Orthopedics

Antibiotic Bone Cements: Their Use in Routine Primary Total Joint Arthroplasty is Justified

Michael J. Dunbar, MD, FRCSC, PhD

Abstract

The use of antibiotic bone cement in total hip arthroplasty (THA) is the standard of care in countries with long-standing national registries, as data from the registries demonstrates an improvement in survivorship by reducing the incidence of both septic and aseptic failures. There is reluctance in North America to embrace antibiotic bone cement, although the percentage of use is increasing. Reasons cited for not using antibiotic cement include lack of efficacy, adverse effects on mechanical properties, increased costs, bacterial resistance, and systemic toxicity. Little to no compelling data in the literature support these claims, and significant evidence refutes them, specifically: registry data and randomized controlled trials demonstrate a clear reduction in deep joint infections with the use of antibiotic bone cement; antibiotic bone cement has lower incidence of both septic and aseptic loosening, indicating no negative effect on mechanical properties; antibiotic bone cement is cost-effective, given its proven ability to reduce revision rates and prevent poor patient outcomes; there is no evidence to support bacterial resistance, and antibiotic bone cement may reduce the incidence of resistance; and there are no reported cases of systemic toxicity from manufacturer-prepared antibiotic cement in primary THA or total knee arthroplasty.

Based on the strong evidence supporting the benefits of antibiotic bone cement and the lack of evidence against its use, it is difficult to justify why antibiotic cement is not the standard of care for primary cemented THA in North America.

Antibiotic bone cement has been used with total hip arthroplasty (THA) in the Scandinavian countries for decades with documented success.1-3 Despite this, there is considerable resistance against the use of antibiotic bone cement in the United States.4 The primary arguments proffered against the routine use of antibiotic bone cement are lack of efficacy, adverse effects on mechanical properties, increased costs, bacterial resistance, and systemic toxicity. However, significant evidence exists to refute these arguments.

Antibiotic bone cement has clear efficacy in reducing infection rates in THA. The best evidence for this comes from the Norwegian Hip Registry in a 2006 paper that reported on 56,000 cases followed over a 16-year period.1 Over this period, antibiotic bone cement clearly and significantly reduced the revision risk for both septic and aseptic loosening (Figure 1). Also, >95% of all cemented hips in Sweden are implanted with antibiotic bone cement, speaking to the weight of the Norwegian and Swedish Hip Registry data.2,3

Figure 1: Cox-adjusted survival curves with infection as endpoint for uncemented THAs, cemented THAs with antibiotic-loaded cement, and cemented THAs without antibiotic cement. (Reprinted with permission from Engesaeter LB, Espehaug B, Lie SA, Furnes O, Havelin LI. Does cement increase the risk of infection in primary total hip arthroplasty? Revision rates in 56,275 cemented and uncemented primary THAs followed for 0-16 years in the Norwegian Arthroplasty Register. Acta Orthop. 2006; 77[3]:351-358. Copyright © 2006, Nordic Orthopaedic Federation.)

In a trial by Chiu et al5 in 2002, 340 patients were randomized to undergo total knee arthroplasty (TKA) with or without antibiotic bone cement. There were no infections in the antibiotic bone cement group (0/178) and 5 in the control group (5/162). Antibiotic bone cement resulted in a significant reduction in infections (P=.24).

In a 2008 meta-analysis on antibiotic bone cement and its effect on deep-wound infection in THA, Parvizi et al6 identified 19 relevant papers and reported on 36,033 THAs. The rate of deep infection following primary THA was significantly lower when antibiotic bone cement was used (1.2% vs 2.3%). The authors concluded that the use of antibiotic bone cement lowered the infection rate by approximately 50% in primary THA.

If done by the manufacturer, the addition…

Abstract

The use of antibiotic bone cement in total hip arthroplasty (THA) is the standard of care in countries with long-standing national registries, as data from the registries demonstrates an improvement in survivorship by reducing the incidence of both septic and aseptic failures. There is reluctance in North America to embrace antibiotic bone cement, although the percentage of use is increasing. Reasons cited for not using antibiotic cement include lack of efficacy, adverse effects on mechanical properties, increased costs, bacterial resistance, and systemic toxicity. Little to no compelling data in the literature support these claims, and significant evidence refutes them, specifically: registry data and randomized controlled trials demonstrate a clear reduction in deep joint infections with the use of antibiotic bone cement; antibiotic bone cement has lower incidence of both septic and aseptic loosening, indicating no negative effect on mechanical properties; antibiotic bone cement is cost-effective, given its proven ability to reduce revision rates and prevent poor patient outcomes; there is no evidence to support bacterial resistance, and antibiotic bone cement may reduce the incidence of resistance; and there are no reported cases of systemic toxicity from manufacturer-prepared antibiotic cement in primary THA or total knee arthroplasty.

Based on the strong evidence supporting the benefits of antibiotic bone cement and the lack of evidence against its use, it is difficult to justify why antibiotic cement is not the standard of care for primary cemented THA in North America.

