performed in a single stage or in two surgical stages, i.e. the old prosthesis is removed in a first procedure, and the new one is implanted in a second one.
Single-stage replacement
Indications to revise a prosthesis in a single-stage surgery are not clearly defined. Most authors seem to agree that if the infection has evolved less than 2 weeks, the isolated germ is Gram-positive and sensitive to antibiotic treatment, the soft tissues are in appropriate condition and the patient's general health is good, then a single-stage surgery can be envisaged. Results are extremely variable.
Two-stage replacement
The removal of all components, the carrying out of a wide debridement followed by a period of IV antibiotic treatment followed by the reimplantation of a new prosthesis remains the gold standard for the treatment of infected knee prostheses. Most of the existing guidelines for two-stage replacement comprise the withdrawal of the implant, an aggressive debridement of the bone and soft tissues and the complete removal of cement. Subsequently, high-dose antibiotic loaded cement spacers are placed and an antibiotic treatment will be administered for several weeks. The final implant will only be placed when the eradication of the infection has been confirmed, which can be done by means of repeated aspirations and cultures. In the intervening period, specific antibiotics should be administered, in accordance with the results of the cultures (Figures 1 and 2).
In methicillin-resistant germ infections, whose prevalence has significantly increased in the last decade, orthopedic surgeons should follow the current treatment guidelines. There are few studies on infections caused by methicillin-resistant organisms (S. Aureus, methicillin-resistant S Epidermidis and vancomycin-resistant enterococci).
In a recent study, Volin et al. 4 compared prosthetic infections from methicillin resistant and non-resistant bacteria that received the same type of treatment, i.e. two-stage replacement. This author obtained a 94% success rate in cases on non-resistant bacteria vs. 88.9% for resistant ones, although differences were not statistically significant. The conclusion of the paper is that two-stage replacement is an appropriate treatment both for methicillin sensitive and methicillin resistant organisms.
It would seem that the use of new antibiotics could improve results for resistant germs. The oxazolidinone linezolid is a new wide-spectrum antibiotic with very attractive pharmacokinetic and activity profiles. It is an antibiotic that acts against methicillin-resistant staphylococci and vancomycin-resistant enterococci. Its oral presentation makes its administration very convenient, reaching serum levels similar to those of parenteral administration. Its most significant - albeit reversible - side effect is myelosuppression. The usual dose is 600 mg BID for an average of 6 weeks. The studies available show that linezolid associated to an appropriate surgical treatment could be a good method to treat osteomyelitis and prosthetic infections.10
Use of antibiotic-loaded cement spacers
The introduction of PMMA mixed with high doses of antibiotics into the infected joint makes possible a local release of high doses of antibiotics, increasing the chances that the infection process might resolve.11-13 In general, the release rate of antibiotics from the cement where they are contained to their target environment proceeds at a rapid pace, which depends upon the cement type, the characteristics of the antibiotic, the dose used, the porosity and the contact surface. Cement beads or spacers, in the shape of a block, were used in order to preserve the length of the soft tissues. This facilitated a subsequent replacement in addition to releasing high doses of antibiotics into the joint at higher concentrations than could be achieved by intravenous administration.
Ever since spacers came to be used in the 80's, results have improved dramatically, with some series achieving 90% of successful results.14 Although results are excellent, the spacer block based system does have its drawbacks, mainly related to wound-healing and joint mobility problems that make the posterior approach difficult. For that reason, articulated spacers have been designed that allow the knee to move. They are of two types: the first type is entirely made of cement; the second tries to replicate a knee prostheses using both polyethylene and metal (PROSTALAC system). The goal of these systems is to permit mobility and partial weight-bearing in the period between surgeries, preserving soft tissue tension and articular stability.15-17
Knee arthrodesis
This method is used in few cases as first-line treatment. In general, arthrodesis can be considered a therapeutic option when some other of the techniques described above have failed, especially in young patients with high functional demands or in patients with large deformities, alterations of the extensor mechanism, damaged soft tissues, immunodepression or infections by extra virulent bacteria.1-3
Arthrodesis provides a stable and pain-free joint. However, the function of the knee is sacrificed, with all that this means for the carrying out of day-to-day activities. Note should be taken of whether other joints (the ipsilateral hip or ankle or the contralateral knee) are involved and of whether the contralateral leg has been amputated. Such circumstances will be contraindications for arthrodesis.
