The Journal of Arthroplasty Vol. 24 No. 7 2009

Antibiotic Bone Cement and the Incidence of DeepInfection after Total Knee Arthroplasty

Rajiv Gandhi, MD,* Fahad Razak, MD,*y Rubini Pathy, MD,* J. Roderick Davey, MD,*Khalid Syed, MD,* and Nizar N. Mahomed, MD, ScD*

Abstract: We asked if the use of antibiotic-laden bone cement (ALBC) decreased thedeep infection rate after primary total knee arthroplasty as compared to plain bonecement. We surveyed 1625 consecutive patients for relevant covariates. Joint painand function were assessed at baseline and at 1 year of follow-up with the WesternOntario McMaster University Osteoarthritis Index scores. The incidence of deepinfection at 1-year follow-up was recorded. There were no differences in baselinecovariates between groups (P N .05). We found a deep infection rate of 2.2% in theALBC group and 3.1% in the plain bone cement group (P = .27). Adjusted analysisshowed that ALBC was not predictive of a lower infection rate at 1 year (P = .84).Antibiotic-laden bone cement did not reduce the incidence of deep infectionfollowing primary total knee arthroplasty at 1-year follow-up. Keywords: kneearthroplasty, infection, antibiotic cement, prophylaxis.© 2009 Elsevier Inc. All rights reserved.

Deepknee infection can be a devastating complicationof total knee arthroplasty (TKA). Infection rates of 1%to 3% have been reported in patients undergoingknee arthroplasty for osteoarthritis [1-3] and up to8% for patients having a knee replacement forrheumatoid arthritis [4-6].Kurtz et al [7,8] have shown that the incidence of

deep infection after primary TKA is rising andprojected to reach 6.8% by 2030. The health carecosts for treating joint sepsis after arthroplasty hasbeen estimated at being 40 to 80 million annually inthe United States [9]. Sculco [10] estimates thedirect costs of revision surgery for deep infection atbeing over $55 000 per case. Thus, prevention of

From the *Division of Orthopedic Surgery, University of Toronto,Toronto, ON, Canada; and yPopulation Health Research Institute,McMaster University, Hamilton, ON, Canada.

Submitted May 9, 2008; accepted August 23, 2008.No benefits or funds were received in support of this study.Reprint requests: Rajiv Gandhi, MD, Toronto Western

Hospital, East Wing 1-439, 399 Bathurst St, Toronto, ON, CanadaM5T 2S8.

© 2009 Elsevier Inc. All rights reserved.0883-5403/08/2407-0003$36.00/0doi:10.1016/j.arth.2008.08.004

1015

infection would save the patient significant morbid-ity and the health care system significant costs.

Prophylactic use of antibiotic-laden bone cement(ALBC) has been proposed to decrease the incidenceof deep infections [11,12]. In a survey of 1015American arthroplasty surgeons, only 56% usedALBC routinely because there lacks sufficientevidence to validate its use in primary kneearthroplasty at this time [7,9,13].

Our primary objective was to determine if theprophylactic use of ALBC decreases the deepinfection rate as compared to plain bone cement(PBC) after primary TKA at 1 year of follow-up.

Methods

Study patients were recruited from a singleCanadian academic institution, the TorontoWesternHospital, prior to undergoing primary knee replace-ment surgery between the years of 1998-2006. Ourinclusion criteria for the study were ages 18 andolder and a diagnosis of primary or secondaryosteoarthritis or rheumatoid arthritis. Patients wereexcluded if they had a prior history of knee sepsis.

Table 1. Unadjusted Analysis Comparing Demographicand Baseline Functional Data between Groups

Plain Cement(n = 811)

Abx Cement(n = 814) P

ean Age (SD) 67.2 (10.8) 65.1 (15.4) .13ean BMI (kg/m2) 30.7 (7.2) 30.5 (6.8) .74Men 33.0% 35.1% .39Higher education 47.1% 44.1% .35Rheumatoid arthritis 17.4% 16.0% .39

harlson Index (%)0 56% 59% .531 28% 25%2 11% 11%≥3 5% 5%reoperative WOMAC scoresOMAC total 54.0 (18.7) 52.1 (16.9) .06OMAC pain 11.2 (4.0) 10.8 (3.6) .09OMAC function 45.3 (16.1) 43.7 (14.5) .07

