- Email: [email protected]
Prophylactic use of antibiotic bone cement
The Journal of Arthroplasty Vol. 19 No. 4 Suppl. 1 2004
Prophylactic Use of Antibiotic Bone Cement An Emerging Standard—In the Affirmative Robert B. Bourne, MD, FRCSC
Abstract: Deep infection is a devastating complication following total joint arthroplasty. Preclinical testing; randomized; clinical trials; national joint replacement data; and our experience indicate that the use of antibiotic-impregnated bone cement is a potentially effective strategy in reducing the risk of deep infection following both primary and revision total joint arthroplasty. Allergic reactions, bacterial resistance, and cost represent barriers to the widespread use of antibiotic bone cement. Key words: prophylactic, antibiotic, bone cement. © 2004 Elsevier Inc. All rights reserved.
(FDA) in the United States, at least for use in infected total joint arthroplasties. In this article, I provide evidence that antibiotic bone cements have been studied more than we appreciate in North America and that we should be considering the use of such antibiotic-impregnated bone cements during primary joint arthroplasties. I approach this topic by using the criteria proposed by Dr. Henrik Malchau in his PhD thesis on how to introduce new technology to orthopedic surgery, namely through preclinical testing; randomized, clinical trials; multicenter studies; and postmarket surveillance [13].
Deep infection following total knee arthroplasty (TKA) is a devastating complication [1,2]. The risk of deep infection is greater following TKA than total hip arthroplasty (THA) [3,4]. According to the Swedish Knee Registry, deep infection following TKA occurs in 1.7% of osteoarthritic and 4.4% of rheumatoid arthritis patients [5]. An infected TKA leads to an unhappy patient, a surgeon with a tarnished reputation, and an event that is extremely costly to treat. Most surgeons would agree that prevention is important. Increasingly, use of antibiotic-impregnated bone cement is becoming the standard of practice in Europe and Scandinavia, both for primary and revision knee and hip arthroplasties [6 –12]. The quality of air ventilation and the use of antibioticimpregnated bone cement has led to a stepwise reduction in deep infections (Fig. 1) [6]. During the past few months, antibiotic bone cement has been approved by the Food and Drug Administration
Preclinical Testing Antibiotic-impregnated bone cement demonstrates highly effective bactericidal activity for at least 7 to 10 days, and in some studies, for up to 10 years [4,8 –10,14]. This testing also has revealed that many antibiotics are heat-stable (Table 1). Biomechanical testing has revealed that whereas the addition of high-dose antibiotics may weaken bone cement, the low-dose, antibiotic-impregnated bone cements that are used in clinical practice have negligible reductions in static and fatigue strengths, and that fixation is not compromised [3,4,15–19]. Laboratory studies also have revealed that some bone
From the London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada. No benefits or funds were received in support of this study. Reprint requests: Dr. R. B. Bourne, London Health Sciences Centre, 339 Windermere Road, London, Ontario, N6A 5A5, Canada. © 2004 Elsevier Inc. All rights reserved. 0883-5403/04/1904-1015$30.00/0 doi:10.1016/j.arth.2004.03.005
69
70 The Journal of Arthroplasty Vol. 19 No. 4 Suppl. 1 June 2004
National Joint Replacement Registry Studies
Fig. 1. Stepwise reduction in deep infection following THA in Sweden (from Malchau et al: Acta Orthop Scand 64:497, 1993).
cements are better than others in terms of the amount of antibiotic elution [8,9,19 –21]. In addition, radiostereometric analysis (RSA) studies have revealed comparable fixation of cemented implants with and without antibiotic-impregnated bone cement [15].
Randomized, Clinical Trials In a randomized clinical trial of 340 primary TKAs, Chiu et al. compared the infection rates for patients who used Cefuroxime bone cement as with standard bone cement [16]. Even with this small patient population, a significant reduction in deep infections was noted with the use of antibiotic bone cement (P⬍0.02). The same authors then performed a second clinical trial on 78 diabetic patients undergoing TKA for osteoarthritis of the knee [17]. Once again, Cefuroxime bone cement was used in one group and standard bone cement in the other. The authors noted a significant reduction in deep infections in this high-risk patient population with the use of antibiotic bone cement (P⬎0.02).
