What Are the Treatment Options for TKA Patients with a PJI?
Dr. Bryan Springer answers questions from ICJR about managing a total knee arthroplasty patient who has a deep periprosthetic joint infection, in part 2 of a 2-part series. Part 1 was published yesterday.
ICJR: What are the options for managing total knee arthroplasty patients diagnosed with a periprosthetic joint infection (PJI)?
Bryan D. Springer, MD: The treatment options for these patients include:
- Retention of the prosthesis with antibiotic suppression
- Open irrigation and débridement with polyethylene exchange
- Prosthesis removal, which can involve:
- Resection arthroplasty
- Single-stage exchange arthroplasty
- 2-stage exchange arthroplasty
In the classification system for infected total joints by Tsukayama et al: 
- A type I infection involves a patient with a positive culture at the time of surgery.
- A type II infection is an early infection that occurs within the first 4 weeks after surgery.
- A type III infection is a late, acute, hematogenous infection that occurs after the TKA, with symptoms of less than 4 weeks’ duration.
- A type IV infection is a late, chronic infection with symptoms that have persisted for more than 4 weeks.
Antibiotic suppression is recommended only in patients who are medically debilitated and unable to undergo surgery. The infectious agent should have a low virulence and the patient should:
- Be in stable condition
- Have well-fixed components
- Be able to be treated with a suitable oral antibiotic agent
The literature suggests that the success rate of antibiotic suppression is approximately 20%. [2,3]
The application of this strategy to patients beyond this strict definition may result in harmful delay in more definitive treatment.
Irrigation and Débridement
Irrigation and débridement is viewed by surgeons and patients as an attractive, low-morbidity option to treat an acutely infected joint.
The success of this procedure, however, has come under scrutiny in the literature over the past several years.
Historically, open irrigation and débridement for an infected TKA was reserved for patients with an acute onset of infection, as irrigation, débridement, and component retention for treatment of a chronic infection (signs and symptoms for more than 4 weeks) had been associated with high failure rates and poor outcomes. [4,5]
The results of treatment with open irrigation and débridement have been quite variable and when viewed as a whole, probably much more sobering that most surgeons would anticipate. Based on our evaluation of more than 20 published articles, the success rate of this procedure ranges from 19% to 83%, with most studies reporting success rates less than 60%.
A 2002 meta-analysis by Silva et al  evaluated 530 patients treated with open irrigation and débridement for an acute PJI. This study included acute postoperative infections and late acute hematogenous infections. The overall success was 33.6%.
The wide range of success and failure suggests that numerous variables affect outcomes of irrigation and débridement, including:
- Timing of surgery
- Patient risk factors
- Surgical technique
- Infecting organism
Timing of surgery had been thought to be the most important factor in the success of irrigation and débridement and polyethylene exchange, but that may not be the case. Several studies have reported that the time from onset of symptoms (less than 4 weeks) to surgical irrigation and débridement was not a factor in the outcome. Instead, most authors have shown improved success when treatment is initiated following a shorter duration of symptoms. [7-9]
The attraction of irrigation and débridement is that it is a simple procedure all surgeons can perform without specialized instruments or techniques. Additionally, the thought is that if irrigation and débridement fails, the surgeon can them simply perform a 2-stage exchange arthroplasty, and thus little is lost by attempting an open irrigation and debridement.
Recent literature, however, refutes this assumption. Sherell et al  reported a 34% failure rate for 2-stage exchange arthroplasty in patients who had previously undergone open irrigation and débridement to treat an acute infection. This is substantially higher than the failure rate reported for a 1-stage exchange alone.
Infections with resistant organisms are on the rise and, in fact, are already a leading cause of PJI in many centers. A methicillin-resistant Staphylococcus aureus (MRSA) infection poses a particular challenge because of its virulent nature and the limited options for antibiotic therapy.
Bradbury et al  reported on 19 acute periprosthetic MRSA infections treated with open irrigation, débridement, and component retention. At a minimum 2-year follow-up, the failure rate was 84%.
They also reported on 34 studies in the current literature in which 13 patients were identified with an acute MRSA infection and treated with open irrigation, débridement, and component retention. The reported failure rate for those patients was 77%. 
Based on these finding, we believe there is a very limited role for open irrigation and débridement in the face of resistant organisms, regardless of the timing or onset of the infection. At our institution, we now favor a 2-stage exchange arthroplasty for the treatment of all types of infections associated with MRSA and resistant organisms following total knee arthroplasty.
Although it is understood that open irrigation and débridement for virulent organisms has a higher failure rate, even more concerning is recent literature suggesting that the failure rate for irrigation and débridement is high regardless of the timing or the infecting organisms. This calls into question the validity of the procedure itself, even for low-virulence organisms.
