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T HE J OURNAL

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S URGERY, I NCORPORATED

Current Concepts Review

Culture-Negative Periprosthetic Joint Infection Javad Parvizi, MD, FRCS, Omer Faruk Erkocak, MD, and Craig J. Della Valle, MD Investigation performed at the Rothman Institute of Orthopaedics at Thomas Jefferson University, Philadelphia, Pennsylvania, and Midwest Orthopedics at Rush, Chicago, Illinois

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Negative results on culture still pose a real challenge in the diagnosis of periprosthetic joint infection.

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There are numerous reasons for the inability to isolate the infecting organism from the affected joint, the most important of which is the administration of antibiotics prior to obtaining culture samples.

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For patients suspected of having a periprosthetic joint infection, antibiotics should not be given until the diagnosis is confirmed or aspiration of the joint should be delayed for at least two weeks after the last dose of antibiotics.

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Other strategies that can be used to enhance the likelihood of obtaining a positive result on culture include expeditious transport of culture samples, placement of a tissue or fluid sample in the appropriate medium, implant sonication, and prolonging the incubation period of the samples to two or three weeks.

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In patients in whom the prerevision aspiration has not yielded an infecting organism, yet the clinical picture is consistent with periprosthetic joint infection, a minimum of three to five tissue culture samples are recommended at the time of revision surgery.

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Biomarkers and molecular techniques, such as polymerase chain reaction identification of bacterial DNA, may play an increasing role in the future in the diagnosis of periprosthetic joint infection, when standardized techniques have not identified an infecting organism.

Peer Review: This article was reviewed by the Editor-in-Chief and one Deputy Editor, and it underwent blinded review by two or more outside experts. The Deputy Editor reviewed each revision of the article, and it underwent a final review by the Editor-in-Chief prior to publication. Final corrections and clarifications occurred during one or more exchanges between the author(s) and copyeditors.

Periprosthetic joint infection is one the most devastating complications of joint arthroplasty. Although periprosthetic joint infection is an infrequent complication with a reported prevalence of 1% to 2% in the United States, it is the most common indication for revision total knee arthroplasty in the Medicare population1 and the third most frequent indication for revision total hip arthroplasty 2. Moreover, the prevalence of periprosthetic joint infection appears to be on the rise, with a projected number exceeding 60,000 to 70,000 patients in the United States by 20203.

Diagnosis of periprosthetic joint infection relies on a detailed history and physical examination combined with serologic tests and a review of radiographs4-6. In addition, isolation of the infecting organism from cultures of fluid or tissue obtained from the affected joint is critical for the selection of appropriate antibiotic therapy and provides some insight into prognosis5. According to the recent definition of periprosthetic joint infection as proposed by the Musculoskeletal Infection Society, the isolation of the same pathogen from two separate tissue or fluid samples obtained from within the joint is diagnostic of periprosthetic

Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. One or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

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joint infection7. However, in 7% to 12% of patients, cultures are negative despite the presence of other clear indicators of infection such as a draining sinus or a highly elevated synovial fluid white blood cell (WBC) count and differential8-13. Falsely negative cultures not only pose a challenge for selecting appropriate antimicrobial therapy but also are often a source of anxiety for both the patient and the surgeon who may question the diagnosis because of the inability to identify the pathogen. Management of culture-negative periprosthetic joint infection involves the administration of broad-spectrum antibiotics or multiple antibiotics against the most common infecting organisms. This approach places the patient at risk of systemic toxicity and may not provide coverage against fungi or rare organisms. It is critical that every effort be made to isolate the infecting organism. Causes of Culture-Negative Periprosthetic Joint Infection The prevalence of culture-negative periprosthetic joint infection has been reported to range between 7% and 12%8-13. Previous studies have highlighted some of the potential causes for an inability to isolate the infecting organism. The most important cause is administration of antibiotics to patients prior to obtaining fluid or tissue samples from the affected joint14. Trampuz et al. demonstrated that any use of antibiotics in the two weeks before obtaining culture samples was associated with a lower yield of cultures15. In another report of sixty patients with culture-negative periprosthetic joint infection, Berbari et al. found that 53% of patients with culture-negative periprosthetic joint infection had received antimicrobial therapy before culture samples were obtained from the affected joint8. Discontinuing antimicrobial therapy for a minimum of two weeks prior to surgical intervention or culture, if it can be done safely, is advisable to improve the sensitivity of periprosthetic tissue cultures; for certain fastidious organisms that are difficult to culture, even longer periods of time may be required8,15-19. Further, the administration of antibiotics prior to making the diagnosis and obtaining synovial fluid from the joint may affect the accuracy of the synovial fluid WBC count and differential, which are powerful tests commonly used to diagnose periprosthetic joint infection4,5,8,15. Finally, it has been demonstrated that postoperative wound drainage after index arthroplasty that is prolonged (beyond five days) was also associated with an increased risk of negative cultures among patients with periprosthetic joint infection20 most likely caused by the use of antibiotics for draining wounds. Culture techniques may prevent the identification of the infecting organism. One cause of culture-negative periprosthetic joint infection is the failure of traditional tissue cultures to recover infecting organisms encapsulated in a biofilm. The organisms in a biofilm are encapsulated in a complex structure composed of macromolecules such as glycocalyx that allow the organisms to evade the host’s immune system (macrophages and neutrophils)21,22. It has been estimated that these sessile bacteria are 1000 times more resistant to antibiotics than their planktonic (freefloating) counterparts23-25. In chronic periprosthetic joint infection, most of the microorganisms exist in a biofilm, attached

