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Commentary and Perspective   |    
What Is the Role of Antibiotic-Containing Cement in Total Knee Arthroplasty?Commentary on articles by Robert S. Namba, MD, et al.: “Risk Factors Associated with Deep Surgical Site Infections After Primary Total Knee Arthroplasty. An Analysis of 56,216 Knees,” and Pedro Hinarejos, MD, PhD, et al.: “The Use of Erythromycin and Colistin-Loaded Cement in Total Knee Arthroplasty Does Not Reduce the Incidence of Infection. A Prospective Randomized Study in 3000 Knees”
Donald W. Roberts, MD1
1 Northwest Surgical Research Foundation, Vancouver, Washington
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The author received no payments or services, either directly or indirectly (i.e., via his institution), from a third party in support of any aspect of this work. Neither the author nor his institution has had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, the author has not had any other relationships, or engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.


Copyright © 2013 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2013 May 01;95(9):e62 1-2. doi: 10.2106/JBJS.M.00138
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Despite a prevalence of <1% in most series, periprosthetic joint infection is a devastating complication that is of major concern to patients, surgeons, and payers because of its attendant disability, difficult treatment, and cost. Risk factors leading to periprosthetic joint infection and methods of prevention are difficult to investigate because these infections are uncommon and large patient populations are necessary for sufficient statistical power to differentiate between treatment methods or to identify causative factors.
The May 1 issue of JBJS includes two important contributions toward understanding infection after total knee arthroplasty; however, both papers also demonstrate the problems attendant to investigating this clinical problem.
Risk Factors Associated with Deep Surgical Site Infections After Primary Total Knee Arthroplasty by Namba et al. is an observational study of prospectively collected data on 56,216 patients treated with primary total knee arthroplasty derived from the total joint replacement registry of the Kaiser Permanente health system. As has been reported in other studies, the authors showed that deep surgical site infection was associated with obesity, male sex, osteonecrosis, posttraumatic arthritis, and duration of surgery. The authors found that Hispanic race was protective against deep infection as was the use of antibiotic irrigation. Paradoxically, they also found that antibiotic-containing bone cement was significantly associated with an increased risk of infection.
Does antibiotic-containing bone cement actually increase the risk of infection? Antibiotic-containing cement was used in 12% of the cases, and presumably that cohort was heavily weighted toward cases that the surgeon thought had one or more risk factors for infection. Some of these risk factors may have been taken into account by the authors’ statistical model, but others may not have been. For instance, chronic urinary tract infection, chronic skin disease or infection, multiple previous knee operations, and a history of septic arthritis were not considered risk factors for the statistical analysis of this study. The surgeons may have taken those or other factors into account when determining who would benefit from antibiotic-containing cement, and the prevalence of infection in the patients who received antibiotic-containing cement may have been even higher had the antibiotic cement not been employed. This is the inherent problem of observational studies—it is difficult to account for all of the possible confounding variables.
The optimal alternative to an observational study is a randomized controlled trial, in which randomized assignment to treatment groups minimizes the possibility of confounding. The second paper, The Use of Erythromycin and Colistin-Loaded Cement in Total Knee Arthroplasty Does Not Reduce the Incidence of Infection, by Hinarejos et al. is a randomized study of the use of antibiotic-containing bone cement in 2948 patients over a five-year period. The rate of deep infection did not differ between the group treated with antibiotic cement (1.35%) and the control group (1.4%). Like Namba et al., these authors found that male sex and a longer surgical time were significantly associated with postoperative infection and that there was a trend toward higher infection rates in patients with diabetes and obesity. This study suggests that the use of antibiotic-containing bone cement does not decrease the rate of infection in the general population of patients undergoing primary total knee arthroplasty, at least with the antibiotics that the authors chose to investigate. One wishes that they had chosen tobramycin as the cement additive since that is the most common antibiotic used for this purpose. However, the authors should be recognized for the difficulty in conducting this study over five years to enroll enough patients and follow them long enough to attempt to detect a difference in the rates of a rare but important event. Future randomized studies of antibiotic-containing cement in primary knee arthroplasty should focus on the population of high-risk patients identified by these authors and others—i.e., patients treated with complex primary surgery with longer surgical times, obese patients, and patients with diabetes, osteonecrosis, or posttraumatic arthritis. A multicentered effort will be needed to enroll enough of these high-risk patients to adequately power the study.
Should one use antibiotic-containing cement in primary total knee arthroplasty? There is evidence from the Finnish total joint registry1 that antibiotic-containing cement lowers the risk of revision after knee arthroplasty, but it is based on observational, not experimental, data that suffer from the above-noted risk of confounding variables. Antibiotic-containing cement has not been approved by the U.S. Food and Drug Administration (FDA) for primary knee arthroplasty—such use is off-label. There is a theoretical concern that antibiotic-containing cement may lead to infection with resistant organisms. And then there is the issue of cost.
The authors of a previous study questioned the cost-effectiveness of antibiotic-containing bone cement in primary joint arthroplasty2. In our institution, the difference between the costs of regular bone cement and tobramycin cement would pay the wages of the nursing staff caring for that patient throughout their stay in the operating room and recovery room.
Thus, we have two studies that question the value of antibiotic-containing bone cement in primary total knee arthroplasty. The routine use of antibiotic-containing cement in primary total knee arthroplasty has weak scientific support. There may be a more compelling, but yet unsubstantiated, argument for its use in selected high-risk patients. Much of the hospital cost of joint arthroplasty is driven by surgeons’ choices of implants and supplies. We need to be active partners in the discussion of cost-effective care for our patients.
Jämsen  E;  Huhtala  H;  Puolakka  T;  Moilanen  T. Risk factors for infection after knee arthroplasty. A register-based analysis of 43,149 cases. J Bone Joint Surg Am.  2009 Jan;91(  1):38-47.[CrossRef]
 
Cummins  JS;  Tomek  IM;  Kantor  SR;  Furnes  O;  Engesaeter  LB;  Finlayson  SR. Cost-effectiveness of antibiotic-impregnated bone cement used in primary total hip arthroplasty. J Bone Joint Surg Am.  2009 Mar 1;91(  3):634-41.[CrossRef]
 

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References

Jämsen  E;  Huhtala  H;  Puolakka  T;  Moilanen  T. Risk factors for infection after knee arthroplasty. A register-based analysis of 43,149 cases. J Bone Joint Surg Am.  2009 Jan;91(  1):38-47.[CrossRef]
 
Cummins  JS;  Tomek  IM;  Kantor  SR;  Furnes  O;  Engesaeter  LB;  Finlayson  SR. Cost-effectiveness of antibiotic-impregnated bone cement used in primary total hip arthroplasty. J Bone Joint Surg Am.  2009 Mar 1;91(  3):634-41.[CrossRef]
 
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