Periprosthetic joint infection (PJI) is a devastating complication after total knee arthroplasty (TKA), and the results observed after PJI treatment are inferior to those experienced by patients who do not require revision.1 As the number of primary TKAs has continued to increase, the incidence of PJI also has increased; studies have reported the rate of PJI to vary from 1% to 4%.2
The 2 most common surgical procedures are 1- and 2-stage revisions. One-stage revisions, based on the immediate placement of a definitive prosthesis, are reserved for when the infecting organism has been identified and effective antibiotics are available. This can be the preferential method for treating infection with a single organism or one of low virulence. In contrast, 2-stage exchange arthroplasty usually is performed in patients with systemic manifestations of infection, a sinus tract, or poor soft tissue coverage; when no organism has been identified; or when the infecting organisms are resistant to antibiotics.3
A meta-analysis by Kunutsor et al4 defined patient-related risk factors for PJI after total joint arthroplasty. History of diabetes, rheumatoid arthritis (RA), depression, steroid use, and smoking; male sex; body mass index greater than 30 kg/m2; and previous joint surgery are associated with increased risk of PJI. Rheumatoid arthritis and other inflammatory joint diseases, treatment related to immunosuppression, and baseline inflammatory changes can complicate the prevention, diagnosis, and treatment of PJI.5 However, there is a lack of information regarding whether RA is a risk factor for failure of revision TKA due to PJI and whether RA patients have different results than non-RA patients. This study evaluates the success and failure rates as well as the final results after 2-stage revision TKA, with particular emphasis placed on comparing RA and non-RA patients.
Materials and Methods
This study was performed on the basis of a prospectively collected database that comprised 143 consecutive patients (143 knees) treated for PJI with 2-stage revision TKA. All primary TKA procedures were performed between 1996 and 2014. First revisions were performed from 2007 to 2015 at the first author's institution.
The following criteria were used for inclusion in the study: (1) a previous TKA procedure, (2) a diagnosis of infection based on the International Consensus Group (ICG) criteria,3 and (3) informed consent for participation in the study. Three of the 143 patients were excluded from the study: 2 did not attend for the ambulatory visit, and 1 underwent a second-stage operation in another hospital. After the exclusion process, 140 knees (patients) were analyzed.
The mean period from second-stage revision to final follow-up was 53.3 months (range, 26 to 127 months). Patients were divided into 2 groups: a study group consisting of 15 patients (RA group) and a control group of 125 patients without RA (non-RA group). Both groups of patients had been treated at the same medical center with the same protocol. The procedures were performed by 5 different surgeons. None of the non-RA patients had received immunosuppressive or corticosteroid therapy. All of the RA patients had received immunosuppressive or corticosteroid therapy, or both.
The administration of any biological disease-modifying antirheumatic drugs for RA treatment was stopped 6 weeks before surgery and was resumed after second-stage revision TKA for 6 weeks. Anti-inflammatory medication and steroid therapy were continued throughout the orthopedic treatment. Methotrexate was ended 1 week before surgery and resumed after the operation. Patient demographic and clinical data are summarized in Table 1.
Patient Demographics and Clinical Data
The decision to perform revision surgery was made on the basis of the clinical examination, the presence of a sinus tract communicating with the joint, radiographic imaging, positive periprosthetic or sinus tract cultures, and levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Cultures were grown for 14 days to identify microorganisms. Starting in 2012, sonication of the removed implant and spacer was used (23 cases). The Synovasure Alpha Defensin Test (Zimmer Biomet, Warsaw, Indiana) was used in 3 cases to identify the infection.
