Contemporary outcomes of debridement, antibiotics and implant retention in knee arthroplasty

Introduction

Periprosthetic joint infection (PJI) is a significant complication following knee arthroplasty. PJI involves the establishment of bacterial (the majority) or fungal infection of a prosthetic joint, and can occur at any time following implantation. The risk of PJI after primary knee arthroplasty is relatively low, ranging from 1–4%, and increasing to 8–10% for revision cases (1–3). As a reason for revision surgery, however, PJI is the indication in 20–25% of cases (4,5). Given the predicted increase in demand for knee arthroplasty, and a lack of evidence of decreasing infection risk, PJI represents a significant and ongoing challenge in modern orthopaedics (6-8).

PJI has a significant impact on patients’ quality of life and morbidity; with pain, reduced function, systemic sepsis, poor cosmesis, multiple surgeries and increased mortality all potential consequences (9,10). Treatment of PJI also places a significant burden on health care systems. From an economic perspective, revision of an infected knee arthroplasty is estimated to cost £30,000/revision, and predicted hospital costs of $1.6 billion for 2020 in the USA (2,11). A recent report from Finland provides further insight, with the excess cost of debridement, antibiotics and implant retention (DAIR) found to be €12,800 vs. €44,600 for a two-stage revision (hip and knee procedures combined) (12).

Contemporary management of PJI has built upon improved consensus on what features define PJI and the behaviour of causative organisms on prosthetic materials. The most widely accepted definition of PJI is provided by the Musculoskeletal Infection Society (MSIS) criteria, originally proposed in 2011, and updated at International Consensus Meetings (most recently in 2018) (13,14). The investigation and reporting of outcomes for PJI management has likely benefited, with a reduction in heterogeneity as to what constitutes an infected knee prosthesis. From a mechanistic perspective, advances have been made in understanding how organisms adhere and interact with artificial materials. In particular, the bacterial formation of, behaviour in and resistance mechanisms provided by biofilms are of particular interest. Given the majority of PJIs are caused by biofilm producing organisms this knowledge has contributed to the development of management schema. For a review of biofilms in PJI, readers are directed to a 2020 review by Shoji et al. (15).

In the setting of acute PJI, DAIR belongs to a spectrum of surgical treatment options, with single-stage and two-stage revision representing increasing levels of intervention and greater morbidity. DAIR comprises the thorough debridement and irrigation of the soft tissues, exchange of modular components (polyethylene trays, axes, bushes etc.) but the primary femoral, tibial, and patellar components are retained. This is combined with a period of antibiotics with good bone bioavailability, with the aim of infection eradication. The potential benefits of DAIR over a formal revision procedure are reduced tissue damage and greater functional outcomes (16,17). Outcomes for DAIR have been reported since the 1980s, with highly variable levels of treatment success. Some of this variability is likely secondary to heterogeneity in PJI definition, evolving surgical techniques and varied definitions of treatment ‘success’ over the years. As such, a review of modern DAIR outcomes is of value in patient counselling and treatment decisions.

Details regarding the diagnosis of PJI, indications, contraindications and surgical technique of DAIR are described elsewhere in this issue. The objective of this article is to review the contemporary outcomes of DAIR in the management of knee PJI over the last two decades.

DAIR in total knee arthroplasty

The evidence base for outcomes after DAIR in TKA PJI predominantly consists of cohort studies, of which most are retrospective, with small patient numbers and short follow-up. Kunutsor et al.’s meta-analysis of DAIR for PJI included 28 studies in which patients were treated from the year 2000 onwards. Of these 28 studies, 20 reported outcomes for less than 100 patients and only 2 had follow-up times greater than 5 years (18). As of yet, there are no randomised controlled studies reporting the outcome of DAIR in comparison to other treatment modalities.

DAIR success rate and PJI eradication

The most commonly reported outcome for DAIR studies is ‘treatment success’, but with wide variation in what constitutes failure and time points used. However, as with the definition of PJI, there have been advances in reaching a consensus definition. Diaz-Ledezma et al. published the results of an international Delphi method in 2013, defining a successfully treated PJI, and what constitute mid-term (>5 years) and long-term (>10 years) results (19).

