Outcome of prosthesis exchange for infected knee arthroplasty: the effect of treatment approach

1Two-stage exchange arthroplasty has remained the gold standard in the treatment of infected total knee arthroplasties (TKAs) for over two decades. The original concept has been modified by several authors. Spacer block technique was first developed to avoid scarring of the joint during the interim period, and to work as a local antibiotic carrier. Later, articulating spacers were introduced to enhance the patient’s functional status and to maintain the range of motion during the period between the two stages to improve the often poor knee score and patient satisfaction. Irrespective of the type of spacer used, satisfactory outcomes in terms of infection eradication have been reported.

2Very little has been published on one-stage revision in the literature, but promising long-term results have been reported. The studies that have been published suggest that direct exchange may have a role in the management of infected knee arthroplasties, but this role is not clear at present. It is also unclear whether the type of spacer used in two-stage revision affects the outcome. Thus, we performed this systematic review to assess the effect of treatment approach on the outcome of infected knee arthroplasty.

3In January 2006, we searched several international databases using highly sensitive though somewhat unspecific search strategies, which are described in detail in Appendix 1. The literature search strategies were created in co-operation with a librarian. The research plan was reviewed and approved by the Finnish Office for Health Technology Assessment (see http://finohta.stakes.fi/).

4Two of the present authors (EJ and IS) reviewed the search results independently and classified the references found in terms of whether they should be included on basis of the title of the paper (Table 1), whether they should be excluded, or whether this was unclear. Abstracts of unclear references were reviewed and papers were then classified as being included or excluded. In addition to original study reports, review articles and articles dealing with the treatment costs of infected knee replacements were reviewed. Reference lists from all reviewed articles were assessed to complete the literature search. The two reviewers’ lists of papers that should be included were compared to each other, and where there was any discrepancy, they were re-classified according to the consensus reached. The list of articles included was reviewed by an expert on the subject who did not belong to the study group and it was found to fulfill the inclusion criteria.

5Finally, 25 original studies published in English and 6 studies published in other languages between 1983 and 2005 were included. The materials of several studies (,,,,,, Windsor et al. 2000,, ) were identical. In such cases, the most recent report was accepted for further analysis. In addition, reports by Booth and and presented partly overlapping data, but these studies were reviewed separately.

6Data about materials, methods, and results of each original article included was extracted into a specific form independently by EJ and IS. Each study was assessed using a checklist (Appendix 2). The checklist, based on previously published criteria for evaluation of the internal validity and generalizability of studies in systematic reviews, was customized for the context of this review. The quality score calculated was not used as an exclusion criterion.

7The materials extracted by EJ and IS were compared to each other and conflicting data were re-checked from the original papers and corrected after discussion.

8The principal outcomes were (1) the rates of new and recurrent infections and (2) the clinical outcome—measured as postoperative clinical knee score and range of motion—following the revision arthroplasty. Due to heterogeneity and to the low calculated quality scores in the reports, the study materials were not pooled using meta-analytical techniques. Instead, several graphs were prepared for the principal outcome variables in order to visualize any possible trend after sorting the materials by a potentially explanatory variable. A qualitative and descriptive summary of the results is also presented.

9The studies reported the results of 926 two-stage and 152 one-stage arthroplasties (Table 2). The number of operations reported in any one study varied between 5 and 104, and the average length of follow-up ranged from 12 to 122 months. In total, 3,718 and 986 case-years of follow-up were reported for two-stage and one-stage revisions, respectively.

10None of the studies included used a randomized or controlled trial setting. In 2 studies of two-stage revisions, historical comparison groups were used to analyze the effect of spacer type on treatment outcome. 5 studies stated that the materials had been collected in a prospective manner. In a considerable number of studies, either materials or the treatment intervention—or both—was incompletely described (Table 3). All the outcome variables of interest for this systematic review were reported in only 10 series. The total quality score ranged from 8 to 17 out of a maximum of 20 points. Quality score was not calculated for the 6 reports in languages other than English.