Espehaug et al. reported on the Norwegian Arthroplasty Register results in 10,905 primary cemented THAs [11]. High-viscosity bone cement was used in all patients. There were 4 groups in terms of deep infection prophylaxis, namely patients treated with antibiotic bone cement and systemic antibiotics (N ⫽ 5,804), patients who had systemic antibiotics alone (N ⫽ 4,586), patients in whom antibiotic bone cement was used alone (N ⫽ 239), and patients who received no deep infection prophylaxis (N ⫽ 276). The use of antibiotic bone cement and systemic antibiotics was found to be significantly more effective in preventing deep infection than using systemic antibiotics alone or antibiotic bone cement (P⬍0.001) (Fig. 2). As a consequence, in Norway, the use of antibiotic-containing bone cement has increased from approximately 40% to over 90% of THAs from 1987 to 1998 (Fig. 3). The Swedish Hip Registry also examined this issue. In an analysis of 92,675 primary THAs performed between 1978 and 1990, Malchau et al. found that the quality of operating room ventilation and the use of antibiotic-containing bone cement (Gentamicin) were the only significant factors in reducing deep infection (P⬍0.001) [6 –13]. The Swedish Hip Registry also demonstrated a step-wise reduction in deep infection from 1979 to 1991 with the use of better operating room ventilation and antibiotic-impregnated bone cement (Fig. 1). Using Poisson modeling, the Swedish Joint Replacement Registry demonstrated that Palacos Gentamicin bone cement was associated with the lowest revision rates following THA. Finally, investigators in Sweden have found that the use of antibiotic bone cement was cost-effective in eliminating infection and reducing the costs of difficult revisions.
Table 1. A List of Heat-Stable Antibiotics That Have Been Used in Antibiotic-Impregnated Polymethylmethacrylate Bone Cements Gentamicin Clindamycin Cephalothin Tobramycin Erythromycin Oxacillin Cefuroxime
Colistin Methacillin Tetracycline Lincomycin Dicloxacillin Bactrim
Prophylactic Use of Antibiotic Bone Cement • Robert B. Bourne
71
Our Hospital Results For a short time, our hospital was left in a position in which one operating room had vertical laminar airflow and the second operating room had only standard ventilation. We were concerned with the increase risk for deep infection in the standard operating room. We therefore adopted a strategy to use antibiotic-impregnated Simplex bone cement to which the manufacturer had added Erythromycin and Colistin. We were able to review our deep infections following cemented TKA in 1,161 patients; 493 of whom had their surgery performed in the conventional operating room, and 668 had their surgery under laminar airflow. For both groups, the deep infection rate was 0.6%, suggesting that the use of antibiotic bone cement is at least as effective as vertical laminar airflow in preventing infection.
Discussion Considerable evidence has been published on the effectiveness of the antibiotic bone cement in preventing deep infection following total joint arthroplasty [6,9 –12]. One might ask why the regulatory bodies in North America have been so slow to approve and allow the sale of antibiotic-impregnated bone cement. One concern has been the fear
Fig. 2. Effectiveness of antibiotic bone cement and systemic antibiotics, systemic antibiotics alone, antibiotic cement alone, and no prophylaxis on preventing deep infection following THA (from Espehaug et al: J Bone Joint Surg 79B:590, 1997).
Fig. 3. Increasing use of antibiotic bone cement during THA in Norway (from Espehaug et al: J Bone Joint Surg 79B:590, 1997).
of allergic reactions. Despite the use of antibiotic bone cement in more than 100,000 patients, no reports of an allergic reaction have been noted. Most studies have been done using Gentamicin bone cement, an antibiotic not noted to produce allergic reactions. The use of other antibiotics in bone cement require further study and postmarket surveillance. Similarly, there has been no evidence of toxic effects locally or systemically. Another potential concern with the use of antibiotic-impregnated bone cement is the development of drugresistant organisms in the hospital setting. This has been assessed in Sweden, and the changes have been minor, namely a slight increase in coagulasenegative Staphylococcus and a small drop in Gramnegative organisms. Continued postmarket surveillance is warranted to assure the safety of antibiotic bone cements with regard to allergic reactions, toxic effects, or the emergence of antibiotic-resistant organisms. A national joint arthroplasty registry such as those found in Sweden, Norway, Australia, New Zealand, or Canada would be helpful in this regard. The final issue is increased cost of antibiotic bone cements. Future economic assessments of the costto-benefit of these cements is warranted. In conclusion, preclinical testing; randomized, clinical trials; and postmarket surveillance as provided by national joint arthroplasty registries have confirmed the effectiveness of antibiotic-impregnated bone cement in reducing deep infection following total joint arthroplasty. Potential risks do not appear to have materialized. Postmarket surveillance of these antibiotic bone cements is warranted. Cost remains an issue and needs further study. Antibiotics in bone cement have a more definitive role in high-risk patients such as those with compromised immune systems (ie, rheumatoid arthritis, lupus, immunosuppression, diabetes mellitus, age older than 75, and in patients requiring revision surgery).