to the implant surface and surrounding tissues. The latter explains the low yield of culture in these patients, as culture relies on isolation of planktonic organisms26. The absence of free-floating bacteria also explains the paucity of inflammatory signs in chronic periprosthetic joint infection. A second reason for not obtaining a positive culture in a patient with a suspected periprosthetic joint infection is the failure to use specialized culture mediums for growth and isolation in the laboratory. Atypical organisms, such as fungi and mycobacteria, do not grow on routine aerobic or anaerobic media, and organisms such as Propionibacterium acnes and some coagulase-negative staphylococci need one to two weeks for isolation27-30. A third reason for failed cultures is the method of obtaining culture samples and the transfer of the samples to the laboratory. Samples taken from noninfected areas of the joint, delaying the transport of the samples and allowing the tissue to dehydrate, or exposure to extremes of temperature can affect the yield of cultures31. A fourth reason for decreasing the yield from aspiration of the joint is the introduction of bacteriostatic compounds, such as saline solution or local anesthetic, into the joint cavity at the time of aspiration16. If, at the time of attempted aspiration, no fluid is obtained, we recommend a second attempt at aspirating the joint on another occasion. Intraoperatively, irrigation of the open wound with bacteriostatic agents prior to obtaining the culture samples can also interfere with isolation of the infected pathogen5,32,33. Strategies to Improve Pathogen Identification in Patients with Negative Cultures (Table I) The American Academy of Orthopaedic Surgeons (AAOS) Clinical Practice Guideline on the Diagnosis of Periprosthetic Joint Infections of the Hip and Knee strongly recommends against the administration of antibiotics to patients with suspected periprosthetic joint infection until the diagnosis is confirmed or refuted34. As previously discussed, this is the most effective way to reduce the prevalence of culture-negative periprosthetic joint infection35. This same guideline also contains a recommendation to withhold antibiotics for at least two weeks prior to obtaining cultures from the joint, although longer antibiotic-free periods may be required for some organisms that are difficult to culture. It is important to distinguish, however, between therapeutic and prophylactic antibiotic administration given prior to revision surgery. While it is clear that the use of therapeutic antibiotics prior to obtaining deep joint cultures is to be discouraged, the role of prophylactic antibiotics given prior to revision surgery as a cause of culture-negative periprosthetic joint infection is less clear. The routine use of prophylactic antibiotics is considered standard for total joint arthroplasty as a powerful means to prevent periprosthetic joint infection. However, traditional teaching has suggested that these antibiotics be withheld prior to revision surgery for fear that results of deep cultures would be affected. Two recent studies have challenged this notion13,36, suggesting that a single dose of prophylactic antibiotics

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TABLE I Strategies to Minimize the Rate of Culture-Negative Periprosthetic Joint Infection Preoperative d

Administration of antibiotics to patients should be avoided until the diagnosis of periprosthetic joint infection has been confirmed or refuted

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Aspiration of the joint should be delayed for at least two weeks after the last dose of administered antibiotic

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If cultures from the first aspiration were negative, a repeat aspiration of the joint should be considered and the strategies outlined in general considerations section should be used

Intraoperative d

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Multiple (three to five) culture samples should be obtained from deep regions of the joint (intramedullary canal and prosthesis-bone interface are thought to be most representative and have potential for high yield) The tissue culture samples should be transferred to sterile transport bottles using clean instruments and without allowing samples to come into contact with gloves or draping Preoperative antibiotics should be withheld if infecting organism has not been isolated preoperatively Tissue culture samples should be obtained prior to irrigating the wound or deeper tissues

does not affect culture yield that is measureable with contemporary techniques. Further, as our ability to preoperatively ‘‘rule in’’ or ‘‘rule out’’ infection has improved, the practice of withholding prophylactic antibiotics has come under further scrutiny. Specifically, the AAOS Clinical Practice Guideline on the diagnosis of periprosthetic joint infection recommends determination of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level in all patients prior to revision surgery as these are highly sensitive tests. If these serologic markers are negative, the risk of periprosthetic joint infection is very low and hence the risks of withholding antibiotics appears greater than any small effect that prophylactic antibiotics would have on intraoperative cultures. Similarly, if the ESR and CRP level are elevated, or the clinical suspicion for infection is high, the joint would be aspirated preoperatively and a synovial fluid WBC count and differential will rule in or out infection in the majority of patients. In addition, a culture of that fluid may also confirm the diagnosis and identify the infecting organism. Thus, the available evidence suggests that patients undergoing revision arthroplasty for aseptic failure and patients with known periprosthetic joint infection, in whom the infecting organism is preoperatively identified, should receive prophylactic preoperative antibiotics. The only patients in whom preoperative antibiotics should be withheld are those in whom periprosthetic joint infection is strongly suspected but no organism is isolated. At the time of revision surgery, the surgeon should obtain multiple cultures from within the joint as is recommended by the AAOS Clinical Practice Guideline on the diagnosis of periprosthetic joint infection. Obtaining tissue from the intramedullary canal or from the bone-implant interface is thought to carry a better yield for isolation of organisms37, and the direct culture of synovial fluid or tissue provides better yield than do