11Table 2 gives a summary of materials and treatment approaches of the studies reviewed. Measured by the number of cases and the total case-years of follow-up, best experience has been reported with static polymethylmethacrylate (PMMA) spacers (52 to 691 case-years of follow-up). Medium- to long-term follow-up has also been reported for resterilized prosthesis spacers (RPSs, resterilized removed femoral components with either a new or resterilized tibial polyethylene insert) and one-stage revision. The experience is shortest with articulating PMMA spacers (10–66 case-years) and with the ball-and-socket spacer, used to manage knees with remarkable ligamentous laxity and bony defects (30 case-years).

12In all studies, patients were given intravenous antibiotics after the first-stage operation, usually for 4–6 weeks. The details of antibiotic treatment (average length, antibiotic selection, use of oral antibiotics) were often unavailable, however, and only half of the studies reported the exact length of the interim period between the two stages (range of averages, 43–175 days). After reimplantation arthroplasty, a common protocol seems to have been to continue intravenous antibiotics until the results of operative bacterial cultures were ready. There appeared to be a correlation between publication year (rather than spacer type) and the duration of the interim period, with the most recent studies reporting shortest interim periods (data not shown). After one-stage revisions, antibiotics were given intravenously for periods ranging from 1–2 weeks to 4–6 weeks.

13There were no statistically significant differences in patient demographics (Table 2), types of detected pathogens (the proportion of staphylococcal species was 48–85%), or the quality score of the studies (not shown) between the studies concerning different spacer types or between the studies on two-stage or direct revision. The type of infection (acute vs. chronic) and the time from index arthroplasty to resection of the infected prosthesis were reported too seldom to enable comparison of the studies in these respects.

14Success in infection management was analyzed in three ways. Firstly, the total number of infections appearing after treatment was recorded, supplemented by the number of recurrent infections and of new infections (that is, postoperative infections caused by an organism other than the one detected upon treatment). After the index revision, deep knee infection was detected in 0–31% of cases. The treated infections recurred in 0–18% of the cases. The new infection rate varied from 0 to 31%.The length of follow-up did not appear to affect the rate of recurrent infections, but the reports with follow-up of < 4 years had few new infections (Figure 1).

15The lowest rates of recurrent infection were reported in studies where no spacer was used (0–5%) (Table 2). Also, resterilized prosthesis spacers, articulating PMMA spacers, and one-stage revision groups had low recurrence rates (0–6%, 0–7%, and 0–6%, respectively). No association was seen between type of spacer and the rate of new infections, although in the ball-and-socket spacer series with relatively young patients an exceptionally high number of new infections was reported (31%). The indication for primary arthroplasty (osteoarthritis or other), mean age, or the pathogen idenepsied did not appear to affect the incidence of post-revision infection rates (data not shown). When the series were sorted by the year of publication, a decline in recurrent infection rate was seen in the most recent studies (Figure 2).

16Knee Society knee score and Hospital for Special Surgery knee score were used to measure the clinical outcome in most studies. Even more frequently, postoperative range of motion or maximal flexion was reported (Table 3). Preoperative scores were reported in 9 studies only. Comparisons between different treatment approaches were made in two ways: firstly, the studies were grouped by treatment approach (one vs. two stages) and spacer ideology (no spacer, static spacer, articulating spacer), and then different spacer types were analyzed separately.

17The highest average postoperative ranges of motion or maximal flexion exceeding 100 degrees (104–112 degrees) were achieved with articulating spacers, but the small study by also reported average flexion of 105 degrees (Figure 3). Other studies reported values ranging from 80 to 100 degrees. Despite the type of spacer, there was considerable variance so no definitive conclusions can be drawn. Most studies reported an average clinical score of at least 80 out of 100. No obvious trend was seen when clinical outcome was compared to any of the various explanatory variables (length of follow-up, revision type, spacer type). There was no difference in outcome with one-stage revisions and two-stage revisions.