72 The Journal of Arthroplasty Vol. 19 No. 4 Suppl. 1 June 2004
References 1. Garvin KL, Hanssen AD: Infection after total hip arthroplasty: Past, present and future. J Bone Joint Surg Am 77:1576, 1995 2. Joseph TN, Chen AL, DiCesare PE: Use of antibioticimpregnated cement in total joint arthroplasty. J Am Acad Orthop Surg 11:38, 2003 3. Davies JP, Harris WH: Effect of hand mixing tobramycin on the fatigue strength of Simplex P. J Biomed Mater Res 25:1409, 1991 4. Masari BA, Duncan CP, Beauchamp CP: Long-term elution of antibiotics from bone cement: an in vivo study using the prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) system. J Arthroplasty 13: 331, 1998 5. Robertsson O, Knutson K, Lewold S, et al: The Swedish knee arthroplasty register 1975–1997: an update with special emphasis of 41,223 knees operated on in 1988 –1997. Acta Orthop Scand 72:603, 2001 6. Malchau H, Herberts P, Ahnfelt L: Prognosis of total hip replacement in Sweden. Follow-up of 92,675 operations performed 1978 –1990. Acta Orthop Scand 64:497, 1993 7. Aebi B, Gerber C, Ganz R: Prevention of infection in elective orthopaedic interventions with special reference to alloplastic joint replacement. Hebv Chin Acta 56:387, 1989 8. Buchholz HW, Elson RA, Engelbrecht E, et al: Management of deep infection of total hip replacement. J Bone Joint Surg Br 63:342, 1981 9. Carlsson AS, Josefsson G, Lindberg L: Revision with gentamicin-impregnated cement for deep infections in total hip arthroplasties. J Bone Joint Surg Am 60:1059, 1978 10. Davies JP, O’Connor DO, Burke DW, et al: Influence of antibiotic impregnation on the fatigue life of Simplex P and Palacos R acrylic bone cements with and without centrifugation. J Biomed Mater Res 23:379, 1989 11. Espehaug B, Engesaeter LB, Vollset SE, et al: Antibiotic prophylaxis in total hip arthroplasty: Review of 10,905 primary cemented total hip replacements re-
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
ported to the Norwegian arthroplasty register, 1987 to 1995. J Bone Joint Surg Br 79:590, 1997 Wilson NI: A survey in Scotland of measures to prevent infection following orthopaedic surgery. J Hosp Infect 9:235, 1987 Malchau H: On the importance of stepwise introduction of new hip implant technology. Assessment of total hip replacement using clinical evaluation, radiostereometry, digitized radiography and a national hip registry. PhD thesis. Institute of Surgical Sciences, Go¨ etborg University, Go¨ teborg, Sweden; 1995 Trippel SB: Antibiotic-impregnated cement in total joint arthroplasty. J Bone Joint Surg Am 68:1297, 1986 Adelberth G, Nilsson KG, Karrholm J, et al: Fixation of the tibial component using CMW-1 or Palacos bone cement with gentamicin: similar outcome in a randomized radiostereometric study of 51 total knee arthroplasties. Acta Orthop Scand 73:531, 2002 Chiu FY, Chen CM, Lin CFJ, et al: Cefuroximeimpregnated cement in primary total knee arthroplasty. J Bone Joint Surg Am 84:759, 2002 Chiu FY, Lin CF, Chen CM, et al: Cefuroxime-impregnated cement at primary total knee arthroplasty in diabetes mellitus. A prospective, randomized study. J Bone Joint Surg Br 83:691, 2001 Josefsson G, Gudmundsson G, Kolmert L, et al: Prophylaxis with systemic antibiotics versus gentamicin bone cement in total hip arthroplasty: A five-year survey of 1688 hips. Clin Orthop 253:173, 1990 Klekamp J, Dawson JM, Haas DW, et al: The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint arthroplasty. J Arthroplasty 14:339, 1999 Powles JW, Spencer RF, Lovering AM: Gentamicin release from old cement during revision hip arthroplasty. J Bone Joint Surg Br 80:607, 1998 Younger AS, Duncan CP, Masri BA: Treatment of infection associated with segmental bone loss in the proximal part of the femur in two stages with use of an antibiotic-loaded interval prosthesis. J Bone Joint Surg Am 80:60, 1998
Prophylactic Use of Antibiotic Bone Cement An Emerging Standard—In the Affirmative Robert B. Bourne, MD, FRCSC
Abstract: Deep infection is a devastating complication following total joint arthroplasty. Preclinical testing; randomized; clinical trials; national joint replacement data; and our experience indicate that the use of antibiotic-impregnated bone cement is a potentially effective strategy in reducing the risk of deep infection following both primary and revision total joint arthroplasty. Allergic reactions, bacterial resistance, and cost represent barriers to the widespread use of antibiotic bone cement. Key words: prophylactic, antibiotic, bone cement. © 2004 Elsevier Inc. All rights reserved.