Koyonos et al  retrospectively reviewed the records of 136 patients (138 joints) treated with irrigation and débridement between 1996 and 2007 at 2 institutions. Three subgroups were extracted:
- Acute postoperative infections, occurring within 4 weeks (52 joints)
- Acute delayed infections, occurring after 4 weeks with acute onset of symptoms (50 joints)
- Chronic infections (36 joints)
Minimum follow up was 12 months (average, 54 months; range, 12 to 115 months). Infection control was not achieved in 90 joints. Failure rates were 69% (36/52), 56% (28/50), and 72% (26/36) for acute postoperative, acute delayed, and chronic infections, respectively. 
The authors concluded that irrigation and débridement is unlikely to control PJI, including acute infections, and they recommend caution in adopting this procedure as a routine means to address PJI. 
Odum et al  performed a multicenter, retrospective cohort study of 200 consecutive PJIs treated with open irrigation and débridement. Failure was defined as reoperation for infection. The authors found that:
- The failure rate for streptococcal infections was 65% (20/31), compared with 71% (84/119) for other organisms.
- The failure rate for sensitive Staphylococcus organisms was 72% (48/67), compared with a 76% (22/29) failure rate for resistant Staphylococcus
These results indicate that eradication rates of irrigation and débridement for a streptococcal PJI are comparable with other causative organisms. The authors concluded that irrigation and débridement should play a limited role in the treatment algorithm regardless of organism type. 
Single-stage Exchange Arthroplasty
Single-stage exchange arthroplasty involves the removal of all components and the reinsertion of another prosthesis in the same surgery. Although this is an attractive option, the literature is limited to studies with small numbers of patients.
The 2 largest published series involve only 22 and 18 patients, respectively. [14,15] Although these authors report a success rate ranging from 89% to 91%, it is important to keep in mind that only an optimal host may be appropriate candidate, and surgeons should choose this procedure with extreme caution in today’s era of drug-resistant organisms.
Because of the limited data, we do not perform single-stage exchange arthroplasty for treatment infected total knee arthroplasties. Although there are benefits to a single-stage exchange for patients and the healthcare system, failure can be associated with significant morbidity.
2-stage Exchange Arthroplasty
Two-stage exchange arthroplasty is considered the gold standard for the treatment of a chronic PJI. The procedure involves the removal of the infected prosthesis and thorough debridement to remove any necrotic and foreign material, including all cement. A high-dose antibiotic cement spacer is placed at the time of the initial surgery and the patient is treated with a course of intravenous antibiotics tailored to the infecting organism.
Treatment variables include:
- The amount and type of antibiotics to be used in the spacer
- The type of spacer, mobile versus articulating
- The length of intravenous antibiotic therapy
- The time between resection and reimplantation
Amount and Type of Antibiotics
The amount and type of antibiotics in the spacer remains controversial. In general, a high-dose antibiotic spacer is defined as having between 2 grams and 8 grams of antibiotic per batch of cement. The most commonly available powdered, heat-stable antibiotics are vancomycin, gentamicin, and tobramycin.
It is important to remember that different cements elute antibiotics differently. Higher doses of antibiotics increase the porosity of the cement, which allows for greater cement elution and higher antibiotic levels locally than can be achieved with intravenous administration.  Although there are a few case reports of systemic toxicity from antibiotics in cement, high local concentrations of antibiotics in cement are generally well tolerated, with minimal systemic risks. [17,18]
At our institution, we currently use a high-viscosity cement and add 2 grams of vancomycin and 2.4 gram of tobramycin per 40-gram pack of cement.
Static vs Articulating Spacers
Two general categories of antibiotic spacer are described in the literature, static and articulating.
Static spacers preserve the joint space and minimize the generation of cement debris, but they do not allow motion during the interval period.
- Static preformed blocks have been associated with increased bone loss, migration, and extensor mechanism necrosis and generally should be avoided.
- A molded static spacer, in which the cement is placed in a doughy state to allow the cement to mold to the bony surfaces, can prevent many of the problems associated with a preformed block spacer.
Several types of articulating spacers are available. Articulating spacers:
- Maintain soft-tissue pliability
- Can reduce bone loss
- Can facilitate range of motion
- Allow for improved patient mobility
- Facilitate easier exposure at the time of revision surgery
Regardless of the type of spacer used, an important technical point involves accessing and debriding the intramedullary canals of the femur and the tibia with placement of antibiotic dowels into the canal.  Data have shown that infection exists in the intramedullary canals in up to one third of patients with an infected total knee arthroplasty. 
Conclusive results showing the advantage of articulating spacers over static spacers are limited. Emerson  demonstrated no difference in infection rates when comparing 26 static spacers with 22 articulating spacers at 36 months. The articulating spacer group, however, did show improved overall range of motion than the group with a static spacer at final follow-up.
In a study evaluating static versus articulating spacers, Freeman et al  reported a comparable infection eradication rate. However, patients with the articulating spacers had better functional results than patients with static spacers.
At our institution, we currently use static and articulating spacers, depending on several host factors, mainly bone loss.
