Chapter 82 What Is the Role of Antibiotic Cement in Total Joint Replacement?
Deep wound infection after total joint arthroplasty can be a devastating complication for the patient. Data from the Swedish Knee Registry demonstrates a deep infection rate after total knee arthroplasty (TKA) of 1.7% in patients with osteoarthrosis and 4.4% in patients with rheumatoid arthritis.1 Data from other large series of patients have shown infection rates to be between 0.2% to 1%.2–4 Antibiotic-loaded bone cement (ALBC) is a well-accepted adjunct in the treatment of an established infection. However, its role in the prevention of infection remains controversial because of issues regarding drug resistance, sensitivity, efficacy, and cost.
BACKGROUND
The course and amount of antibiotic that is released from the cement depends on the porosity and the overall surface area of the bone cement exposed. Antibiotic is released from the surface of the cement, and also from cracks and voids in the cement.5,6
Palacos (Zimmer, Warsaw, IN, USA) bone cement has been shown to have greater elution levels than other types of bone cement.7,8 This difference is attributed to the increased porosity of Palacos cement. Although the majority of the antibiotic release occurs in the first 9 weeks, late fracture of the cement mantle can liberate substantial levels of antibiotic many years after implantation.9,10
Commercially prepared antibiotic cement may be superior to cement in which antibiotics are mixed intraoperatively. Elution of gentamicin and tobramycin from surgeon-mixed Simplex (Stryker, Mahwah, NJ, USA) or Palacos beads compared with elution from commercially prepared gentamicin-PMMA (Septopal, Biomet, Warsaw, IN, USA) beads showed that more total antibiotic was released from the latter and was maintained at greater concentrations than it was in the cement to which antibiotics were mixed by hand.11
Some antibiotics elute better from bone cement than others.12 A study of antibiotic elution from Simplex bone cement examined cefazolin (4.5 g per 40 g cement powder), ciprofloxacin (6 g per 40 g powder), clindamycin (6 g per 40 g powder), ticarcillin (12 g per 40 g powder), tobramycin (9.8 g per 40 g powder), and vancomycin (4 g per 40 g powder). The authors conclude that clindamycin, vancomycin, and tobramycin displayed the best elution characteristics into bone and granulation tissue.13
The use of local antibiotic delivery from ALBC in the treatment of musculoskeletal infection is well established.14–17 It has been shown that at least 3.6 g antibiotic per 40 g cement is optimal for the best elution kinetics and sustained therapeutic levels.18 Doses as high as 6 to 8 g antibiotic per 40 g bone cement have been shown to be safe clinically.17 The use of these high doses is important for the sustained release of antibiotics at levels that are bacteriocidal for the organisms being treated.
PROPHYLAXIS
Total Knee Arthroplasty
The use of ALBC for treating active infections in joint arthroplasty has been well established. The basis for the use of ALBC as a prophylactic measure is to reduce the prevalence of deep joint infection. Gentamicin, cefuroxime, and tobramycin are the antibiotics most commonly used in bone cement in clinical studies worldwide.19–22 Of the three antibiotics, gentamicin has been used most frequently and studied most extensively.23 We are not aware of any clinical studies comparing the efficacy of one antibiotic over another as a prophylaxis in cement.
In a randomized clinical trial of 340 primary TKAs, Chiu and colleagues19 evaluated the deep infection rates for patients with cefuroxime bone cement as compared with standard bone cement. No deep infections occurred in the study group, whereas a deep infection developed in 5 of the 162 knees (3.1%) in the control group (P = 0.02). Even with the small sample size, a significant reduction in deep infections was noted with the use of antibiotic bone cement.
The same authors then performed a second prospective randomized trial on just 78 patients with diabetes undergoing primary TKA.20 Once again, cefuroxime bone cement was used in one group and standard bone cement in the other. The authors note a significant reduction in deep infection rate in this high-risk patient population with the use of antibiotic bone cement (P < 0.02). The reported a deep infection rate of 13.5% (5/37) in the control group and no infections in the ALBC group. This overall infection rate for patients with diabetes is greater than that reported in the literature of 3.1% to 7%.24–26
In another randomized trial, McQueen and coworkers27 found that, in 295 patients undergoing primary hip or knee replacement, there was no difference in infection rates between the use of cefuroximeimpregnated bone cement or administration of the cefuroxime intravenously. They report an overall infection rate of 6.8%.
Prophylaxis: Total Hip Arthroplasty
Josefsson and Kolmert28 performed a large randomized trial of 1688 patients undergoing hip replacement and found that at 2 years, the group treated with intravenous antibiotics had a deep infection rate of 1.6% (13/835) versus 0.4% (3/853) in the group treated with gentamycin-impregnated bone cement (P < 0.05).
Espehaug and coauthors21 report on 10,905 primary cemented total hip replacements from the Norwegian Arthroplasty Registry. There were four treatment groups: (1) systemic antibiotics and antibiotic-impregnated bone cement, (2) systemic antibiotics only, (3) antibiotic-impregnated bone cement only, and (4) no antibiotic prophylaxis. The overall infection rate was 0.4%. The use of antibiotic bone cement and systemic antibiotics was found to be significantly more effective in preventing deep infection than using either systemic antibiotics or antibiotic bone cement alone (P < 0.001). The adjusted failure rate ratios in the remaining groups were 4.3 (systemic antibiotics only), 6.3 (antibiotic-impregnated cement only), and 11.5 (no antibiotic prophylaxis). The authors conclude that the best prophylaxis against infection was a combination of systemic antibiotics and antibiotic-impregnated cement.
The Swedish Hip Registry data consisted of 92,675 primary and revision total hip replacements performed between 1978 and 1990. Malchau and researchers22 found that the quality of the operating room ventilation and the use of gentamycin-impregnated antibiotic bone cement were the only significant factors in reducing deep infection (P < 0.001). Also, the benefit was greater for revision surgery than for primary hip replacements. Interestingly, the data showed a decrease in deep infection rates from 1979 to 1991 in all patients, regardless of the use of ALBC, because of other measures of infection control introduced over this period.
A large retrospective study of 22,170 primary total hip replacements from the Norwegian Arthroplasty Register during the period of 1987 to 2001 was reported by Engesaeter and investigators.29 Patients who received only systemic antibiotic prophylaxis (5960 patients) had a 1.8 times greater rate of infection than patients who received systemic antibiotic prophylaxis combined with gentamicin-loaded bone cement (15,676 patients) (P = 0.01).
In another retrospective review of 1542 total hip replacements, no difference was found in infection rate between primary total hip replacements performed with (1.65%) compared with those performed without gentamicin-loaded bone cement (1.72%).30
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