(FDA) in the United States, at least for use in infected total joint arthroplasties. In this article, I provide evidence that antibiotic bone cements have been studied more than we appreciate in North America and that we should be considering the use of such antibiotic-impregnated bone cements during primary joint arthroplasties. I approach this topic by using the criteria proposed by Dr. Henrik Malchau in his PhD thesis on how to introduce new technology to orthopedic surgery, namely through preclinical testing; randomized, clinical trials; multicenter studies; and postmarket surveillance [13].
Deep infection following total knee arthroplasty (TKA) is a devastating complication [1,2]. The risk of deep infection is greater following TKA than total hip arthroplasty (THA) [3,4]. According to the Swedish Knee Registry, deep infection following TKA occurs in 1.7% of osteoarthritic and 4.4% of rheumatoid arthritis patients [5]. An infected TKA leads to an unhappy patient, a surgeon with a tarnished reputation, and an event that is extremely costly to treat. Most surgeons would agree that prevention is important. Increasingly, use of antibiotic-impregnated bone cement is becoming the standard of practice in Europe and Scandinavia, both for primary and revision knee and hip arthroplasties [6 –12]. The quality of air ventilation and the use of antibioticimpregnated bone cement has led to a stepwise reduction in deep infections (Fig. 1) [6]. During the past few months, antibiotic bone cement has been approved by the Food and Drug Administration
Preclinical Testing Antibiotic-impregnated bone cement demonstrates highly effective bactericidal activity for at least 7 to 10 days, and in some studies, for up to 10 years [4,8 –10,14]. This testing also has revealed that many antibiotics are heat-stable (Table 1). Biomechanical testing has revealed that whereas the addition of high-dose antibiotics may weaken bone cement, the low-dose, antibiotic-impregnated bone cements that are used in clinical practice have negligible reductions in static and fatigue strengths, and that fixation is not compromised [3,4,15–19]. Laboratory studies also have revealed that some bone
From the London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada. No benefits or funds were received in support of this study. Reprint requests: Dr. R. B. Bourne, London Health Sciences Centre, 339 Windermere Road, London, Ontario, N6A 5A5, Canada. © 2004 Elsevier Inc. All rights reserved. 0883-5403/04/1904-1015$30.00/0 doi:10.1016/j.arth.2004.03.005
69
70 The Journal of Arthroplasty Vol. 19 No. 4 Suppl. 1 June 2004
National Joint Replacement Registry Studies
Fig. 1. Stepwise reduction in deep infection following THA in Sweden (from Malchau et al: Acta Orthop Scand 64:497, 1993).
cements are better than others in terms of the amount of antibiotic elution [8,9,19 –21]. In addition, radiostereometric analysis (RSA) studies have revealed comparable fixation of cemented implants with and without antibiotic-impregnated bone cement [15].
Randomized, Clinical Trials In a randomized clinical trial of 340 primary TKAs, Chiu et al. compared the infection rates for patients who used Cefuroxime bone cement as with standard bone cement [16]. Even with this small patient population, a significant reduction in deep infections was noted with the use of antibiotic bone cement (P⬍0.02). The same authors then performed a second clinical trial on 78 diabetic patients undergoing TKA for osteoarthritis of the knee [17]. Once again, Cefuroxime bone cement was used in one group and standard bone cement in the other. The authors noted a significant reduction in deep infections in this high-risk patient population with the use of antibiotic bone cement (P⬎0.02).