Two-stage revision was the standard treatment for all patients at the current authors' institution, with no patient undergoing a single-stage revision. The crucial argument for choosing this strategy during the study time interval was based on significantly higher rates of negative cultures in previous years. During the first stage, the knee was approached, and between 3 and 6 tissue and fluid samples were obtained for analysis. Any sinus was excised, followed by wide debridement of infected material and the excision of all necrotic, contaminated, or friable tissue. The old implants were removed. Infected tissues, including bone cement if necessary, were debrided, and irrigation then was performed with copious quantities of normal saline and Betadine (Avrio Health LP, Stamford, Connecticut). Finally, a custom-made knee spacer (Tecres, Verona, Italy) was implanted with the use of gentamicin-loaded bone cement. The suction drain was left in place until the second day after the operation or for as long as wound secretion was present.
No puncture of the knee was performed in the period between the first- and second-stage procedures. Second-stage revision was performed after a minimum period of 2 to 3 months if the following conditions were met: no clinical signs of infection were observed, CRP level was below 10 mg/dL, and white blood cell count and ESR were within normal ranges (<12,000/mL and <30 mm/h, respectively). During the second-stage operation, the spacer was removed, and pulse-lavage and washout was performed using Betadine. In some patients, the spacer remained for a longer time than initially planned, for reasons independent of the surgeon.
Both groups received the same postoperative care. The drains were removed on the second postoperative day. Intravenous antibiotics were administered for 1 week, and then oral antibiotics were prescribed for 6 weeks according to an antibiogram or empirical information if the cultures were negative. After 8 weeks of clinical examination, CRP and ESR levels were obtained, with the CRP level repeated until normalization. All patients were evaluated radiographically at 6-month intervals with standard anteroposterior and lateral knee radiographs in a standing position. In 38 patients, normal CRP levels were not achieved, and recurrence of infection was observed.
The results were assessed according to Diaz-Ledezma et al,6 who defined the success of PJI treatment as: (1) eradication of infection, characterized by a healed wound without fistula, drainage, or pain, and no recurrence of infection caused by the same strain of organism; (2) no subsequent surgical intervention required for infection after reimplantation surgery; and (3) no occurrence of PJI-related mortality. A follow-up of 2 years after the definitive PJI surgery was defined as the short-term result.6 Radiographic analysis used the Knee Society Roentgenographic Evaluation and Scoring System to assess the quality of component fixation.7 The Knee Society Clinical Rating System (KSS) was used for clinical assessment.8
Due to frequently elevated inflammatory markers (CRP level >10 mg/dL) and cell count in synovial fluid in RA, diagnosis of PJI in negative cultures was made based on clinical symptoms (sinus tract to the joint as a major criteria, joint pain, swelling, redness, and elevated skin temperature), radiographic signs of loosening, significantly higher CRP level compared with recent examinations, purulent synovial fluid, or positive alpha defensin test. The absence of these factors following spacer implantation and systemic antibiotic therapy in this group was accepted as a treatment success and was considered a key point before the final revision.
Program Statistica 13 (Tibco Software Inc, Palo Alto, California) was used for statistical analysis. Fisher's exact test was applied to calculate the significance of the difference between RA and non-RA patients with regard to results of treatment, evaluated according to Diaz-Ledezma et al,6 bacteria detection rate, and sex. The Levene test was used to assess the normality of distribution. The t test for independent samples was used to compare the results of the first and second revisions between groups, and the Mann–Whitney U test was used to compare the RA and non-RA patients with regard to KSS and age. For all analyses, the level of significance was set as P=.05.
Recurrence of infection after the first 2-stage revision was observed in 38 (27.1%) patients. This group included 4 (26.7%) RA patients and 34 (27.2%) non-RA patients. Eight (21%) of these patients underwent a successful second 2-stage revision procedure. Twenty-seven (71.1%) patients were not considered to be acceptable candidates for a second 2-stage revision and underwent either arthrodesis (25 patients) or amputation (2 patients). Three (7.9%) patients either refused further treatment or were lost to follow-up. No recurrence of infection was noted after knee arthrodesis or amputation.
The types of bacteria identified during the first 2-stage TKA are listed in Table 2. In 55 cases, no bacteria were identified; the detection rate was 39.3% for the entire analyzed population. More than 1 strain of bacteria was found in 8 knees, and 1 pathogen was identified in the remaining 77 knees.