Resection arthroplasty
The purpose of this technique is to create a false joint that may allow a certain range of motion. The procedure consists in explanting the components and, after a wide debridement followed by antibiotic treatment the area is immobilized between 3 and 6 months. The purpose is to get the soft tissues to retract so that they can provide the area with a certain degree of stability. Candidates for this type of treatment are patients with polyarticular disease and few functional demands.
Limb amputation
This technique should be considered a last resort when treating a prosthetic infection. Its indications are as follows: an uncontrollable infection that threatens the patient's life, massive bone defects and severe soft tissue loss. Functional results tend to be extremely poor and patients often end up in a wheelchair.1-3
Conclusions
Two-stage revision arthroplasty is currently the gold standard for treating the infected knee prosthesis. Articulated spacers seem to be better than static ones. The survival rate free of implant removal for any reason is 90% at 5 years and 77% at 10 years.
References
1. Peersman G, Laskin R, Davis J, Peterson M. Infection in total knee replacement. Clin Orthop 2001; 392:15-23.
2. Kilgus DJ, Howe DJ, Stang A. Results of periprosthetic hip and knee infections caused by resistant bacteria. Clin Orthop 2002;404:116-24.
3. Hofman AA, Goldberg T, Tanner AM, Kurtin SM. Treatment of infected total knee arthroplasty using an articulating spacer: 2- to 12-year experience. Clin Orthop 2005;430:125-31.
4. Rorabeck CH. Salvage of the infected total knee replacement: infection: The problem. Clin Orthop 2002; 404:113-5.
5. Mont M, Waldmand B, Banerjee C. Multiple irrigation, debridement and retention of components in infected total knee arthroplasty. J Arthroplasty 1997;12: 426-34.
6. McLaren A, Spooner C. Salvage of infected total knee components. Clin Orthop 1996;331:146-57.
7. Wasielewski R, Barden R, Rosenberg A. Results of different surgical procedures on total knee arthroplasty infections. J Arthroplasty 1996;11:931-9.
8. Spangehl MJ, Hanssen AD. Management of the infected total knee replacement. Curr Opin Orthop 2002;13:1323-29.
9. Volin SJ, Hinrichs SH, Garvin KL. Two-stage reimplantation of total joint infections: A comparison of resistant and non-resistant organisms. Clin Orthop 2004;427:94-100.
10. Rao N, Ziran BH, Hall RA, Santa ER. Successful treatment of chronic bone and joint infections with oral Linezolid. Clin Orthop 2004;427:67-71.
11. Evans RP. Successful treatment of total hip and knee infection with articulating antibiotic components: A modified treatment method. Clin Orthop 2004;427:37-46.
12. Springer BD, Lee GC, Osmon D, Haidukewych GJ, Hanssen AD, Jacofsky DJ. Systemic safety of high-dose antibiotic-loaded cement spacers after resection of an infected total knee arthroplasty. Clin Orthop 2004;427:47-51.
13. Hanssen AD, Spangehl MJ. Practical applications of antibiotics-loaded bone cement for treatment of infected joint replacements. Clin Orthop 2004;427:79-85.
14. Haddad FS, Muirhead-Allwood SK, Manktelow AR, Bacarese-Hamilton I. Two-stage uncemented revision hip arthroplasty for infection. J Bone Joint Surg Br 2000;82B:689-94.
15. Haddad FS, Masri BA, Campbell D. The PROSTALAC functional spacer in two stage revision for infected total knee replacements. Prosthesis of antibiotic loaded acrylic cement. J Bone Joint Surg Br 2000;82-B: 807-12.
16. Hofman AA, Kane KR, Tkach TK, Plaster RL, Canargo NP. Treatment total knee arthroplasties using an articulating spacer. Clin Orthop 1995;321:45-54.
17. McPherson EJ, Lewonoski K, Dorr LD. Techniques in arthroplasty. Use of an articulated PMMA spacer in the infected total knee arthroplasty. J Arthroplasty 1995;10:87-9.
18. Younger AS, Duncan CP, Masri BA, McGraw RW. The outcome of two-stage arthroplasty using a custom-made interval spacer to treat infected hip. J Arthroplasty 1997;12:615-23.
19. Fehring TK, Odum S, Calton, TF, Mason JB. Articulating versus static spacers in revision total knee arthroplasty for sepsis. Clin Orthop 2000; 380:9-16.
20. Masri B, Duncan CP, Beauchamp CP. Long-term elution of antibiotics from bone cement: An in vivo study using the PROSTALAC system. J Arthroplasty 1998;13:331-8.
21. McLaren AC. Alternative materials to acrylic bone cement for delivery of depot antibiotics in orthopaedic infections. Clin Orthop 2004;427;101-6.
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