Kunutsor et al.’s meta-analysis provides a valuable estimate of outcomes for DAIR, and included studies published prior to May 2017. The summary estimate, across all studies of knee DAIR, for infection control was 52.6% (95% CI: 45.10–60.10%). Furthermore, subgroup analysis of outcomes of knee DAIR by time period demonstrated a non-significant difference, with outcomes for studies prior to 2,000 having an infection control rate of 46.0% (95% CI: 30.9–61.5%) vs. 56.0% (95% CI: 45.7–66.1%) for studies from 2000 to 2017 (18). A search for reports of outcomes of knee DAIR published since this period yielded few additional results, but with treatment success rates in keeping with this meta-analysis (Table 1). Qu et al.’s pooled analysis of 1,266 cases of acute PJI demonstrated an overall success rate of 57.1% (18 of the included 33 studies included patients treated patient prior to 2000) (20). Iza et al. retrospectively analysed 26 acute post-operative and acute haematogenous knee PJI managed with DAIR. At a mean follow-up of 3.4 years 77% of patients were infection free, with acute post-operative infections having better success than acute haematogenous (93% vs. 58%) (21). Ottesen et al. published an overall success rate after DAIR for knee PJI of 84% in a series of 58 patients treated between 2008 and 2013, with a minimum 2-year follow-up. A retrospective multicentre observational study of 216 knee DAIRs performed in the United States between 2005 and 2015 found a lower success rate, treatment failure in 51% (90% of failures occurred within the first year) (22). Narayanan et al.’s analysis of 55 TKAs undergoing DAIR between 2009 and 2017 found an overall treatment success of 60% (23). Kim et al.’s retrospective comparison of outcomes between two-stage revision and two-stage revision after failed DAIR reported a total of 228 cases as treated with DAIR. Of these 228, 135 were defined as ‘successful’, equating to success for 59.2%, for cases identified between 2000 and 2015 (24). Bene et al. reported that 72.5% of 76 patients with acute PJI (between 2004 and 2012) treated with DAIR required no further operative intervention for infection, with a mean follow-up of 3.5 years (25). Duffy et al. report a treatment success of 69% in their retrospective review of 59 patients undergoing DAIR for PJI, with a median duration of 2.25 years (26). Weston et al. reported their experience of DAIR for acute knee PJI paired with long-term suppressive antibiotics. Their retrospective review of 134 infected TKAs between 2000 and 2014 demonstrated infection-free survival of 72% at 2 years, and 66% at 5 years (27). A treatment success of 88.0% was reported by Son et al. in a retrospective review of 25 cases between 2010 and 2014 managed with DAIR (28). Chang et al. reported their outcomes of a ‘modified’ DAIR technique for acute knee PJI, in which antibiotic impregnated cement beads are implanted in the medial and lateral gutters and suprapatellar space (and removed at 6 weeks), and compared them to standard two-stage revision. An infection control rate of 78% was demonstrated in both groups (9 knees in each group, treated between 2012 and 2013) (29). Finally, Leta et al. analysed 644 TKAs revised for infection as recorded in the Norwegian Arthroplasty Register between 1994 to 2016 to assess success after DAIR, one- and two-stage revision. This demonstrated a survival rate for revision for infection at 5 years as 79% after DAIR (and 87% for both types of formal revision) (30). A further subanalysis undertaken to assess influence of time period on outcome (1994 to 2004 vs. 2005 to 2016) did not find any significant differences. It should be noted that a limitation of this study is that treatment failure was defined as revision surgery, so would have excluded other treatments for PJI recurrence, making this estimate of success a likely overestimate.

Functional outcomes following DAIR

There are relatively few studies reporting the functional outcomes after knee DAIR for PJI (Table 2). Dzaja et al. retrospectively reviewed patient records from 1991 to 2011, and included the 12-Item Short Form Health Survey (SF12), Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Knee Society Scores (KSS). For those cases defined as ‘infection eradicated’ there were no significant differences in the SF12, WOMAC or KSS compared to outcomes for matched patients with non-infected primary TKA. Patients who failed treatment after DAIR demonstrated no significant difference in functional scores to patients having undergone two-stage revision, who’s scores were significantly worse than the matched primary TKA patients (17). Iza et al.’s report of 26 knee DAIRs between 2004 and 2016 found at the end of follow-up that patients with treatment failure had a mean KSS of 75, and those with success a score of 65 (non-statistically significant difference) (21). Aboltins et al. reported SF12 after DAIR in 37 cases (combination of hip and knees), and found no significant difference at 1 year for both the Physical Component Summary and Mental Component Summary of the SF12 compared to patients after primary joint replacement (31). Barros et al. similarly demonstrated no significant difference in patients after DAIR (for hip or knee PJI) as assessed by Hip Disability and Osteoarthritis Outcome Score or Knee Injury and Osteoarthritis Outcome Score, compared to matched patients after primary arthroplasty (32). These recent studies have not demonstrated significant differences in functional outcomes between successful DAIR and primary TKA, which is encouraging. No direct comparisons of functional outcomes after DAIR and staged revision were found. Yahgmour et al.’s systematic review of outcomes after single stage revision for TKA PJI did not include a meta-analysis due to outcome heterogeneity. However, functional outcomes were reported in some studies. These included KSS, with average scores of 42–72, and WOMAC, with average scores of 49.5–88 (33). A narrative review by Pangaud et al. reported mean KSS after single stage (80; range, 72–88) and two-stage revisions (78; range, 64–86). Range of motion was also reported, with a mean of 91.4° for single stage and 97.8° for two-stage revision (34). In comparison to the figures presented in Table 2, these suggest that DAIR is at least equivalent with regards to functional outcomes. However, this is based on comparisons between separate retrospective studies. In the management of hip PJI, there is evidence of superior functional outcomes (as assessed by the Oxford Hip Score) in patients treated successfully with DAIR vs. two-stage revision (16). Direct comparisons are needed in the management of knee PJI to determine differences in functional outcome between successful DAIR, one stage revision and two-stage revision.