1016 The Journal of Arthroplasty Vol. 24 No. 7 October 2009

All patients gave informed consent to participate inthe study. All data were collected by an independentassessor not involved in the medical care of thepatients. The study protocol was approved by thehuman subject review committee.All surgeries were performed by 1 of 3 fellowship-

trained arthroplasty surgeons, 2 of whom routinelyuse ALBC, whereas the other surgeon uses PBC.Surgical technique was similar between the 3 sur-geons, including use of tourniquet, operating roomwith laminar air flow, and implants used. All patientsin both groups received a standard protocol of 1 doseof systemic antibiotics preoperatively and for 24 hafter surgery. For the ALBC group, Simplex T(Stryker, StrykerCanada,Hamilton,Ontario, Canada;tobramycin impregnated) cement was used and plainSimplex P (Stryker) cement in the other group.Deep infection was defined as per the Centre of

Disease Control for surgical site infection [14] as:

• occurring within 30 days of procedure or 1 yearin the case of implants

• related to the procedure• involving deep soft tissues such as the fascia,muscles, or jointsplus

at least one of the following criteria:

• purulent drainage from the incision• a deep incision spontaneously dehisces or isdeliberately opened by a surgeon when thepatient has at least one of the following signs orsymptoms—fever (N38°C), localized pain, ortenderness—unless the culture is negative

• an abscess or other evidence of infectioninvolving the incision is found on directexamination or by histopathologic or radiologi-cal examination

• a diagnosis of a deep incisional surgical siteinfection by a surgeon or attending physician

Collection of Data

Baseline demographic data of age, sex, and bodymass index (BMI) were prospectively collected.Education was recorded as either higher educationlevel (university or above) or low education level(high school or below). Baseline medical health wasscored on the Charlson Comorbidity Illness Index[15]. Given the low incidence of comorbidity in thissample, the data were collapsed in 4 categories—ascore of 0, 1, 2, or 3 and above. Functional status andpain levelwere assessed preoperatively, and at 1 yearof follow-up with the Western Ontario McMasterUniversity Osteoarthritis Index (WOMAC) functionand pain scores, respectively [16]. A greater score on

the WOMAC scale represents poorer function orgreater pain. The psychometric properties of theWOMAC score with respect to reliability, validity,and responsiveness have beenwell established in theliterature [16].

Statistical Analysis

Continuous data such as age, BMI, and WOMACpain and function scores were compared betweengroups using t tests. Means and SDs are reported forall continuous variables. Categorical data such assex, education, Charlson Index, diagnosis, andincidence of infection are reported with frequenciesand groups were compared with the χ2 test.

Multivariate linear regression modeling was per-formed to determine the impact of ALBC on theincidence of deep infection. The covariates enteredinto the model were age, BMI, sex, diagnosis,education, preoperative WOMAC total score, andCharlson Index.

The sample size was calculated to detect a 50%difference in the deep infection rate at 1-yearfollow-up between the patients treated with ALBCcompared to PBC, assuming a 3% incidence of deepinfection. Therefore, to detect an effect size of 0.5,with a type I error of 5%, and 80% power, werequire a total sample size of 1534 patients.

All statistical analysis was performed with SPSSversion 13.0 (Chicago, Ill). β-Coefficients for regres-sion modeling and their 95% confidence intervals(CI) are reported. All reported P values are 2-tailedwith an α of .05.

Results

In our study cohort of 1625 consecutive patients,811 (49.9%) had their knee replacement with ALBCand 814 (50.1%) with PBC. We had 85% to 95%

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Table 2. Unadjusted Analysis Comparing Outcome DataBetween Groups

Plain Cement(n = 811)

Abx Cement(n = 814) P

1 y WOMAC scoresWOMAC total 26.8 (17.9) 26.8 (17.8) .92WOMAC pain 5.5 (3.6) 5.2 (3.7) .29WOMAC function 22.2 (14.5) 22.4 (14.8) .85Deep infection (%) 25 (3.1%) 18 (2.2%) .27

Antibiotic Cement and Deep Knee Infection � Gandhi et al 1017

complete data for all demographic variables andfunctional outcome scores. We had complete dataon the incidence of deep infection.At the time of surgery, there were no differences

between groups for age, sex, BMI, education,diagnosis, or Charlson Index (P N .05). There wasa trend towards greater preoperative WOMAC pain(P = .09) and function (P = .07) scores in the plaincement group (Table 1).The deep infection rate in the ALBC group was

2.2% (18/814) and 3.1% (25/811) in the PBC group(P = .27). The overall infection rate was 2.6% (43/1645) at 1 year of follow-up. There were nodifferences in WOMAC scores between groups at1 year of follow-up.(P N .05, Table 2).Adjusted analysis showed that the use of ALBC

was not predictive of a lower incidence of deepinfection at 1 year (P = .84). A greater score on theCharlson Index showed a strong trend to predictingdeep infection (P = .05, Table 3).