General Considerations d

Transferring part of the joint fluid into blood culture bottles as well as standard culture bottles should be considered

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Expeditious transport of the culture bottles to the microbiology laboratory should be arranged

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The microbiology laboratory should be contacted to provide information about the patient and to discuss the potential for the use of enriched or specialized medium

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The microbiology laboratory should be instructed to hold the culture samples for 14 and possibly 21 days, if an organism is not isolated at an earlier time point

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Use of the Ibis T5000 (Ibis Biosciences) or emerging molecular technologies to isolate the infecting organism should be considered

swabs10. The tissue should be dissected free with a sharp instrument and not cauterized, as extreme heat is likely to cause tissue necrosis and interfere with isolation of the infecting organism31. Samples should be taken using clean instruments and transferred directly into the culture receptacle without allowing the samples to come into contact with gloves, drapes, or other surfaces. The latter strategy is likely to be effective in reducing the occurrence of false-positive cultures and ensuring that the true infecting organism is isolated. Techniques for cultures are specific. Tissue or fluid samples obtained from the joint should be properly and immediately processed. Blood culture flasks improve the detection of microorganisms from synovial fluid specimens and decrease contamination compared with conventional agar or broth methods32. Synovial fluid inoculated in blood culture flasks more frequently identified the infecting microorganism with a greater sensitivity and specificity for diagnosis10. If fungal or mycobacterial infection is suspected, the proper transport (sterile screw-cap tubes, Amies transport medium, or Stuart transport medium) and isolation media (Lowenstein-Jensen growth medium, Sabouraud agar, or brain-heart infusion agar) should be used38-40. Some authorities also propose the use of an enriched medium for all cultures such as trypticase soy agar containing sheep blood, chocolate agar, McConkey agar, or brain-heart infusion broth41-43. Another strategy to improve culture yield is to prolong the period of incubation of culture samples for fourteen and possibly twenty-one days44. The strategy should be to plan to keep the culture samples for fourteen days unless the infecting organism is not isolated, in which case the incubation should be extended to twenty-one days to allow isolation of slow-growing organisms such as Mycobacterium species and some fungi. The isolated agents can be divided into two groups according to their

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isolation time: an early population found predominantly within the first week of culture and a late population detected predominantly during the second week44. Although fourteen days of incubation has been recommended for all routine culture samples by some authorities44, we believe this should be reserved for cases in which an organism is not identified preoperatively after a more standard incubation period44-46. Sonication of the retrieved prosthesis is one method for biofilm disruption to expose the infecting organism and improve the yield of culture14,15. Sonication increases the chemical degradation of particles as well as destruction and permeability of the bacterial wall. It has been shown to preserve microbial viability47,48. Sonication of retrieved implants is reported to have higher sensitivity than conventional techniques15,49-52. The advantages include its simplicity, reproducibility, and efficacy in improving yield for the isolation of organisms and antimicrobial susceptibility testing. The limitation of this technique is its availability. Novel Molecular Techniques for Isolation of an Infecting Organism In recent years, there have been immense advances in the field of molecular biology in general and biomarkers in particular. Biomarkers are either by-products of infecting organisms or immune cells that are activated as a result of infection. We recently reported on the use of leukocyte esterase strips in detecting periprosthetic joint infection53. The leukocyte esterase test had 100% specificity and 100% positive predictive value for diagnosis of periprosthetic joint infection. The utility of this simple and inexpensive test has been confirmed54, although it can be affected by blood or other debris in the joint that make it difficult to read and the colorimetric nature of the test makes it somewhat subjective to interpret. These cohorts included culturenegative periprosthetic joint infections that were accurately identified using the leukocyte esterase strips. There have also been reports of measuring the CRP level or other biomarkers in the synovial fluid of patients suspected of having a periprosthetic joint infection55,56. The downside of using a proxy biomarker is the inability to identify the infecting organism, and thus there is no avenue for antibiotic susceptibility testing to guide antibiotic treatment. Polymerase chain reaction (PCR) is a biochemical technology that amplifies DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence57. It has been an exciting development as a potential method for the detection of periprosthetic infections58. There are multiple PCR-based techniques available that use either species-specific primers51 or broader-range primer pairs to 16S ribosomal RNA (16S rRNA)59-66. PCR-based assays have yielded good results and have been suggested as an alternative that might eliminate the high false-negative rates of synovial fluid culture59,61-63,66. Although PCR-based assays increased the sensitivity of cultures in culture-negative cases, in practical use, the technique has been limited by a number of factors, including a high rate of false-positive cultures, technical equipment requirements, and cost67,68. The extreme sensitivity, due to the persistence of