Comparison of Patients With and Without RA Treated for PJI With Two-Stage Revision TKA
The composition of the RA and non-RA groups was comparable in terms of sex (Table 2); however, mean age of the RA group was younger than in the non-RA group: 60.5 vs 67 years (P=.002). No statistically significant difference was observed between the 2 groups in terms of success or failure rate according to the Diaz-Ledezma criteria (P=.6) or KSS (P=.3). However, the detection rate was significantly higher in the non-RA group than in the RA group (P=.005) (Table 2).
The results of revision TKA for PJI are well documented in the literature, with success rates ranging from 72% to 100%.9–13 The findings of the current study regarding 2-stage TKA for chronic PJI are consistent with those reported in the literature.9–13 However, the results are difficult to compare among studies because different criteria were used to define success. Moreover, most studies did not differentiate between knee and hip revisions when reporting their results, and many studies used different management protocols.
Janssen et al9 reported that 18 of 25 patients underwent reimplantation in the course of 2-stage septic revision TKA. Of the 18 patients with reimplantation, 17 healed and 1 did not. The remaining 7 patients required knee arthrodesis (5 patients) and amputation (2 patients). Haddad et al10 observed only 2 reinfections among 74 patients following 2-stage revision knee arthroplasty; the authors reported a 100% success rate for single-stage revision TKA among 28 patients using a highly selective single-stage revision approach. The best results, with 100% of infections reported as being resolved in 2-stage revision TKA, were presented by Parkinson et al.11 Haleem et al12 reported 93.5% survivorship free of implant removal for reinfection at 5 years and 85% at 10 years. In 96 patients who underwent 2-stage reimplantation for treatment of an infected TKA, 9 knees required implant removal for reinfection.
In the current study, only 3 patients demonstrated recurrence of infection after final treatment. However, recurrence of infection after revision TKA was found in 38 of 140 patients. Among the 38 patients with recurrence, 25 required knee arthrodesis, 2 required amputation, and 8 were treated successfully with another 2-stage revision TKA.
In the current study, long-term treatment between the first- and second-stage TKA was implemented in most cases. This approach gives the greatest chance that the infection will be resolved prior to reimplantation, and it also eases the second stage by allowing spacers to be used to improve function during the long discharge period and to facilitate reimplantation. This approach allows systemic antibiotic therapy to be completed, and the result of treatment can be observed in an antibiotic-free period. Although similar preferences have been reported by others,9,14 some authors prefer a shorter period of spacer use.3,10,15
The most interesting part of the current study is the comparison of RA and non-RA patients. Surprisingly, no significant difference was found between these 2 groups in terms of KSS or the success and failure rates. Although no similar studies have examined TKA revision for PJI in patients with RA, data obtained from a study of a Danish registry indicate RA patients had a lower 10-year risk of revision than osteoarthritis (OA) patients following primary hip and knee replacement, but a greater risk of death and PJI.16 Cordtz et al16 attributed the lower rate of revision to decreased wear of the implant associated with the lower physical activity in RA patients compared with OA patients, and to surgeons possibly being less prone to perform revisions on RA patients due to comorbidities and fragile bone stocks.
Similar conclusions were reached by Ravi et al17 in a meta-analysis; they reported a higher risk of infection following TKA but a similar revision rate after 5 and 10 years. The increased risk of infection observed in RA patients may be attributable to an impaired immune system response brought about by the disease itself or by its immunosuppressive treatment. Stundner et al18 found the mortality rates and most major perioperative adverse events were similar in the 2 groups (OA and RA), with the exception of infection.