Mortality following DAIR

Given the typically small retrospective cohort studies used to report outcomes after knee DAIR, a clear understanding of the influence of DAIR on mortality is difficult. Leta et al.’s analysis of the Norwegian register included 90-day and 1-year mortality rates after surgical treatments for knee PJI, however the register does not record cause of death. Approximately half (329 of 644) of the cohort analysed underwent DAIR, with a 90-day and 1-year mortality rate of 2.1% and 3.6% respectively (Table 3). One-stage revisions (72 cases) had a mortality of 0%, and for two-stage revision (243 cases) mortality rate of 1.2% and 2.5% (30). Weston et al.’s analysis of DAIR coupled with chronic antibiotic suppression included mortality rates. They report that DAIR for acute post-operative infection had a 5-year survival of 81% vs. 68% in the acute haematogenous group (27). There was no significant difference in 2-year mortality secondary to PJI in Kim et al.’s analysis of two-stage revision after failed DAIR vs. two-stage revision (1.3% vs. 1.6%) (24). Urish et al. reported a significant 5 year mortality of 19.9%, similar to reports by Choi and Zmistowski for PJI cases (18% at 4 years and 26% at 5 years respectively) (10,35).

DAIR in unicompartmental knee arthroplasty (UKA)

In comparison to DAIR for TKA there is a scarcity of evidence published specifically regards DAIR for UKA. This may be explained in part due to lower numbers of UKAs implanted (~8% of knee replacements performed annually in the UK), and the lower revision for infection risk seen in primary UKA of (hazard ratio of 0.5 (95% CI: 0.38–0.66) compared to primary TKA) (36,37). A retrospective review of 15 UKA PJIs between 1992 and 2014 found a higher treatment success for two-stage revision (100% at 5 years) than for DAIR (61% at 5 years) (38). Retained cartilage in native compartments following UKA may present an additional mode of failure after DAIR, beyond infection recurrence. Chondrolysis after initial PJI, with progressive arthritis of native compartments, may necessitate additional surgery for symptom control (39). The ICM recommendation, in light of a lack of evidence, is that early DAIR can be considered, with one or two-stage revision (with conversion to TKA) used for treatment failure or in the setting of established infection (40).

Factors affecting outcome

Chronicity of DAIR

There are several variables recognised to influence the success of DAIR for infection control of PJI, with chronicity of infection one such factor. Specifically, the more chronic the duration of PJI, the less successful is DAIR. Kunutsor et al.’s meta-analysis reported infection control of 67.7% (95% CI: 68.9–81.5%) for acute postoperative infection, and 52.7% (95% CI: 40.8–64.5%) for acute haematogenous infection, falling to 31.9% (95% CI: 8.5–60.2%) in late chronic PJI (Table 4) (18). A similar pattern was demonstrated in subgroup analyses exploring time from primary implantation to symptom onset, duration of symptoms before DAIR and time from index primary implantation to DAIR (shorter windows demonstrated better success). It should be noted that these figures include DAIR outcomes of different joints, with the same meta-analysis demonstrating lower success rates for knee DAIR compared to hip, shoulder and elbow. However, Ottesen et al. reported that DAIR within 90 days of primary implantation had treatment success of 90% vs. 60% for those revised with DAIR beyond 90 days (41). Narayan et al. similarly found that patients undergoing DAIR sooner after index TKA (≤2 vs. >2 weeks) had greater treatment success (23). Qu et al. demonstrated that a symptom period of >3 weeks resulted in reduced DAIR success rates for knee PJI (20). The lower success for infection eradication associated with the duration of infection is likely related to the development of a mature biofilm on prosthetic surfaces. Both the mature biofilm, and the metabolic changes of bacteria within in the biofilm, demonstrate resistance mechanisms to host defences and antibiotics. Classically these time windows have been described as acute post-operative (≤3–6 weeks after primary implantation), acute haematogenous (any time after the acute post-operative period and with a short symptom history) or chronic. Acute post-operative PJI is likely secondary to operative contamination, whereas acute haematogenous results from seeding of bacteria from other sites. Whilst useful as a clinical guide, there are recent suggestions to move away from such a classification, given greater understanding of biofilm formation (42).