bacterial DNA after cell death or bacterial contamination in the recombinantly prepared reagents69, is presumably the most important reason for the high rate of false-positive results and subsequent failure of clinicians to embrace this technology in the clinical arena. To improve the specificity of these molecular techniques and reduce the number of false-positive results, RNA-based PCR methods have been described60,62,65,69. Theoretically, an RNA-based method would be preferable as RNAs are more labile and would be associated primarily with living bacteria. It has been reported that the use of messenger RNA (mRNA)-based PCR nearly eliminated the false-positive results that may have occurred because of the detection of nonviable genomic DNA70. However, naturally low amounts of mRNA transcripts in the bacteria (95% of total RNA content), specificity close to 100%, and sensitivity equivalent to that of intraoperative cultures69. Specific primers targeting the mecA gene of methicillin-resistant Staphylococcus aureus (MRSA) have also been developed and have yielded promising results71,72. More recently, we utilized an Ibis T5000 biosensor (Ibis Biosciences, Carlsbad, California), a multiplex PCR-based technology, which employs multiple pairs of species-specific primers rather than universal primers to amplify regions of an organism’s genome and may be used to improve the diagnosis of culturenegative periprosthetic joint infection by allowing identification of the infecting organism73. Identification of the resistance gene using this technology promises differentiation among patients with an infection and culture-positive results, patients with an infection and culture-negative results, and patients without an infection who are suspected of having a periprosthetic joint infection. Another intriguing technology is PLEX-ID (Abbott Laboratories, Abbott Park, Illinois), that similarly relies on targeted electrospray technology to identify the infecting organism among 3100 recognized species74. The device is capable of characterizing the infecting organism using high-resolution subtyping and the drug resistance profile, including the mecA gene that is indicative of methicillin resistance. Falsely Positive Cultures While the focus of this review is culture-negative periprosthetic joint infection, false-positive cultures are equally important to recognize. It is clear that traditional cultures, while still considered by some to be the so-called gold standard for diagnosis, have serious limitations as previously outlined. To decrease the risk of false-positive culture results, handling of the tissue samples to be cultured is critical. Specifically, clean instruments should be utilized intraoperatively and the tissue obtained transferred directly into a sterile culture vial or cup, without coming into contact with gloves, drapes, or gowns. It is important to recognize that one individual culture result should not be interpreted without considering the other diagnostic tools available to the clinician. The AAOS Clinical

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Practice Guideline includes a strong recommendation for serologic testing prior to revision surgery followed by an aspiration of the joint if serum tests are abnormal, and hence most patients with a periprosthetic joint infection should be identified preoperatively. Specifically, if the ESR and CRP level are both normal, the risk of infection would be low and the culture result, if positive, suspect. Furthermore, if the serologic test results were abnormal, the joint would have been aspirated preoperatively and the clinician would have a synovial fluid WBC count and differential (as well as a preoperative culture) to interpret; if all of those tests were negative, infection is unlikely. Histopathologic examination of periprosthetic tissue is another valuable tool for the diagnosis of periprosthetic joint infection and can also help the clinician to place what may be considered a false-positive culture into an appropriate context. Further, the AAOS Clinical Practice Guideline strongly recommends that multiple cultures be obtained intraoperatively. If three to five cultures are obtained, it greatly facilitates culture interpretation, particularly if only one culture is positive while the others are all negative. Finally, an infectious disease specialist can be invaluable in helping to determine whether a culture is falsely positive. A Practical Approach to the Patient with a Suspected Culture-Negative Periprosthetic Joint Infection When the clinician is faced with a patient for whom the history, physical examination, serological findings, and analysis of synovial fluid suggest infection, but initial cultures from a preoperative aspiration are negative, the following steps may be helpful. First, the joint aspiration should be repeated, ensuring that the patient has not taken any antibiotics for at least two weeks. The fluid obtained should be sent for aerobic and anaerobic cultures as well as cultures specifically for fungi and for acid-fast bacilli. Joint fluid obtained should also be sent in blood culture flasks. The samples should be transported to the laboratory directly and expeditiously and should be processed upon receipt. The surgeon should speak with the microbiology laboratory, which is often directed by an infectious disease specialist who can further assist with guiding extended incubation (fourteen to twenty-one days) and may suggest special media for culture. Finally, the clinician should always seek details in the history that may suggest infection with atypical organisms such as Coccidioides in patients who travel or live in areas that are endemic to such organisms. A blood test to detect the presence of such organisms may also be performed. If all of the above has been performed and an organism has still not been detected prior to revision surgery, preoperative consultation with an infectious disease specialist should be sought. This will allow the patient to have further confirmation of the diagnosis by another specialist and allow the infectious disease specialist not only to become familiar with the case preoperatively (which may facilitate decisions on antibiotic selection postoperatively) but also to help guide the management of cultures obtained at the time of surgery. During revision surgery in a patient with culture-negative periprosthetic joint infection, three to five tissue specimens from the most suspicious-appearing areas should be taken for culture