Table 3. Linear Regression Model Predicting Deepnfection by Antibiotic Cement, Age, Sex, BMI, Charlsonndex, Education, Diagnosis of Rheumatoid Arthritis and

Preoperative Total WOMAC Score

Odds Ratio(95% Confidence Interval) P

ntibiotic cement 1.1 (0.4,3.1) .85ge 1.0 (0.9,1.0) .57ex 0.7 (0.3,2.1) .56MI 1.0 (0.9,1.1) .50harlson Index 1.8 (1.0,3.2) .05ducation 1.3 (0.4,3.6) .67reoperative WOMAC 1.0 (0.9,1.0) .94heumatoid arthritis 0.5 (0.1,2.0) .31

Discussion

Overall, we report a 2.6% deep infection rate at 1year of follow-up in our cohort of primary,cemented TKA. The use of ALBC did not reducethe incidence of deep infection as compared to theuse of PBC.In 2 prospective randomized trials, Chiu et al

reported that cefuroxime-impregnated bone cementwas effective in preventing deep knee infectionfollowing total knee arthroplasty [12], particularlyin those with diabetes [11]. In both studies, theauthors did not report if the treating surgeons oroutcome assessors were blinded to the treatmentallocation. Moreover, the randomization sequencewas based on even and odd hospital record numbersrather than a more appropriate method such ascomputer generated random numbers. Both studiesexcluded patients who have had previous kneesurgery and those with peripheral vascular disease,which limits the generalizability of their findings.Compared with the cost of PBC, ALBC costs

between US $284 to $349 greater per 40-g package

[17]. Jiranek et al [17] estimated that the deepinfection rate would need to be reduced from 1.5%to 0.3% to recover the costs associated with theroutine use of low-dose antibiotic bone cement inprimary joint arthroplasty. This represents a relativerisk reduction of 5 times, which we did not see inour study.

Increased infection rates among certain high-riskpopulations have been described by many authors.Amongst diabetic patients, various authors havereported infection rates between 3.1% and 13.5% inpatients undergoing primary joint arthroplasty[11,18-20]. Infection rates in rheumatoid arthritispatients have been reported between 2% and 8% invarious studies [4-6]. Blom et al [21] reviewed theresults of 931 primary and 69 revision total kneereplacements and found the risk of deep infection tobe almost 6 times greater in revision surgery ascompared to primary knee arthroplasty. We foundthat a greater comorbidity predicted a higherincidence of infection and perhaps ALBC would bebeneficial in this high-risk group.

In considering the use of ALBC, the potential risksof toxicity, allergic reactions, drug-resistant organ-isms, and decreased mechanical strength of thecement must be considered. Two authors havesuggested a potential for an increase in drug-resistant organisms with the use of prophylacticantibiotic bone cement and therefore advised limit-ing its use to only high-risk populations [13,17]. Toour knowledge, there have not been any reports oftoxicity or allergy attributed to the use of ALBC [2].Biomechanical testing has shown that, in contrast tothe use of high-dose antibiotics which can weakenbone cement [22,23], the low-dose antibiotic-impregnated bone cements have negligible reduc-tions in fatigue strength, and implant fixation is notcompromised [24-27].

Our study had sufficient sample size to detect aclinically meaningful difference if it existed. Thepotential limitation of our study is its nonrando-mized design. We have measured many potential

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1018 The Journal of Arthroplasty Vol. 24 No. 7 October 2009

confounders and used regression modeling tech-niques to adjust for their effects on our outcomeof interest. Thus, we feel our results remain validand generalizable.In summary, our results indicate that ALBC did

not significantly reduce the incidence of deep kneeinfection after primary TKA. Further study isrequired to investigate the efficacy of ALBC in theabove-defined high-risk groups and to perform acost analysis for the use ALBC in primary TKA.

Acknowledgment

The authors thank Peggy Tso for her assistancewith data collection and management for this study.

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