Our aim was to review the success of different approaches to the treatment of infected EPRs in our centre in order to improve outcomes and identify patients at high risk of recurrent infection. We have shown that compromised local soft tissue status, prior surgical treatments for infection, the type of surgery, and infection with Enterococcus spp are all associated with a higher risk of recurrent infection.

The association between poor soft tissues and recurrent infection has been described in several studies involving prosthetic joint infection (PJI) patients [4, 11]. Among our cohort, 75.1% of patients had at least one of the criteria associated with compromised soft tissues. Patients undergoing EPR for oncological conditions are more likely than others to have compromised soft tissues as the index procedure often requires resection of soft tissues including bone, and some patients have radiotherapy. The most common soft tissue problems in our cohort were sinus, radiotherapy damage, large dead space defects, and open wounds. The importance of soft tissue cover means there should be a low threshold for involving a plastic surgical team as part of multidisciplinary management.

The microorganisms associated with an infected EPR are similar to conventional PJI at first infection. These are predominantly coagulase-negative staphylococci (30 to 43%) and Staphylococcus aureus (12 to 23%), followed by polymicrobial infections (10 to 11%) and streptococci (9 to 10%). There are a small number of first infections with Gram-negative bacilli (3 to 6 per cent), enterococci (3 to 7%) and anaerobes (2 to 4%), but these become more common with subsequent episodes of infection, likely due to selection pressure after successive treatments with surgery and antibiotics. These microorganisms are often resistant to conventional antibiotics and are considered difficult to treat in PJI algorithms [12, 13]. Our data support the need for prosthesis removal where the infection is caused by Enterococcus spp.

We defined recurrent infection based on clinical findings regardless of whether the same pathogen was involved. 57% (24 of 42) of recurrent infections involved the same organisms as the preceding episode, suggesting that these represented relapses rather than new infections. The high overall relapse rate likely reflects the difficulty associated with two-stage exchange after EPR surgery, when the use of custom and very large implants makes the removal of an implant and the use of a spacer challenging.

Although silver-coated EPRs may have an antimicrobial effect, we did not find a reduction in the risk of recurrent infection, which is consistent with other studies [5].

When a second-stage reimplantation was performed, two-stage exchange had the highest success rates (82.8% at 12 months, 79.3% at 2 years and 61.0% at 4 years). Our results are comparable to others which report success rates of 63 to 100% [4,5,6]. Jeys et al. reviewed 58 patients treated with a two-stage exchange for infected EPR. 72% of patients were infection-free at 24 months [6]. Sigmund et al. reported a success rate of 62% at 48 months following a two-stage exchange [5]. The authors suggested their lower success rate was due to a lower proportion of patients (18 of 32 (56%)), having removal of all prosthetic stems. In their subgroup analysis, the success rate for patients who had removal of all implants was nearly three times higher than those who had a retained stem (22% vs 64%). In our series, all patients with a two-stage exchange had removal of all stems. 37% (17/46) of patients for whom a two-stage exchange was planned, did not have a second-stage reimplantation. The most common reasons for not undergoing a second-stage procedure were refusal by the patient, and concerns about severe medical comorbidities or poor soft tissues. When these patients are included, the success rate of patients selected for two-stage exchange is lower (71.2% at 12 months, 69.0% at 2 years and 55.3% at 4 years). Published studies which do not include this group may therefore overestimate the overall success rate of two-stage exchange. Nevertheless, our finding that a two-stage exchange is associated with the lowest risk of recurrent infection is consistent with the international consensus for the treatment of chronic EPR infection [14].

A one-stage exchange avoids the use of a spacer and is therefore attractive. Algorithms for revision arthroplasty recommend that one-stage exchange can be considered in early or low-grade infections with good soft tissue coverage and caused by pathogens sensitive to biofilm active antimicrobials [12, 13]. In revision knee arthroplasty, when these criteria are met, high success rates between 70 to 95% at 4 years have been reported [12]. Oncological EPR studies have lower success rates: Hardes et al. reported a 33% success rate at a mean follow-up of 32 months (0.3–128 months) and Jeys et al. 42% at a mean follow-up of 5.8 years (range 0.3–34 years) [6, 11]. Our success rates are broadly comparable, with 63.6% at one year, 45.5% at 2 years and 36.4% at 4 years. The high frequency of local soft tissue compromise and difficult-to-treat organisms, particularly in patients with a history of multiple revisions and oncological surgery, significantly limits the number of patients who meet the established criteria for one-stage exchange.

DAIR may be an attractive choice for well-fixed or custom, particularly joint-sparing implants. Success rates in PJI range from 50 to 70% in selected cases when specific criteria are met [12, 13]. These include early infections with symptom onset within 4 weeks, good soft tissue coverage and susceptible organism(s) sensitive to available antibiotics. The success rates in EPR studies are highly variable, between 39 and 70% [1, 15]. Most have small numbers and variable follow-up periods, and none provide a full description of the procedure. The success rate in our study was 44.6% at 2 years. As it may only be possible to change part of a large prostheses there may be limits to what can be achieved without exchanging all the implant components, particularly if the soft tissues are compromised.

DAIRs without exchange of modular components, when attempted as a definitive procedure for infection, were associated with the highest infection recurrence rate, of over 70% at 2 years. Although debridement may provide source control for sepsis, it is unlikely to eradicate infection and should not be considered a definitive treatment.

Our overall success rates are lower than published studies, which seldom include a large sample of salvage procedures and multiply treated EPRs [5, 6, 9]. We consider our study more representative of real-life clinical practice and provide important data that will better inform everyday decision-making. EPR infection remains difficult to manage and some patients inevitably require amputation. The overall amputation rate for infection of 21% in our study is similar to other studies [16].

Our findings have implications for the provision of services for patients with EPR infections. We recommend that patients be promptly assessed and investigated for a microbiological diagnosis and optimisation of soft tissues as part of an infection MDT before deciding on treatment intent.

Our study benefits from a relatively large cohort with long follow-up. All patients were included in the cohort, and none were lost to follow-up, minimising the risk of selection bias. Although a relatively large sample, this is a heterogeneous population undergoing a range of procedures for a wide range of conditions and our study is too small to detect small effects on outcome. Although the effect of confounding variables was considered, our study was retrospective which increases the possibility of unmeasured confounders.