prior to administering systemic antibiotics. The retrieved tissue samples should be processed in an expedient manner as described above. Sonication of retrieved implants should be performed, if available. Five samples of tissue should be obtained for permanent section for histopathological analysis to further confirm the diagnosis of periprosthetic joint infection. In conclusion, culture-negative periprosthetic joint infection poses a challenge to clinicians and patients alike and may account for ‡10% of patients who have an infection at the site of an arthroplasty8-13. Administration of directed antibiotic therapy against the infecting organism is not possible in these patients, necessitating administration of broad spectrum treatment and at times administering multiple antibiotics that place the patient at increased risk of systemic toxicity. There are numerous reasons for the inability to isolate the infecting organism from the affected joint, the most important of which is the administration of antibiotics prior to obtaining a deep culture. The other reasons are the failure of traditional tissue cultures to recover infecting organisms encapsulated in a biofilm as well as the failure to use specialized culture media for growth and isolation when atypical organisms, such as fungi and mycobacteria, are suspected. The AAOS Clinical Practice Guideline states that patients suspected of having a periprosthetic joint infection should not be given any antibiotics until the diagnosis is confirmed or refuted. In addition, delaying the aspiration of the joint for at least two weeks following the last dose of an administered antibiotic may be another strategy to isolate the organism. In the presence of negative cultures and an inconclusive aspiration with a high suspicion of periprosthetic joint infection and elevated inflammatory markers, a repeat aspiration of the joint should be performed. There are numerous strategies that can be used to enhance the yield of culture, including expeditious transport of culture samples, cultivation under sterile conditions, placement of tissue or fluid sample in the appropriate medium, prolonging the incubation period of the samples, and the use of enriched and specialized media for atypical organisms such as fungi and mycobacteria. Enlisting the support of an infectious disease specialist can also be invaluable. n

Javad Parvizi, MD, FRCS Omer Faruk Erkocak, MD Rothman Institute of Orthopaedics at Thomas Jefferson University, 925 Chestnut Street, 2nd Floor, Philadelphia, PA 19107. E-mail address for J. Parvizi: [email protected] Craig J. Della Valle, MD Midwest Orthopedics at Rush, Rush University Medical Center, 1611 West Harrison Street, #300, Chicago, IL 60612-4861. E-mail address: [email protected]

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References 1. Kurtz SM, Ong KL, Lau E, Bozic KJ, Berry D, Parvizi J. Prosthetic joint infection risk after TKA in the Medicare population. Clin Orthop Relat Res. 2010 Jan;468(1):52-6. Epub 2009 Aug 08. 2. Ong KL, Kurtz SM, Lau E, Bozic KJ, Berry DJ, Parvizi J. Prosthetic joint infection risk after total hip arthroplasty in the Medicare population. J Arthroplasty. 2009 Sep;24(6)(Suppl):105-9. Epub 2009 Jun 02. 3. Kurtz SM, Lau E, Watson H, Schmier JK, Parvizi J. Economic burden of periprosthetic joint infection in the United States. J Arthroplasty. 2012 Sep;27(8) (Suppl):61: e1. Epub 2012 May 02. 4. Parvizi J, Ghanem E, Sharkey P, Aggarwal A, Burnett RSJ, Barrack RL. Diagnosis of infected total knee: findings of a multicenter database. Clin Orthop Relat Res. 2008 Nov;466(11):2628-33. Epub 2008 Sep 10. 5. Patel R, Osmon DR, Hanssen AD. The diagnosis of prosthetic joint infection: current techniques and emerging technologies. Clin Orthop Relat Res. 2005 Aug;(437):55-8. 6. Atkins BL, Athanasou N, Deeks JJ, Crook DW, Simpson H, Peto TE, McLardySmith P, Berendt AR; The OSIRIS Collaborative Study Group. Prospective evaluation of criteria for microbiological diagnosis of prosthetic-joint infection at revision arthroplasty. J Clin Microbiol. 1998 Oct;36(10):2932-9. 7. Workgroup Convened by the Musculoskeletal Infection Society. New definition for periprosthetic joint infection. J Arthroplasty. 2011 Dec;26(8):1136-8. 8. Berbari EF, Marculescu C, Sia I, Lahr BD, Hanssen AD, Steckelberg JM, Gullerud R, Osmon DR. Culture-negative prosthetic joint infection. Clin Infect Dis. 2007 Nov 1;45(9):1113-9. Epub 2007 Sep 26. 9. Parvizi J, Ghanem E, Menashe S, Barrack RL, Bauer TW. Periprosthetic infection: what are the diagnostic challenges? J Bone Joint Surg Am. 2006 Dec;88(Suppl 4):138-47. 10. Font-Vizcarra L, Garcı´a S, Martı´nez-Pastor JC, Sierra JM, Soriano A. Blood culture flasks for culturing synovial fluid in prosthetic joint infections. Clin Orthop Relat Res. 2010 Aug;468(8):2238-43. Epub 2010 Feb 17. 11. Duff GP, Lachiewicz PF, Kelley SS. Aspiration of the knee joint before revision arthroplasty. Clin Orthop Relat Res. 1996 Oct;(331):132-9. 12. Pandey R, Berendt AR, Athanasou NA; The OSIRIS Collaborative Study Group. Oxford Skeletal Infection Research and Intervention Service. Histological and microbiological findings in non-infected and infected revision arthroplasty tissues. Arch Orthop Trauma Surg. 2000;120(10):570-4. 13. Ghanem E, Parvizi J, Clohisy J, Burnett S, Sharkey PF, Barrack R. Perioperative antibiotics should not be withheld in proven cases of periprosthetic infection. Clin Orthop Relat Res. 2007 Aug;461:44-7. 14. Trampuz A, Piper KE, Hanssen AD, Osmon DR, Cockerill FR, Steckelberg JM, Patel R. Sonication of explanted prosthetic components in bags for diagnosis of prosthetic joint infection is associated with risk of contamination. J Clin Microbiol. 2006 Feb;44(2):628-31. 15. Trampuz A, Piper KE, Jacobson MJ, Hanssen AD, Unni KK, Osmon DR, Mandrekar JN, Cockerill FR, Steckelberg JM, Greenleaf JF, Patel R. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med. 2007 Aug 16;357(7):654-63. 16. Barrack RL, Jennings RW, Wolfe MW, Bertot AJ. The Coventry Award. The value of preoperative aspiration before total knee revision. Clin Orthop Relat Res. 1997 Dec;(345):8-16. 17. Mont MA, Waldman BJ, Hungerford DS. Evaluation of preoperative cultures before second-stage reimplantation of a total knee prosthesis complicated by infection. A comparison-group study. J Bone Joint Surg Am. 2000 Nov;82(11):1552-7. 18. Lonner JH, Siliski JM, Della Valle C, DiCesare P, Lotke PA. Role of knee aspiration after resection of the infected total knee arthroplasty. Am J Orthop (Belle Mead NJ). 2001 Apr;30(4):305-9. 19. Burnett RS, Kelly MA, Hanssen AD, Barrack RL. Technique and timing of twostage exchange for infection in TKA. Clin Orthop Relat Res. 2007 Nov;464:164-78. 20. Malekzadeh D, Osmon DR, Lahr BD, Hanssen AD, Berbari EF. Prior use of antimicrobial therapy is a risk factor for culture-negative prosthetic joint infection. Clin Orthop Relat Res. 2010 Aug;468(8):2039-45. 21. Zimmerli W, Waldvogel FA, Vaudaux P, Nydegger UE. Pathogenesis of foreign body infection: description and characteristics of an animal model. J Infect Dis. 1982 Oct;146(4):487-97. 22. Zimmerli W, Lew PD, Waldvogel FA. Pathogenesis of foreign body infection. Evidence for a local granulocyte defect. J Clin Invest. 1984 Apr;73(4):1191-200. 23. Costerton JW, Lewandowski Z, Caldwell DE, Korber DR, Lappin-Scott HM. Microbial biofilms. Annu Rev Microbiol. 1995;49:711-45. 24. Stewart PS, Costerton JW. Antibiotic resistance of bacteria in biofilms. Lancet. 2001 Jul 14;358(9276):135-8. 25. Donlan RM. Biofilms: microbial life on surfaces. Emerg Infect Dis. 2002 Sep;8(9):881-90. 26. Costerton JW. Biofilm theory can guide the treatment of device-related orthopaedic infections. Clin Orthop Relat Res. 2005 Aug;(437):7-11.