Regarding the high sensitivity and specificity of the Synovasure Alpha Defensin Test, the current authors agree with Parvizi et al,19 who have proposed new evidence-based, validated criteria and emphasized the high value of this test in the detection of PJI in negative-culture cases and in the absence of a sinus tract to the joint. This test may increase the detection rate and complements thoroughly other infection markers and recent ICG minor criteria, especially in suspected cases of PJI with clinical symptoms and a slightly elevated CRP level, or in cases with the coexistence of systemic inflammatory diseases such as RA.19
The current study has several limitations. First, although the study is retrospective, it is based on data that were collected prospectively. Second, the 2 analyzed groups are difficult to compare from a functional point of view; however, the results were compared on the basis of knee score rather than functional score, as the latter is influenced by other comorbidities such as pathologies of the large joints or spine. Third, although a minimum follow-up of 2 years is not sufficient to conclusively establish that these patients will remain without infection, Diaz-Ledezma et al6 defined this follow-up as a short period. All patients will undergo follow-up in case of an infection. Fourth, the risk of infection after TKA can be influenced by a number of risk factors, including age, sex, time from operation, duration of symptoms, patient comorbidities, and the pathogen causing the infection,13 and patients display great heterogeneity regarding comorbidities, particularly non-RA patients. The number of subgroups would be too small to perform a multivariate analysis to further investigate the effect of all of these risk factors on infection control outcome. Finally, the RA group of 15 patients is significantly smaller than the control group of 125 patients, which makes comparison difficult; however, adequate statistical tests were used to compare statistical differences. In conclusion, RA and non-RA patients demonstrated similar reinfection rates and final results after revision TKA for PJI.
- Marczak D, Synder M, Sibinski M, Okon T, Kowalczewski J. The use of calcium carbonate beads containing gentamicin in the second stage septic revision of total knee arthroplasty reduces reinfection rate. Knee. 2016;23(2):322–326. doi:10.1016/j.knee.2015.12.001 [CrossRef]
- Alijanipour P, Bakhshi H, Parvizi J. Diagnosis of periprosthetic joint infection: the threshold for serological markers. Clin Orthop Relat Res. 2013;471(10):3186–3195. doi:10.1007/s11999-013-3070-z [CrossRef]
- Parvizi J, Gehrke T, Chen AF. Proceedings of the International Consensus on Peri-prosthetic Joint Infection. Bone Joint J. 2013;95B(11):1450–1452. doi:10.1302/0301-620X.95B11.33135 [CrossRef]
- Kunutsor SK, Whitehouse MR, Blom AW, Beswick ADINFORM Team. Patient-related risk factors for periprosthetic joint infection after total joint arthroplasty: a systematic review and meta-analysis. PLoS One. 2016;11(3):e0150866. doi:10.1371/journal.pone.0150866 [CrossRef]
- Morrison TA, Figgie M, Miller AO, Goodman SM. Periprosthetic joint infection in patients with inflammatory joint disease: a review of risk factors and current approaches to diagnosis and management. HSS J. 2013;9(2):183–194. doi:10.1007/s11420-013-9338-8 [CrossRef]
- Diaz-Ledezma C, Higuera CA, Parvizi J. Success after treatment of periprosthetic joint infection: a Delphi-based international multidisciplinary consensus. Clin Orthop Relat Res. 2013;471(7):2374–2382. doi:10.1007/s11999-013-2866-1 [CrossRef]
- Ewald FC. The Knee Society total knee arthroplasty roentgenographic evaluation and scoring system. Clin Orthop Relat Res. 1989;(248):9–12.
- Insall JN, Dorr LD, Scott RD, Scott WN. Rationale of the Knee Society clinical rating system. Clin Orthop Relat Res. 1989;(248):13–14.
