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The Value of Intraoperative Gram Stain in Revision Total Knee Arthroplasty
Patrick M. Morgan, MD1; Peter Sharkey, MD2; Elie Ghanem, MD2; Javad Parvizi, MD, FRCS2; John C. Clohisy, MD1; R. Stephen J. Burnett, MD, FRCS(C)1; Robert L. Barrack, MD1
1 Department of Orthopaedic Surgery, Washington University School of Medicine, One Barnes-Jewish Hospital Plaza, 11300 West Pavilion, St. Louis, MO 63110. E-mail address for R.L. Barrack: barrackr@wustl.edu
2 Rothman Institute of Orthopaedics, Thomas Jefferson University Medical School, 925 Chestnut Street, Philadelphia, PA 19107
View Disclosures and Other Information
Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from Stryker Orthopaedics, Smith and Nephew Orthopaedics, and the Orthopaedic Foundation at the Rothman Institute. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. A commercial entity (Stryker Orthopaedics) paid or directed in any one year, or agreed to pay or direct, benefits in excess of $10,000 to a research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which one or more of the authors, or a member of his or her immediate family, is affiliated or associated.
Investigation performed at the Washington University School of Medicine, St. Louis, Missouri, and Thomas Jefferson University Medical School, Philadelphia, Pennsylvania

The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2009 Sep 01;91(9):2124-2129. doi: 10.2106/JBJS.H.00853
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Abstract

Background: The accurate preoperative diagnosis of infection is an essential component of decision-making prior to revision total knee arthroplasty. When preoperative modalities used to detect infection reveal equivocal findings, the surgeon may rely on intraoperative testing. While intraoperative Gram stains are routinely performed during revision total knee arthroplasty, their value remains unclear.

Methods: We retrospectively reviewed the records on 945 revision total knee arthroplasties performed at three university institutions to which patients were referred for total joint arthroplasty; the results of an intraoperative Gram stain were available for review in 921 cases (97.5%). Of these knees, 247 were classified as infected on the basis of (1) the presence of the same organism in two cultures; (2) growth, on solid media, of an organism as well as other objective evidence of infection; (3) histologic evidence of acute inflammation; (4) gross purulence; and/or (5) an actively draining sinus. We reviewed the results of preoperative laboratory studies, which included measurements of the erythrocyte sedimentation rate, C-reactive protein values, and white blood-cell count in 90%, 76%, and 98% of cases, respectively. Preoperative aspiration to obtain a specimen for culture and a cell count was performed routinely at one center and selectively at the other two centers, and the results were available for review in 439 (48%) of the 921 cases.

Results: Intraoperative Gram staining was found to have a sensitivity of 27% and a specificity of 99.9%. The positive and negative predictive values were 98.5% and 79%, respectively. The test accuracy was 80%. Patients with a true-positive Gram stain had a significantly higher preoperative white blood-cell count, C-reactive protein level, and nucleated cell count in the aspirate when compared with patients with a false-negative Gram stain (p < 0.001). In no case did the results of the intraoperative Gram stain alter treatment.

Conclusions: The intraoperative Gram stain was found to have poor sensitivity and a poor negative predictive value, and its results did not alter the treatment of any patient undergoing revision total knee arthroplasty because of a suspected infection. These data do not support the routine use of intraoperative Gram staining in revision total knee arthroplasty; instead, they suggest a much more limited role for this test.

Level of Evidence: Diagnostic Level I. See Instructions to Authors for a complete description of levels of evidence.

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    References

    Accreditation Statement
    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    Robert L. Barrack, MD
    Posted on December 03, 2009
    Dr. Barrack and colleagues respond to Drs. Liao and Lin
    Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, Missouri

    We would like to thank the letter writers for their interest in our study, “The Value of Intraoperative Gram Stain in Revision Total Knee Arthroplasty.” We apologize for the error in Table I; the correct number in the last column should be 154 rather than 142. This was an error in the editing process that had no effect on any of the statistical analysis. There are obviously differences of opinion regarding the statistical tests utilized and statistical terminology. To resolve these differences, we submitted the manuscript, the letter, and the raw data to the University of Minnesota Biostatistics Design and Analysis Center. The responses that follow are based on their analysis and conclusions.

    The letter writers’ suggestion that intraoperative Gram stain may be at least as good as any one pre-operative test (when evaluated individually) is an initially intuitive but ultimately misleading method of evaluating the data. As has been shown by multiple authors (1-3), preoperative infection studies (ESR, CRP, cell count and differential of aspirated fluid) should not be interpreted individually, but should instead be used together when evaluating a patient for periprosthetic infection (PPI). When used in combination, these studies have been shown to have both excellent sensitivity and specificity and remain, for this reason, the essential diagnostic tool for the revision total joint surgeon. As previous authors have shown (2,4-5), the intra-operative Gram stain is a particularly poor study for investigating an arthroplasty for infection and, though it adds nothing to the preoperative workup, it does add additional cost and potentially more operative time in waiting for urgent Gram stain results. In terms of our sample of patients, we used a large, multi-center registry that included all revision total knee arthroplasties performed over a set period of time. One center obtained pre-operative aspiration routinely while it was used selectively at the other two. This sample method, though imperfect, is as free of implicit or explicit bias as is possible when using a multi-center registry. We found no strong argument for replacing the familiar and interpretable measures of sensitivity, specificity, and positive/negative predictive value (SSPNPV) with the letter writers’ suggested methods. The Youden index (sensitivity + specificity -1) is unable to differentiate between high sensitivity/poor specificity and poor sensitivity/high specificity and in the investigation for PPI we would suggest that knowing a study’s actual sensitivity and specificity is therefore preferable. In the context suggested, the diagnostic odds ratio is difficult to interpret and appears misleading (a diagnostic odds ratio of 250 for a test with poor sensitivity and high specificity); we question its appropriateness when compared to the more standard SSPNPV. Similarly, we have reservations in applying accuracy to the event of PPI without a mechanism in place for correcting for agreement-by-chance. The Youden index is used even more rarely than the diagnostic odds ratio in the orthopaedic literature, probably for the reasons noted and certainly there is no basis to favor these tests over the SSPNPV analysis presented in the paper.