27. Neogi DS, Kumar A, Yadav CS, Singh S. Delayed periprosthetic tuberculosis after total knee replacement: is conservative treatment possible? Acta Orthop Belg. 2009 Feb;75(1):136-40. 28. Larson AN, Razonable RR, Hanssen AD. Capnocytophaga canimorsus a novel pathogen for joint arthroplasty. Clin Orthop Relat Res. 2009 Jun;467(6):1634-8. Epub 2008 Dec 09. 29. Zappe B, Graf S, Ochsner PE, Zimmerli W, Sendi P. Propionibacterium spp. in prosthetic joint infections: a diagnostic challenge. Arch Orthop Trauma Surg. 2008 Oct;128(10):1039-46. Epub 2007 Sep 15. 30. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med. 2004 Oct 14;351(16):1645-54. 31. Meermans G, Haddad FS. Is there a role for tissue biopsy in the diagnosis of periprosthetic infection? Clin Orthop Relat Res. 2010 May;468(5):1410-7. Epub 2010 Feb 04. 32. Hughes JG, Vetter EA, Patel R, Schleck CD, Harmsen S, Turgeant LT, Cockerill FR 3rd. Culture with BACTEC Peds Plus/F bottle compared with conventional methods for detection of bacteria in synovial fluid. J Clin Microbiol. 2001 Dec;39(12):4468-71. 33. Powles JW, Spencer RF, Lovering AM. Gentamicin release from old cement during revision hip arthroplasty. J Bone Joint Surg Br. 1998 Jul;80(4):607-10. 34. American Academy of Orthopaedic Surgeons. The diagnosis of periprosthetic joint infections of the hip and knee. Guideline and evidence report. 18 June 2010. http://www.aaos.org/Research/guidelines/PJIguideline.pdf. Accessed 2013 Dec 12. 35. Della Valle C, Parvizi J, Bauer TW, DiCesare PE, Evans RP, Segreti J, Spangehl M, Watters WC 3rd, Keith M, Turkelson CM, Wies JL, Sluka P, Hitchcock K; American Academy of Orthopaedic Surgeons. American Academy of Orthopaedic Surgeons clinical practice guideline on: the diagnosis of periprosthetic joint infections of the hip and knee. J Bone Joint Surg Am. 2011 Jul 20;93(14):1355-7. 36. Burnett RS, Aggarwal A, Givens SA, McClure JT, Morgan PM, Barrack RL. Prophylactic antibiotics do not affect cultures in the treatment of an infected TKA: a prospective trial. Clin Orthop Relat Res. 2010 Jan;468(1):127-34. Epub 2009 Aug 11. 37. McPherson EJ, Patzakis MJ, Gross JE, Holtom PD, Song M, Dorr LD. Infected total knee arthroplasty. Two-stage reimplantation with a gastrocnemius rotational flap. Clin Orthop Relat Res. 1997 Aug;(341):73-81. 38. Koneman EW, Roberts GDP. Practical Laboratory Mycology, 3rd Edition, Baltimore, Williams and Wilkins, 1985. 39. Pfyffer GE, Brown-Elliott BA, Wallace RJ Jr. Mycobacterium. General characteristics, isolation and Straining procedures. In: Murray PR, Bron EJ, Jorgensen JH, Pfaller MA, Yolken RH, editors. Manual of clinical microbiology. 8th ed. Washington, DC: ASM Press; 2003. p 532-59. 40. Koneman EW, Allen SD, Janda WM, Schreckenberger PC, Winn WC. The Color Atlas and Textbook of Diagnostic Microbiology. 5th ed. Philadelphia: JB Lippincott Co.; 1997. 41. Ortega-Andreu M, Rodriguez-Merchan EC, Aguera-Gavalda M. Brucellosis as a cause of septic loosening of total hip arthroplasty. J Arthroplasty. 2002 Apr;17(3):384-7. 42. Forbes BA, Sahm DF, Weissfeld AS. Brucella. In: Forbes BA, Sahm DF, Weissfeld AS, editors. Bailey & Scott’s diagnostic microbiology. 11th ed. St Louis, MO: Mosby; 2002. p 487-90. 43. Marculescu CE, Berbari EF, Cockerill FR 3rd, Osmon DR. Fungi, mycobacteria, zoonotic and other organisms in prosthetic joint infection. Clin Orthop Relat Res. 2006 Oct;451:64-72. 44. Sch¨afer P, Fink B, Sandow D, Margull A, Berger I, Frommelt L. Prolonged bacterial culture to identify late periprosthetic joint infection: a promising strategy. Clin Infect Dis. 2008 Dec 1;47(11):1403-9. 45. Gollwitzer H, Diehl P, Gerdesmeyer L, Mittelmeier W. [Diagnostic strategies in cases of suspected periprosthetic infection of the knee. A review of the literature and current recommendations]. Orthopade. 2006 Sep;35(9):904-16: 906-8: 910-6. 46. Ince A, Rupp J, Frommelt L, Katzer A, Gille J, L¨ohr JF. Is ‘‘aseptic’’ loosening of the prosthetic cup after total hip replacement due to nonculturable bacterial pathogens in patients with low-grade infection? Clin Infect Dis. 2004 Dec 1;39(11):1599603. Epub 2004 Nov 02. 47. Pitt WG, Ross SA. Ultrasound increases the rate of bacterial cell growth. Biotechnol Prog. 2003 May-Jun;19(3):1038-44. 48. Anguita-Alonso P, Hanssen AD, Patel R. Prosthetic joint infection. Expert Rev Anti Infect Ther. 2005 Oct;3(5):797-804. 49. Dora C, Altwegg M, Gerber C, B¨ottger EC, Zbinden R. Evaluation of conventional microbiological procedures and molecular genetic techniques for diagnosis of infections in patients with implanted orthopedic devices. J Clin Microbiol. 2008 Feb;46(2):824-5. Epub 2007 Nov 26. 50. Esteban J, Gomez-Barrena E, Cordero J, Martı´n-de-Hijas NZ, Kinnari TJ, Fernandez-Roblas R. Evaluation of quantitative analysis of cultures from sonicated