18Data that can allow calculation of the change from preoperative to latest postoperative range of motion or clinical score were available in 9 studies. Except for 1 report, considerable improvement was seen irrespective of the spacer type. The highest improvements in clinical scores were achieved with static PMMA spacers or resterilized prosthesis spacers, while the change in range of motion was highest in series with articulating spacers. reported a series of 55 cases with static PMMA spacers, with an average follow-up of 62 months. During the follow-up, a decline in both clinical score (–6.7 points) and range of motion (–9 degrees) was seen.

192 studies comparing static and mobile spacers have been published. Clinical scores were not reported in these studies. In both studies, the static spacer group comprised a number of historical controls treated with static PMMA spacer. There was no statistically significant difference between shaped articulating PMMA spacers and static spacers regarding postoperative range of motion. In contrast, articulating spacers made of resterilized prosthesis components resulted in superior postoperative range of motion. This led the authors to conclude that the more the spacer resembles a real total knee prosthesis, the better the clinical outcome will be. In both studies the use of a historical control group introduces a time period effect as a confounding factor, which may partly explain the difference.

20Despite the relatively high number of reports on the treatment of infected TKAs with exchange arthroplasty, there is a lack of prospective comparative trials. Most of the studies reviewed were retrospective case series and failed to describe materials, surgical technique, or both in enough detail—thus making it difficult to compare the studies to each other. The studies published after the literature searches of our study do not appear to be any better in this respect (Table 4).

21Because of the heterogeneity of the studies and their materials, we could not use meta-analytical techniques. Instead, the studies were reviewed descriptively, which limits the objectivity of conclusions and leaves room for interpretative disagreement. To minimize the confounding effect caused by heterogeneous materials, only papers reporting a pure series of either one-stage or two-stage revision for deep knee infection were included. Consequently, some potentially relevant papers were excluded. Despite these exclusions, the papers included represent substantial experience in two-stage exchange arthroplasty especially, with over 3,000 person-years of follow-up documented.

22There was—and there still is—no question about the role of the two-stage approach being the gold standard in the management of infected knee replacements. Thus, our aim was to detect any factors that might have a relationship with the outcome variables under study. A trend suggesting such a relationship was found between the type of spacer and the rate of recurrence of infections, and also between the type of spacer and postoperative range of motion (or maximal flexion). However, as it appears that recurrence rate has declined over the past 2 decades (Figure 2; Goldman et al. 1996, Hirakawa et al. 1998, Haleem et al. 2004, Sheng et al. 2006), and articulating spacers have been introduced quite recently, it is unclear whether the low recurrence rate with articulating spacers is due to a decline in general recurrence rate or the type of spacer per se. With clinical scores and range of motion, the case-to-case variation was high and definitive conclusions could not be drawn from the present data. The results of the comparative studies may have been biased due to the use of historical control groups, or to differences in the length of follow-up.

23Spacers to be used during the interim period between resection and reimplantation operations were introduced to maintain joint cavity and to prevent contractures of periarticular soft tissues and, to thereby facilitate the reimplantation. Mobile spacers are thought to ease patients’ ambulation and prevent soft tissue contractures and muscle atrophy. In our study, no factors that could be reliably related to improved postoperative outcome were detected. A slight trend suggesting some advantage of mobile spacers over other types was seen, but only concerning range of motion (Figure 3).

24Though advantages of spacers of any type could not be proven, the results of our review and of the most recent reports strongly suggest that the use of articulating spacers—or even definitive new knee prostheses—does not affect the chances of eradicating an infection. However, foreign material and even antibiotic-containing bone cement may provide ground for microbial adhesion and bacterial growth; thus, spacers of any kind may encourage recurrence of infection. One should be prepared to remove an already implanted spacer and to redebride the joint in order to achieve control over the infection when markers of inflammation do not normalize or when the symptoms continue after the first-stage operation. For the same reason, two-stage revision (even without a spacer) may be the best approach in complicated cases, since a higher treatment failure rate has been reported in multiply-operated knees, in the case of resistant pathogens such as methicillin-resistant staphylococci, and in compromised hosts.