Espehaug et al. reported on the Norwegian Arthroplasty Register results in 10,905 primary cemented THAs [11]. High-viscosity bone cement was used in all patients. There were 4 groups in terms of deep infection prophylaxis, namely patients treated with antibiotic bone cement and systemic antibiotics (N ⫽ 5,804), patients who had systemic antibiotics alone (N ⫽ 4,586), patients in whom antibiotic bone cement was used alone (N ⫽ 239), and patients who received no deep infection prophylaxis (N ⫽ 276). The use of antibiotic bone cement and systemic antibiotics was found to be significantly more effective in preventing deep infection than using systemic antibiotics alone or antibiotic bone cement (P⬍0.001) (Fig. 2). As a consequence, in Norway, the use of antibiotic-containing bone cement has increased from approximately 40% to over 90% of THAs from 1987 to 1998 (Fig. 3). The Swedish Hip Registry also examined this issue. In an analysis of 92,675 primary THAs performed between 1978 and 1990, Malchau et al. found that the quality of operating room ventilation and the use of antibiotic-containing bone cement (Gentamicin) were the only significant factors in reducing deep infection (P⬍0.001) [6 –13]. The Swedish Hip Registry also demonstrated a step-wise reduction in deep infection from 1979 to 1991 with the use of better operating room ventilation and antibiotic-impregnated bone cement (Fig. 1). Using Poisson modeling, the Swedish Joint Replacement Registry demonstrated that Palacos Gentamicin bone cement was associated with the lowest revision rates following THA. Finally, investigators in Sweden have found that the use of antibiotic bone cement was cost-effective in eliminating infection and reducing the costs of difficult revisions.
Table 1. A List of Heat-Stable Antibiotics That Have Been Used in Antibiotic-Impregnated Polymethylmethacrylate Bone Cements Gentamicin Clindamycin Cephalothin Tobramycin Erythromycin Oxacillin Cefuroxime
Colistin Methacillin Tetracycline Lincomycin Dicloxacillin Bactrim
Prophylactic Use of Antibiotic Bone Cement • Robert B. Bourne
71
Our Hospital Results For a short time, our hospital was left in a position in which one operating room had vertical laminar airflow and the second operating room had only standard ventilation. We were concerned with the increase risk for deep infection in the standard operating room. We therefore adopted a strategy to use antibiotic-impregnated Simplex bone cement to which the manufacturer had added Erythromycin and Colistin. We were able to review our deep infections following cemented TKA in 1,161 patients; 493 of whom had their surgery performed in the conventional operating room, and 668 had their surgery under laminar airflow. For both groups, the deep infection rate was 0.6%, suggesting that the use of antibiotic bone cement is at least as effective as vertical laminar airflow in preventing infection.
Discussion Considerable evidence has been published on the effectiveness of the antibiotic bone cement in preventing deep infection following total joint arthroplasty [6,9 –12]. One might ask why the regulatory bodies in North America have been so slow to approve and allow the sale of antibiotic-impregnated bone cement. One concern has been the fear
Fig. 2. Effectiveness of antibiotic bone cement and systemic antibiotics, systemic antibiotics alone, antibiotic cement alone, and no prophylaxis on preventing deep infection following THA (from Espehaug et al: J Bone Joint Surg 79B:590, 1997).
Fig. 3. Increasing use of antibiotic bone cement during THA in Norway (from Espehaug et al: J Bone Joint Surg 79B:590, 1997).
of allergic reactions. Despite the use of antibiotic bone cement in more than 100,000 patients, no reports of an allergic reaction have been noted. Most studies have been done using Gentamicin bone cement, an antibiotic not noted to produce allergic reactions. The use of other antibiotics in bone cement require further study and postmarket surveillance. Similarly, there has been no evidence of toxic effects locally or systemically. Another potential concern with the use of antibiotic-impregnated bone cement is the development of drugresistant organisms in the hospital setting. This has been assessed in Sweden, and the changes have been minor, namely a slight increase in coagulasenegative Staphylococcus and a small drop in Gramnegative organisms. Continued postmarket surveillance is warranted to assure the safety of antibiotic bone cements with regard to allergic reactions, toxic effects, or the emergence of antibiotic-resistant organisms. A national joint arthroplasty registry such as those found in Sweden, Norway, Australia, New Zealand, or Canada would be helpful in this regard. The final issue is increased cost of antibiotic bone cements. Future economic assessments of the costto-benefit of these cements is warranted. In conclusion, preclinical testing; randomized, clinical trials; and postmarket surveillance as provided by national joint arthroplasty registries have confirmed the effectiveness of antibiotic-impregnated bone cement in reducing deep infection following total joint arthroplasty. Potential risks do not appear to have materialized. Postmarket surveillance of these antibiotic bone cements is warranted. Cost remains an issue and needs further study. Antibiotics in bone cement have a more definitive role in high-risk patients such as those with compromised immune systems (ie, rheumatoid arthritis, lupus, immunosuppression, diabetes mellitus, age older than 75, and in patients requiring revision surgery).