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retrieved orthopedic implants in diagnosis of orthopedic infection. J Clin Microbiol. 2008 Feb;46(2):488-92. Epub 2007 Dec 12. 51. Piper KE, Jacobson MJ, Cofield RH, Sperling JW, Sanchez-Sotelo J, Osmon DR, McDowell A, Patrick S, Steckelberg JM, Mandrekar JN, Fernandez Sampedro M, Patel R. Microbiologic diagnosis of prosthetic shoulder infection by use of implant sonication. J Clin Microbiol. 2009 Jun;47(6):1878-84. Epub 2009 Mar 04. 52. Achermann Y, Vogt M, Leunig M, W¨ust J, Trampuz A. Improved diagnosis of periprosthetic joint infection by multiplex PCR of sonication fluid from removed implants. J Clin Microbiol. 2010 Apr;48(4):1208-14. Epub 2010 Feb 17. 53. Aggarwal VK, Tischler E, Ghanem E, Parvizi J. Leukocyte esterase from synovial fluid aspirate: a technical note. J Arthroplasty. 2013 Jan;28(1):193-5. Epub 2012 Aug 03. 54. Wetters NG, Berend KR, Lombardi AV, Morris MJ, Tucker TL, Della Valle CJ. Leukocyte esterase reagent strips for the rapid diagnosis of periprosthetic joint infection. J Arthroplasty. 2012 Sep;27(8)(Suppl):8-11. Epub 2012 May 17. 55. Parvizi J, Adeli B, Zmistowski B, Restrepo C, Greenwald AS. Management of periprosthetic joint infection: the current knowledge: AAOS exhibit selection. J Bone Joint Surg Am. 2012 Jul 18;94(14):e104. 56. Parvizi J, McKenzie JC, Cashman JP. Diagnosis of periprosthetic joint infection using synovial C-reactive protein. J Arthroplasty. 2012 Sep;27(8)(Suppl):12-6. Epub 2012 May 04. 57. Bartlett JM, Stirling D. A short history of the polymerase chain reaction. Methods Mol Biol. 2003;226:3-6. 58. Mariani BD, Martin DS, Levine MJ, Booth RE Jr, Tuan RS. The Coventry Award. Polymerase chain reaction detection of bacterial infection in total knee arthroplasty. Clin Orthop Relat Res. 1996 Oct;(331):11-22. 59. Tunney MM, Patrick S, Curran MD, Ramage G, Hanna D, Nixon JR, Gorman SP, Davis RI, Anderson N. Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene. J Clin Microbiol. 1999 Oct;37(10):3281-90. 60. Dempsey KE, Riggio MP, Lennon A, Hannah VE, Ramage G, Allan D, Bagg J. Identification of bacteria on the surface of clinically infected and non-infected prosthetic hip joints removed during revision arthroplasties by 16S rRNA gene sequencing and by microbiological culture. Arthritis Res Ther. 2007;9(3):R46. 61. Fihman V, Hannouche D, Bousson V, Bardin T, Liot´e F, Raskine L, Riahi J, Sanson-Le Pors MJ, Bercxot B. Improved diagnosis specificity in bone and joint infections using molecular techniques. J Infect. 2007 Dec;55(6):510-7. Epub 2007 Oct 29. 62. Moojen DJ, Spijkers SN, Schot CS, Nijhof MW, Vogely HC, Fleer A, Verbout AJ, Castelein RM, Dhert WJ, Schouls LM. Identification of orthopaedic infections using broad-range polymerase chain reaction and reverse line blot hybridization. J Bone Joint Surg Am. 2007 Jun;89(6):1298-305.