Antibiotic bone cement has been used with total hip arthroplasty (THA) in the Scandinavian countries for decades with documented success.1-3 Despite this, there is considerable resistance against the use of antibiotic bone cement in the United States.4 The primary arguments proffered against the routine use of antibiotic bone cement are lack of efficacy, adverse effects on mechanical properties, increased costs, bacterial resistance, and systemic toxicity. However, significant evidence exists to refute these arguments.

Lack of Efficacy

Antibiotic bone cement has clear efficacy in reducing infection rates in THA. The best evidence for this comes from the Norwegian Hip Registry in a 2006 paper that reported on 56,000 cases followed over a 16-year period.1 Over this period, antibiotic bone cement clearly and significantly reduced the revision risk for both septic and aseptic loosening (Figure 1). Also, >95% of all cemented hips in Sweden are implanted with antibiotic bone cement, speaking to the weight of the Norwegian and Swedish Hip Registry data.2,3

Figure 1: Cox-adjusted survival curves with infection as endpoint for uncemented THAs

Figure 1: Cox-adjusted survival curves with infection as endpoint for uncemented THAs, cemented THAs with antibiotic-loaded cement, and cemented THAs without antibiotic cement. (Reprinted with permission from Engesaeter LB, Espehaug B, Lie SA, Furnes O, Havelin LI. Does cement increase the risk of infection in primary total hip arthroplasty? Revision rates in 56,275 cemented and uncemented primary THAs followed for 0-16 years in the Norwegian Arthroplasty Register. Acta Orthop. 2006; 77[3]:351-358. Copyright © 2006, Nordic Orthopaedic Federation.)

In a trial by Chiu et al5 in 2002, 340 patients were randomized to undergo total knee arthroplasty (TKA) with or without antibiotic bone cement. There were no infections in the antibiotic bone cement group (0/178) and 5 in the control group (5/162). Antibiotic bone cement resulted in a significant reduction in infections (P=.24).

In a 2008 meta-analysis on antibiotic bone cement and its effect on deep-wound infection in THA, Parvizi et al6 identified 19 relevant papers and reported on 36,033 THAs. The rate of deep infection following primary THA was significantly lower when antibiotic bone cement was used (1.2% vs 2.3%). The authors concluded that the use of antibiotic bone cement lowered the infection rate by approximately 50% in primary THA.

Adverse Effects on Mechanical Properties

If done by the manufacturer, the addition of biologically active amounts of antibiotics such as gentamycin to bone cement has no effect on the mechanical properties of commonly used bone cements.7 Additionally, given that the risk of aseptic revision is also reduced with antibiotic bone cement in the Norwegian data (Figure 1), there are no adverse effects on the mechanical properties in a wide clinical setting.1

Increased Costs

It has been argued that infection rates in high-volume orthopedic centers are <1%. However, this has not been the national experience in the United States and Canada. The National Nosocomial Infection Surveillance System of the United States was used to investigate surgical site infection rates in joint replacement surgery in the United States from 1999 to 2004.8 Infection rates in hip THA were 1.7% and 2.2% in TKA. In their 2008 annual report, the Canadian Joint Replacement Registry also reports a 2.2% infection rate for THA and TKA combined.9 The incidence of infection after joint replacement is not insignificant.

An increased initial cost is associated with the use of antibiotic bone cement. However, given that the cost to treat an infected joint replacement is many times higher than the cost of the initial procedure, and given that antibiotic bone cement reduces infections, a fair argument for an overall cost savings can be made. Consider, for example, that infection accounts for approximately 20% of all revision TKAs in Sweden.10

An additional cost associated with infected joint replacement surgery is patient dissatisfaction. In a comprehensive survey of all TKA patients in Sweden, it was determined that >50% of patients were dissatisfied with the outcome of their TKA if they were revised for infection (Figure 2).11 This high rate of patient dissatisfaction underscores the clinical significance of infection and the subsequent need to continue efforts to reduce infection rates.

Figure 2:

Figure 2: Proportional distribution of patient satisfaction after infected and uninfected revision TKA in Sweden. The green bar represents “very satisfied,” the blue bar “satisfied,” the pink bar “unsure,” and the red bar “unsatisfied.” Less than 50% of patients are satisfied with the outcome of their TKA once revised for infection. (Reprinted with permission from Robertsson O, Dunbar MJ. Patient satisfaction compared with general health and disease-specific questionnaires in knee arthroplasty patients. J Arthroplasty. 2001; 16[4]:476-482. Copyright © 2001 Elsevier.)