Causative organism and DAIR outcome

The causative organism is also an important factor influencing the likely success of DAIR. Broadly, those organisms with broader antimicrobial resistance profiles will be more difficult to eradicate, as are those able to rapidly produce biofilms or with multiple defences against host immune responses. The majority of PJI are caused by Gram-positive cocci, in particular Staphylococcus aureus, and coagulase negative Staphylococci (CoNS). Polymicrobial infection is also found in a significant proportion of knee PJI. Other common organisms include Streptococci, Enterococci, aerobic Gram-negative bacilli and anaerobic bacteria. Within the literature a wide range of other bacterial species have been identified as causative organisms in PJI. Kunutor et al. have demonstrated the influence of organism on DAIR success, with Staph. aureus associated with a slightly lower success of infection eradication (56.5%, 95% CI: 41.7–70.7), compared to other Gram-positive and Gram-negative organisms (Table 5) (18). Iza et al. recently reported a similar finding, with Staph. aureus being associated with poorer treatment success vs. non-Staph. aureus species (21). Fungal PJI is thankfully rare, and is mainly seen in hosts who are otherwise immunocompromised. DAIR is not appropriate in these settings, and two-stage revision should be considered. Finally, ‘culture negative’ PJI represents the scenario with a clinically infected prosthesis, but where no organisms are identified on culture. This can be a result of failure to sample, difficult to culture organisms or administration of antibiotics prior to sampling (43,44). New molecular tools for culture-negative PJI diagnosis are being actively investigated (45).

Host factors and DAIR outcome

Host factors are believed to influence the likelihood of success after DAIR. The McPherson staging system considers systemic features (such as immunocompromise, advanced age and malnutrition) and local limb features (such as poor soft tissue envelope and vascular insufficiency) in an effort to identify patients who are at risk of a poor outcome. Bryan et al. demonstrated that healthy patients (McPherson Grade A) had a lower treatment failure rate than unhealthy patients (McPherson Grade C), at 8% vs. 44% over a median follow-up of 6 years, for DAIR in the setting of acute hip PJI (46).

Technical aspects of DAIR and outcome

The technical aspects of DAIR surgical technique have been described elsewhere in this issue, but there is evidence that the method of DAIR has an influence on treatment success. Byren et al. found a significantly higher risk of treatment failure in a retrospective cohort of 112 mixed joint DAIRs, with a hazard ratio of 4.2 (95% CI: 1.5–12.5) for arthroscopic vs. open DAIR (47). The recent International Consensus Meeting found a strong majority and consensus against the role of arthroscopy in management of PJI (40).

Where possible it is recommended that modular components are exchanged, with evidence supporting improved treatment success where this is done (40). This intuitively makes sense as removal of a modular polyethylene bearing not only results in the reduction of the bioburden, but it also allows access to the posterior capsule of the knee joint for debridement. From a general DAIR perspective Lora-Tamayo et al. demonstrated higher treatment failure of DAIR when component exchange was not performed in a multi-centre review of 349 hip and knee PJIs (48). Choi et al. reported a significant benefit of polyethylene exchange in knee DAIR, with a 52.6% success rate vs. 0% without exchange (49).

Closing statements

DAIR is a viable option in managing acute PJI following knee arthroplasty and there is growing interest in identifying cases amenable to DAIR with a high chance of treatment success. The advantage of this technique in comparison to formal staged revision surgery is the reduced morbidity and better functional outcomes. The evidence base largely consists of small cohort studies (often retrospective), rather than randomised controlled trials. Meta-analyses have been undertaken to improve outcome estimates, but heterogeneity in diagnostic criteria, causative organisms, surgical technique, antibiotic regimens and definitions of treatment/failure success are limitations. The key points in achieving a positive outcome after DAIR for PJI are largely agreed to be a short clinical duration of infection, exchange of modular components (where possible), an organism with antibiotic sensitivities, and an uncompromised host. Publications over the last 20 years reporting the outcome of DAIR for acute PJI typically report treatment success rates of ~50–70%, within the limitations detailed above. Functional outcomes appear generally good compared to formal revision surgery, but few studies report these. Improving consensus regarding diagnosis, organisms, treatment and outcome definitions will allow greater comparisons in future work, and more robust pooling of data across centres for meta-analysis.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the Guest Editors (Nemandra A. Sandiford, Massimo Francescini and Daniel Kendoff) for the series “Prosthetic Joint Infection” published in Annals of Joint. The article has undergone external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/aoj-20-76). The series “Prosthetic Joint Infection” was commissioned by the editorial office without any funding or sponsorship. AP serves as an unpaid editorial board member of Annals of Joint from July 2019 to June 2021. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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