- In patients with well-preserved distal femoral and proximal tibial bone, we use an articulating spacer. This allows the patient to be partial weight-bearing and provides for range of motion as tolerated during the interim period.
- In patients with severe distal femoral or proximal tibial bone loss that compromises collateral ligament integrity, our preference is to use a static spacer. We have concerns about the stability of an articulating spacer with motion in these patients.
Length of Intravenous Antibiotic Therapy
The optimal duration of intravenous antibiotics following resection arthroplasty and the amount of time off antibiotics prior to reimplantation have not been clearly defined. In general, a 6-week course of intravenous antibiotics is administered, followed by a 4- to 6-week period off antibiotics, during which patients are evaluated clinically.
Prior to reimplantation, patients should be evaluated for the presence of persistent infection. Clinical and serologic examinations are performed to evaluate eradication of infection. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are generally useful tools in evaluating the effect of treatment prior to reimplantation.
However, these serologic markers may not return to normal prior to reimplantation. In a study by Kusuma et al,  the ESR and the CRP remained elevated in 54% and 21% of patients, respectively, who were proven to be free of infection at time of the reimplantation. The authors were unable to identify an optimum cut off value for either ESR or CRP prior to reimplantation.
More important than absolute values, a trend toward normalization of the values over the treatment period may be most indicative of response to treatment.
Aspiration prior to reimplantation may be the most useful tool for evaluating the presence of persistent infection. However, a strict cell count and differential has yet to be elucidated to guide treatment.
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- Rasul AT, Jr., Tsukayama D, Gustilo RB. Effect of time of onset and depth of infection on the outcome of total knee arthroplasty infections. Clinical Orthopaedics & Related Research. Dec 1991(273):98-104.
- Schoifet SD, Morrey BF. Treatment of infection after total knee arthroplasty by debridement with retention of the components. Journal of Bone & Joint Surgery – American Volume. Oct 1990;72(9):1383-1390.
- Silva M, Tharani R, Schmalzried TP. Results of direct exchange or debridement of the infected total knee arthroplasty. Clinical Orthopaedics & Related Research. Nov 2002(404):125-131.
- Brandt CM, Sistrunk WW, Duffy MC, et al. Staphylococcus aureus prosthetic joint infection treated with debridement and prosthesis retention. Clinical Infectious Diseases. May 1997;24(5):914-919.
- Hsieh P-H, Lee MS, Hsu K-Y, Chang Y-H, Shih H-N, Ueng SW. Gram-negative prosthetic joint infections: risk factors and outcome of treatment. Clinical Infectious Diseases. Oct 1 2009;49(7):1036-1043.
- Marculescu CE, Berbari EF, Hanssen AD, et al. Outcome of prosthetic joint infections treated with debridement and retention of components. Clinical Infectious Diseases. Feb 15 2006;42(4):471-478.
- Sherrell JC, Fehring TK, Odum S, et al. The Chitranjan Ranawat Award: fate of two-stage reimplantation after failed irrigation and debridement for periprosthetic knee infection. Clinical Orthopaedics & Related Research. Jan 2011;469(1):18-25.
- Bradbury T, Fehring TK, Taunton M, et al. The fate of acute methicillin-resistant Staphylococcus aureus periprosthetic knee infections treated by open debridement and retention of components. Journal of Arthroplasty. Sep 2009;24(6 Suppl):101-104.
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- Dovas S, Liakopoulos V, Papatheodorou L, et al. Acute renal failure after antibiotic-impregnated bone cement treatment of an infected total knee arthroplasty. Clinical Nephrology. Mar 2008;69(3):207-212.
- Springer BD, Lee G-C, 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. Clinical Orthopaedics & Related Research. Oct 2004(427):47-51.
- Hanssen AD, Spangehl MJ. Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements. Clin Orthop Relat Res. 2004 Oct;(427):79-85.
- Mont MA WB, Hungerford DS. Evaluation of preoperative cultures before second-stage reimplantation of a total knee prosthesis complicated by infection. A comparison-group study. J Bone Joint Surg Am. Nov 2000;82-A(11):1552-1557.
- Emerson RH, Jr. Comparison of a static with a mobile spacer in total knee infection. Clin Orthop Relat Res. Nov 2002(404):132-138.
- Freeman MG, Fehring TK, Odum SM, Fehring K, Griffin WL, Mason JB. Functional advantage of articulating versus static spacers in 2-stage revision for total knee arthroplasty infection. Journal of Arthroplasty. Dec 2007;22(8):1116-1121.
- Kusuma SK, Ward J, Jacofsky M, Sporer SM, Della Valle CJ. What is the role of serological testing between stages of two-stage reconstruction of the infected prosthetic knee? Clinical Orthopaedics & Related Research. Apr 2011;469(4):1002-1008.
About the Expert
Bryan D. Springer, MD, is Fellowship Director at OrthoCarolina Hip and Knee Center, Charlotte, North Carolina.
Dr. Springer has no disclosures relevant to this article.