Bacterial Resistance

No direct evidence links the development of bacterial resistance to the routine use of antibiotic bone cement for the prophylaxis of primary joint TKA or THA. However, indirect evidence suggests that antibiotic bone cement does not lead to resistance. In 2007, the SENTRY Antimicrobial Surveillance Program reported on 22,000 blood samples from patients with infection from 44 medical centers in 16 European Union countries.12 Rates of methicillin-resistant Staphylococcus aureus (MRSA) infections and development of resistance to imipenem were compared between countries. Sweden, which has used antibiotic bone cement in THA and TKA for decades, had the lowest rates of MRSA and the lowest incidence of resistance to imipenem of any country in the European Union. Prophylaxis with antibiotic bone cement that eludes antibiotics over a short period into a healthy host with low virulence loads may be less likely to promote resistance compared to treating an established infection with a high dose of antibiotics in a compromised host with a high virulence load.

Systemic Toxicity

No reports exist in the literature of systemic toxicity associated with the routine use of manufacturer-prepared antibiotic bone cement in primary THA and TKA. A study by Forsythe et al13 investigated the effect of antibiotic bone cement with tobramycin on the renal function of a group of THA patients with preexisting renal impairment. No systemic toxicity was reported, and renal function was not affected, even in a compromised group.

Conclusion

Infection in THA and TKA is a clinically relevant problem with poor outcomes. Antibiotic bone cement has been shown in registry data as well as randomized controlled trials to significantly reduce the incidence of deep infection, with no evidence to suggest adverse effects on mechanical properties, development of resistance, or toxicity. Given the costs associated with the treatment of infected arthroplasties and financial and patient centric metrics such as satisfaction, antibiotic bone cement is cost effective. Antibiotic bone cement should be used routinely in all primary THAs and TKAs.

References

  1. Engesaeter LB, Espehaug B, Lie SA, Furnes O, Havelin LI. Does cement increase the risk of infection in primary total hip arthroplasty? Revision rates in 56,275 cemented and uncemented primary THAs followed for 0-16 years in the Norwegian Arthroplasty Register. Acta Orthop. 2006; 77(3): 351-358.
  2. Herberts P, Malchau H. Long-term registration has improved the quality of hip replacement: a review of the Swedish THR Register comparing 160,000 cases. Acta Orthop Scand. 2000; 71(2):111-121.
  3. Malchau H, Herberts P, Eisler T, Garellick G, Söderman P. The Swedish Total Hip Replacement Register. J Bone Joint Surg Am. 2002; 84(Suppl 2):2-20.
  4. Jiranek WA, Hanssen AD, Greenwald AS. Antibiotic-loaded bone cement for infection prophylaxis in total joint replacement. J Bone Joint Surg Am. 2006; 88(11):2487-2500.
  5. Chiu FY, Chen CM, Lin CF, Lo WH. Cefuroxime-impregnated cement in primary total knee arthroplasty: a prospective, randomized study of three hundred and forty knees. J Bone Joint Surg Am. 2002; 84(5):759-762.
  6. Parvizi J, Saleh KJ, Ragland PS, Pour AE, Mont MA. Efficacy of antibiotic-impregnated cement in total hip replacement. Acta Orthop. 2008; 79(3): 335-341.
  7. Davies JP, O’Connor DO, Burke DW, Harris WH. 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. 1989; 23(4):379-397.
  8. Barnes S, Salemi C, Fithian D, et al. An enhanced benchmark for prosthetic joint replacement infection rates. Am J Infect Control. 2006; 34(10):669-672.
  9. Canadian Institute for Health Information. Canadian Joint Replacement Registry (CJRR) 2007 Annual Report—Hip and Knee Replacements in Canada. Ottawa, Canada: Canadian Institute for Health Information; 2008.
  10. Department of Orthopedics, Lund University Hospital. The Swedish Knee Arthroplasty Annual Report 2008. Lund, Sweden: University of Lund; 2008.
  11. Robertsson O, Dunbar MJ. Patient satisfaction compared with general health and disease-specific questionnaires in knee arthroplasty patients. J Arthroplasty. 2001; 16(4):476-482.
  12. Sader H, Fritsche T, Stillwell M, Jones R. 10 years of surveillance of bloodstream infections in European medical centres by the SENTRY Antimicrobial Surveillance Program (1997–2006). Paper presented at: 17th European Congress of Clinical Microbiology and Infectious Diseases; March 31-April 3, 2007; Munich, Germany.
  13. Forsythe ME, Crawford S, Sterling GJ, Whitehouse SL, Crawford R. Safeness of Simplex-tobramycin bone cement in patients with renal dysfunction undergoing total hip replacement. J Orthop Surg (Hong Kong). 2006; 14(1):38-42.

Author

Dr Dunbar is from Dalhousie University, Halifax, Nova Scotia, Canada.

Dr Dunbar is a consultant for Stryker Orthopaedics and has received institution research support from DePuy, Wright Medical Technology, Smith & Nephew, and Zimmer.

Presented at Current Concepts in Joint Replacement 2008 Winter Meeting; December 10-13, 2008; Orlando, Florida.

Correspondence should be addressed to: Michael J. Dunbar MD, FRCSC, PhD, Dalhousie University, 1796 Summer St, Ste 4822, Halifax, Nova Scotia, B3H 3A7 Canada.

DOI: 10.3928/01477447-20090728-20

10.3928/01477447-20090728-20

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