    Finally, the suggestion that the Mann-Whitney U test is favored over the Mann-Whitney t test with Gaussian approximation or that decision matrix is more appropriate than Chi-square is a distinction without a difference. In both cases these are minor differences in terminology that have no impact on the statistical analysis.

    In summary, there is currently no basis to support an increased use of intra-operative Gram stain for the diagnosis of periprosthetic infection. The Gram stain, while of great historical interest, has numerous inherent problems including sampling error and tremendous operator dependence both in performing and interpreting the test. This is compounded by the fact that it is frequently utilized intraoperatively where time pressures can introduce even more variability. The existing literature, including this study, supports care and caution in utilizing this test for clinical decision-making. Diligent performance and interpretation of a full set of preoperative serologic tests and examination of aspirated fluid in most cases is essential when treating the failed total knee arthroplasty. When this is done, the remaining role of the Gram stain is extremely limited.

    References

    1. Della Valle CJ, Sporer SM, Jacobs JJ, Berger RA, Rosenberg AG, Paprosky WG. Preoperative testing for sepsis before revision total knee arthroplasty. J Arthroplasty. 2007;22(6 Suppl 2):90-3.

    2. Spangehl MJ, Masri BA, O’Connell JX, Duncan CP. Prospective analysis of preoperative and intraoperative investigations for the diagnosis of infection at the sites of two hundred and two revision total hip arthroplasties. J Bone Joint Surg Am. 1999;81:672-83.

    3. Ghanem E, Parvizi J, Burnett RS, Sharkey PF, Keshavarzi N, Aggarwal A, Barrack RL. Cell count and differential of aspirated fluid in the diagnosis of infection at the site of total knee arthroplasty. J Bone Joint Surg Am. 2008;90:1637-43.

    4. Chimento GF, Finger S, Barrack RL. Gram stain detection of infection during revision arthroplasty. J Bone Joint Surg Br. 1996;78:838-9.

    5. Della Valle CJ, Scher DM, Kim YH, Oxley CM, Desai P, Zuckerman JD, Di Cesare PE. The role of intraoperative Gram stain in revision total joint arthroplasty. J Arthroplasty. 1999;14:500-4.

    Yuan-Ya Liao
    Posted on November 03, 2009
    More Evidence is Needed Before Abandoning Gram Stains
    Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan

    To the Editor:

    We read with interest but ended up with concern that Morgan et al. (1) have suggested the practice of routinely performing a Gram stain at the time of revision total knee athroplasty may safely be abandoned. The authors failed to recruit a consecutive sample of patients who underwent tests for white blood-cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and aspiration, and this introduces biases and jeopardizes the conclusion. From their data, we calculated the commonly used summary indices for diagnostic tests, accuracy, Youden index (2), and diagnostic odds ratio. The accuracies for Gram stain, WBC, ESR, CRP, and aspiration are 80.35%, 80.28%, 78.82%, 77.33%, and 66.74%, respectively. The Youden indices for Gram stain, WBC, ESR, CRP, and aspiration are 0.2698, 0.2731, 0.2731, 0.2677, and 0.2487, respectively. The diagnostic odds ratios for Gram stain, WBC, ESR, CRP, and aspiration are 250.45, 247.88, 247.88, 178.12, and infinity, respectively. The commonly used summary indices for Gram stain are not the most inferior ones and are superior to CRP. The positive likelihood ratio for Gram stain, 182.83, is the highest among the tests. The negative likelihood ratio for Gram stain, 0.73, is the same as the ones of WBC, ESR, and CRP. It goes without saying that the unstable predictive values, which are easily influenced by the disease prevalence, the negative and positive predictive values for Gram stain are not the lowest. The sensitivity of Gram stain is better than CRP (26.98%) and aspiration (24.87%). The specificity of Gram stain is also better than CRP (26.98%). It is still too early to abandon the Gram stain, especially while awaiting the results of bacterial culture, and the results of the Gram stain will help with selecting the proper empiric antibiotics. The results of Table III reflect the spectrum effect (3) and do not argue against the Gram stain.

    Lastly, there are several proofreading errors. First, in the 5th column of Table I, the total of aspiration does not add up, and the total of aspiration should be 427. Second, there exists the Mann-Whitney U test instead of a Mann-Whitney t test with Gaussian approximation. Third, the authors misused the term Chi-square analysis to describe a decision matrix.

    The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

    References

    1. Morgan PM, Sharkey P, Ghanem E, Parvizi J, Clohisy JC, Burnett RS, Barrack RL. The value of intraoperative Gram stain in revision total knee arthroplasty. J Bone Joint Surg Am. 2009;91:2124-9.

    2. Youden WJ. Index for rating diagnostic tests. Cancer. 1950;3:32-5.

    3. Mulherin SA, Miller WC. Spectrum bias or spectrum effect? Subgroup variation in diagnostic test evaluation. Ann Intern Med. 2002;137:598-602.

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