- Janssen DM, Geurts JA, Jütten LM, Walenkamp GH. 2-stage revision of 120 deep infected hip and knee prostheses using gentamicin-PMMA beads. Acta Orthop. 2016;87(4):324–332. doi:10.3109/17453674.2016.1142305 [CrossRef]
- Haddad FS, Sukeik M, Alazzawi S. Is single-stage revision according to a strict protocol effective in treatment of chronic knee arthroplasty infections?Clin Orthop Relat Res. 2015;473(1):8–14. doi:10.1007/s11999-014-3721-8 [CrossRef]
- Parkinson RW, Kay PR, Rawal A. A case for one-stage revision in infected total knee arthroplasty?Knee. 2011;18(1):1–4. doi:10.1016/j.knee.2010.04.008 [CrossRef]
- Haleem AA, Berry DJ, Hanssen AD. Mid-term to long-term followup of two-stage reimplantation for infected total knee arthroplasty. Clin Orthop Relat Res. 2004;(428):35–39. doi:10.1097/01.blo.0000147713.64235.73 [CrossRef]
- Vanhegan IS, Morgan-Jones R, Barrett DS, Haddad FS. Developing a strategy to treat established infection in total knee replacement: a review of the latest evidence and clinical practice. J Bone Joint Surg Br. 2012;94(7):875–881. doi:10.1302/0301-620X.94B7.28710 [CrossRef]
- Leonard HA, Liddle AD, Burke O, Murray DW, Pandit H. Single- or two-stage revision for infected total hip arthroplasty? A systematic review of the literature. Clin Orthop Relat Res. 2014;472(3):1036–1042. doi:10.1007/s11999-013-3294-y [CrossRef]
- Marczak D, Synder M, Sibinski M, Polguj M, Dudka J, Kowalczewski J. Two stage revision hip arthroplasty in periprosthetic joint infection. Comparison study: with or without the use of a spacer. Int Orthop. 2017;41(11):2253–2258. doi:10.1007/s00264-017-3500-8 [CrossRef]
- Cordtz RL, Zobbe K, Højgaard P, et al. Predictors of revision, prosthetic joint infection and mortality following total hip or total knee arthroplasty in patients with rheumatoid arthritis: a nationwide cohort study using Danish healthcare registers. Ann Rheum Dis. 2018;77(2):281–288. doi:10.1136/annrheumdis-2017-212339 [CrossRef]
- Ravi B, Escott B, Shah PS, et al. A systematic review and meta-analysis comparing complications following total joint arthroplasty for rheumatoid arthritis versus for osteoarthritis. Arthritis Rheum. 2012;64(12):3839–3849. doi:10.1002/art.37690 [CrossRef]
- Stundner O, Danninger T, Chiu YL, et al. Rheumatoid arthritis vs osteoarthritis in patients receiving total knee arthroplasty: perioperative outcomes. J Arthroplasty. 2014;29(2):308–313. doi:10.1016/j.arth.2013.05.008 [CrossRef]
- Parvizi J, Tan TL, Goswami K, et al. The 2018 definition of periprosthetic hip and knee infection: an evidence-based and validated criteria. J Arthroplasty. 2018;33(5):1309–1314. doi:10.1016/j.arth.2018.02.078 [CrossRef]
Patient Demographics and Clinical Data
|Age at primary TKA, mean (range), y||66.2 (34–88)|
|Age at first revision TKA, mean (range), y||67.9 (43–89)|
|Left/right knee, No.||59/81|
|Duration of first spacer, mean (range), mo||8.2 (2–24)|
|Duration of second spacer, mean (range), moa||9.8 (2–26)|
|Duration of third spacer, mob||2 and 7|
| First revision TKA successful||102|
| Recurrence of infection||3|
| Second septic revision (spacer+TKA)||8|
Comparison of Patients With and Without RA Treated for PJI With Two-Stage Revision TKA
|Age, mean (range), y||67 (29–87)||60.5 (24–83)||.002a|
|Duration of spacer, mean, mo||8.1||9.1||.5|
|KSS, mean (range), points||75.0 (37–95)||74.1 (39–90)||.3|
Staphylococcus epidermidis MSCNS||4|
Staphylococcus epidermidis MRCNS||6|
Streptococcus group F||1|
Streptococcus group G||1|
Streptococcus group B||1|
Staphylococcus haemolyticus MRCNS||1|
Streptococcus group C||1|
| 2 bacteria||8|