63. Gallo J, Kolar M, Dendis M, Loveckova Y, Sauer P, Zapletalova J, Koukalova D. Culture and PCR analysis of joint fluid in the diagnosis of prosthetic joint infection. New Microbiol. 2008 Jan;31(1):97-104. 64. Kobayashi N, Procop GW, Krebs V, Kobayashi H, Bauer TW. Molecular identification of bacteria from aseptically loose implants. Clin Orthop Relat Res. 2008 Jul;466(7):1716-25. Epub 2008 Apr 26. 65. Riggio MP, Dempsey KE, Lennon A, Allan D, Ramage G, Bagg J. Molecular detection of transcriptionally active bacteria from failed prosthetic hip joints removed during revision arthroplasty. Eur J Clin Microbiol Infect Dis. 2010 Jul;29(7):823-34. Epub 2010 May 08. 66. Marı´n M, Garcia-Lechuz JM, Alonso P, Villanueva M, Alcal´a L, Gimeno M, Cercenado E, S´anchez-Somolinos M, Radice C, Bouza E. Role of universal 16S rRNA gene PCR and sequencing in diagnosis of prosthetic joint infection. J Clin Microbiol. 2012 Mar;50(3):583-9. Epub 2011 Dec 14. 67. Borst A, Box AT, Fluit AC. False-positive results and contamination in nucleic acid amplification assays: suggestions for a prevent and destroy strategy. Eur J Clin Microbiol Infect Dis. 2004 Apr;23(4):289-99. Epub 2004 Mar 10. 68. Panousis K, Grigoris P, Butcher I, Rana B, Reilly JH, Hamblen DL. Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92 cases. Acta Orthop. 2005 Jun;76(3):341-6. 69. Bergin PF, Doppelt JD, Hamilton WG, Mirick GE, Jones AE, Sritulanondha S, Helm JM, Tuan RS. Detection of periprosthetic infections with use of ribosomal RNA-based polymerase chain reaction. J Bone Joint Surg Am. 2010 Mar;92(3): 654-63. 70. Birmingham P, Helm JM, Manner PA, Tuan RS. Simulated joint infection assessment by rapid detection of live bacteria with real-time reverse transcription polymerase chain reaction. J Bone Joint Surg Am. 2008 Mar;90(3):602-8. 71. Tarkin IS, Henry TJ, Fey PI, Iwen PC, Hinrichs SH, Garvin KL. PCR rapidly detects methicillin-resistant staphylococci periprosthetic infection. Clin Orthop Relat Res. 2003 Sep;(414):89-94. 72. Kobayashi N, Inaba Y, Choe H, Iwamoto N, Ishida T, Yukizawa Y, Aoki C, Ike H, Saito T. Rapid and sensitive detection of methicillin-resistant Staphylococcus periprosthetic infections using real-time polymerase chain reaction. Diagn Microbiol Infect Dis. 2009 Jun;64(2):172-6. Epub 2009 Apr 02. 73. Jacovides CL, Kreft R, Adeli B, Hozack B, Ehrlich GD, Parvizi J. Successful identification of pathogens by polymerase chain reaction (PCR)-based electron spray ionization time-of-flight mass spectrometry (ESI-TOF-MS) in culture-negative periprosthetic joint infection. J Bone Joint Surg Am. 2012 Dec 19;94(24):2247-54. 74. Jacob D, Sauer U, Housley R, Washington C, Sannes-Lowery K, Ecker DJ, Sampath R, Grunow R. Rapid and high-throughput detection of highly pathogenic bacteria by Ibis PLEX-ID technology. PLoS One. 2012;7(6):e39928. Epub 2012 Jun 29.

Culture-negative periprosthetic joint infection.

➤ Negative results on culture still pose a real challenge in the diagnosis of periprosthetic joint infection.➤ There are numerous reasons for the inab...
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