72 The Journal of Arthroplasty Vol. 19 No. 4 Suppl. 1 June 2004
References 1. Garvin KL, Hanssen AD: Infection after total hip arthroplasty: Past, present and future. J Bone Joint Surg Am 77:1576, 1995 2. Joseph TN, Chen AL, DiCesare PE: Use of antibioticimpregnated cement in total joint arthroplasty. J Am Acad Orthop Surg 11:38, 2003 3. Davies JP, Harris WH: Effect of hand mixing tobramycin on the fatigue strength of Simplex P. J Biomed Mater Res 25:1409, 1991 4. Masari BA, Duncan CP, Beauchamp CP: Long-term elution of antibiotics from bone cement: an in vivo study using the prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) system. J Arthroplasty 13: 331, 1998 5. Robertsson O, Knutson K, Lewold S, et al: The Swedish knee arthroplasty register 1975–1997: an update with special emphasis of 41,223 knees operated on in 1988 –1997. Acta Orthop Scand 72:603, 2001 6. Malchau H, Herberts P, Ahnfelt L: Prognosis of total hip replacement in Sweden. Follow-up of 92,675 operations performed 1978 –1990. Acta Orthop Scand 64:497, 1993 7. Aebi B, Gerber C, Ganz R: Prevention of infection in elective orthopaedic interventions with special reference to alloplastic joint replacement. Hebv Chin Acta 56:387, 1989 8. Buchholz HW, Elson RA, Engelbrecht E, et al: Management of deep infection of total hip replacement. J Bone Joint Surg Br 63:342, 1981 9. Carlsson AS, Josefsson G, Lindberg L: Revision with gentamicin-impregnated cement for deep infections in total hip arthroplasties. J Bone Joint Surg Am 60:1059, 1978 10. Davies JP, O’Connor DO, Burke DW, et al: Influence of antibiotic impregnation on the fatigue life of Simplex P and Palacos R acrylic bone cements with and without centrifugation. J Biomed Mater Res 23:379, 1989 11. Espehaug B, Engesaeter LB, Vollset SE, et al: Antibiotic prophylaxis in total hip arthroplasty: Review of 10,905 primary cemented total hip replacements re-
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
ported to the Norwegian arthroplasty register, 1987 to 1995. J Bone Joint Surg Br 79:590, 1997 Wilson NI: A survey in Scotland of measures to prevent infection following orthopaedic surgery. J Hosp Infect 9:235, 1987 Malchau H: On the importance of stepwise introduction of new hip implant technology. Assessment of total hip replacement using clinical evaluation, radiostereometry, digitized radiography and a national hip registry. PhD thesis. Institute of Surgical Sciences, Go¨ etborg University, Go¨ teborg, Sweden; 1995 Trippel SB: Antibiotic-impregnated cement in total joint arthroplasty. J Bone Joint Surg Am 68:1297, 1986 Adelberth G, Nilsson KG, Karrholm J, et al: Fixation of the tibial component using CMW-1 or Palacos bone cement with gentamicin: similar outcome in a randomized radiostereometric study of 51 total knee arthroplasties. Acta Orthop Scand 73:531, 2002 Chiu FY, Chen CM, Lin CFJ, et al: Cefuroximeimpregnated cement in primary total knee arthroplasty. J Bone Joint Surg Am 84:759, 2002 Chiu FY, Lin CF, Chen CM, et al: Cefuroxime-impregnated cement at primary total knee arthroplasty in diabetes mellitus. A prospective, randomized study. J Bone Joint Surg Br 83:691, 2001 Josefsson G, Gudmundsson G, Kolmert L, et al: Prophylaxis with systemic antibiotics versus gentamicin bone cement in total hip arthroplasty: A five-year survey of 1688 hips. Clin Orthop 253:173, 1990 Klekamp J, Dawson JM, Haas DW, et al: The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint arthroplasty. J Arthroplasty 14:339, 1999 Powles JW, Spencer RF, Lovering AM: Gentamicin release from old cement during revision hip arthroplasty. J Bone Joint Surg Br 80:607, 1998 Younger AS, Duncan CP, Masri BA: Treatment of infection associated with segmental bone loss in the proximal part of the femur in two stages with use of an antibiotic-loaded interval prosthesis. J Bone Joint Surg Am 80:60, 1998