25A deep infection is an expensive complication and the outcome of two-stage revisions is probably worse than that of aseptic revisions. For these reasons, there has been increased interest in easier ways of managing infected TKAs. Unfortunately, pure antibiotic therapy, lavage procedures, and debridement with retention of the prosthesis have very limited indications. Thus, the question in practice is whether one-stage revision is an acceptable approach or not—or how the protocol of two-stage revisions could be improved.

26Although reinfection rates of only 9% and 11% after one-stage revision have been reported, the high failure rate of 27% per primum intentionem reported by von indicates that the outcome is not as predictable as that of staged exchange. No cost-effectiveness analyses have been published. Considering the probably catastrophic outcome of repeat revisions for septic failure, further studies are required to define the indications for this approach.

27Of the different modifications of the conventional two-stage approach, the recently reported protocol with shorter (2–3-week) antibiotic treatment has resulted in reasonable eradication rates, but at present only short-term follow-up is available and there have been no published studies comparing short antibiotic treatment with extensive antibiotic treatment. In most of the studies reviewed, a 4–6-week regimen was used and the antibiotics were selected according to the results of bacterial culture, but few publications have given details of the antibiotic treatment. This can be interpreted as indicating confidence in the importance of surgical intervention as opposed to the use of postoperative antibiotics, although the use of antibiotic-impregnated cement as local antibiotic carrier seems to be widely accepted. The optimal type and length of antibiotic therapy in exchange arthroplasty could not be gleaned from the results of this review.

28One of the major problems with the comparisons between the different treatment approaches used in this study is the possibility of selection bias. It is possible that the patients selected for one-stage revision or two-stage revision with mobile spacer prosthesis were healthier than those patients for whom two-stage revision was performed, for example, without any spacers. In such cases, the comparisons may be biased in favor of treatment alternatives, to optimize the changes to eliminate the infection. Such selection by surgeon’s preference would bias comparisons in favor of treatment alternatives other than the conventional two-stage exchange arthroplasty. Inclusion and exclusion criteria, and also the primary diagnoses and patient comorbidity indices were seldom reported. For these reasons, the confounding effects of host status and type of infection—and also of possible selection bias—could not be analyzed.

29The studies reviewed report rather similar success rates of 82–100% in eradication of infection. The rates are comparable to those of the more recently published series and to those of series published in languages other than English (Tables 2 and 4). The survival rates (77–80% at 10 years) are similar to the published survival rates of 85–90% following revision arthroplasty for infection in a nationwide series in Finland. Thus, it seems that the reports from specialized hospitals do not give over-optimistic results but that similar results can be obtained in different institutions.

30The factors that affect the outcome of exchange arthroplasty remain largely unknown. Clinical experience and studies on infected hip and knee arthroplasty suggest that host status (comorbidity), type of infection (acute vs. chronic), and the condition of the environment of the joint involved contribute to the outcome of infected knee replacement. These or any other factors that contribute to the outcome were not adequately analyzed in any of the studies reviewed. Because of the lack of detailed data on treatment failures, such analyses could not be performed using the results of this systematic review either. Future research should focus on the factors affecting the outcome of different treatment approaches.

31Most reports on exchange arthroplasty performed for infected knee arthroplasty are of poor methodological quality, and no unbiased comparative studies exist. The previously reported series included in this systematic analysis yielded similar success rates, but the factors that could predict the outcome are mostly unknown. In the light of our findings, two-stage revision with delayed reimplantation remains the gold standard. It seems reasonable to employ mobile spacers where possible, as they do not compromise the attempts to eradicate infection but may improve postoperative outcome. Despite some promising preliminary reports, the value of and indications for direct exchange arthroplasty remain unclear. Future studies focusing on these treatments should preferably use a prospective randomized setting and compare the new approach to the gold standard of two-stage exchange arthroplasty.