Prosthetic Joint Infection Diagnosis Using Conventional Methods

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1 Prosthetic Joint Infection Diagnosis Using Conventional Methods HOT TOPIC / 2018 Presenter: Robin Patel, M.D. Professor of Medicine and Microbiology Chair, Division of Clinical Microbiology and the Elizabeth P. and Robert E. Allen Professor of Individualized Medicine Department of Laboratory Medicine and Pathology at Mayo Clinic, Rochester, Minnesota 1

2 Disclosures Dr. Robin Patel has a US patent for a method and an apparatus for sonication, but has foregone her right to personally receive royalties. Funding National Institutes of Health Department of Defense National Science Foundation Total Hip and Knee Replacement Procedures United States 1 Total knee Total hip Year 2

3 Prosthetic Hip and Knee Infections: United States

4 Surgical Management of Prosthetic Hip or Knee Infection 3 Reprinted with permission from Massachusetts Medical Society. Prosthetic Joint Infection Microbiology 4 Hip and Knee Hip Knee Shoulder Elbow All time periods Early Number of joints Staphylococcus aureus Coagulase negative staphylococci Streptococcus species Enterococcus species Aerobic gram negative bacilli Anaerobic bacteria Cutibacterium acnes 24 1 Other anaerobes 3 0 Culture negative Polymicrobial Other 3 4

5 Unusual Causes of Prosthetic Joint Infection 5 Actinomyces israelii Aspergillus fumigatus Arcanobacterium bernardie Bacteroides species Brucella species Campylobacter species Candida species Capnocytophaga canimorsus Chlamydophila pneumoniae Chryseobacterium meningosepticum Clostridium species Corynebacterium species Cryptococcus neoformans Echinococcus species Erysipelothrix rhusiopathiae Francisella tularensis Granulicatella adiacens Haemophilus parainfluenzae Histoplasma capsulatum Listeria monocytogenes Moraxella catarrhalis Mycobacterium abscessus, avium complex, chelonae, farcinogenes, fortuitum, kansasii, smegmatis, tuberculosis complex, wolinskyi Mycoplasma hominis, Mycoplasma salivarium Oerskovia xanthineolytica Pasteurella multocida Rhodotorula mucilaginosa, minuta Rothia species Sporothrix schenkii Tropheryma whipplei Veillonella species 5

6 Prosthetic Joint Infection Clinical Presentation No. (%) Author Pain Swelling Fever Drainage Windsor et al. JBJS (Am) 1990;72: (100) 20 (77) 7 (27) 7 (27) Morrey et al. CORR 1989;248: (95) 69 (95) (36) McDonald et al. JBJS (Am) 1989;71: (95) (4) 19 (23) Total 173/181 (96) 89/99 (90) 10/108 (9) 52/181 (29) Courtesy of Douglas R. Osmon, MD Criteria for Diagnosis of Prosthetic Joint Infection Musculoskeletal Infection Society 6 Definitive evidence Definitions of Prosthetic Joint Infection Supportive evidence 2013 Infectious Diseases Society of America 7 Definitive evidence Supportive evidence 2013 International Consensus 8 Definitive evidence Supportive evidence Sinus tract communicating with the prosthesis x x x Identical microorganism isolated from 2 cultures x x x Purulence surrounding the prosthesis x x Acute inflammation of periprosthetic tissue x x x A single culture with any microorganism x x A single culture with a virulent microorganism x Elevated synovial fluid leukocyte count x x Elevated synovial fluid neutrophil percentage x x Elevated serum ESR and CRP x x 6

7 C-Reactive Protein Erythrocyte Sedimentation Rate 9 Knee Implants (n=297) Aseptic Failure (n=215) Prosthetic Joint Infection (n=82) P-Value ESR, mm/h 11 (0-68) 53.5 (6-128) < CRP, mg/l 4 ( ) 51 (3-444) < Hip Implants (n=221) Aseptic Failure (n=187) Prosthetic Joint Infection (n=34) ESR, mm/h 11 (0-94) 30 (3-137) < CRP, mg/l 3 ( ) 18 (3-288) < Shoulder Implants (n=64) Aseptic Failure (n=45) Prosthetic Joint Infection (n=19) ESR, mm/h 10 (0-32) 9 (1-71) CRP, mg/l 3 (3-26) 10 (3-40) 0.01 C-Reactive Protein Erythrocyte Sedimentation Rate 9 Sensitivity Specificity PPV NPV Knee Implants ESR >30 mm/h 71 (58/82) 89 (191/215) 71 (58/82) 89 (191/215) CRP >10 mg/l 83 (68/82) 79 (170/215) 60 (68/113) 92 (170/184) Hip Implants ESR >30 mm/h 47 (16/34) 84 (158/187) 36 (16/45) 90 (158/176) CRP >10 mg/l 74 (25/34) 78 (146/187) 38 (25/66) 94 (146/155) Shoulder Implants ESR >30 mm/h 16 (3/19) 98 (44/45) 75 (3/4) 73 (44/60) CRP >10 mg/l 42 (8/19) 84 (38/45) 53 (8/15) 78 (38/49) PPV=positive predictive value NPV=negative predictive value 7

8 Anterior bone ( 99m Tc methylene diphosphonate) scan image showing increased activity around the femoral component of a left hip replacement. Anterior 111 In-labeled leukocyte image showing accumulation of labeled leukocytes spatially congruent with the bone image. Weisheng Ye, Wei Shang and Yaqiong Yang (2012). Licensee InTechOpen. 10 (open access) 18 F-fluoro-2-deoxyglucose Positron Emission Tomography/Computed Tomography Increased Activity Around the Bone-Prosthesis Interface Weisheng Ye, Wei Shang and Yaqiong Yang (2012). Licensee InTechOpen.10 (open access) 8

9 Synovial Fluid Leukocyte/Differential Prosthetic Knee 11 * * * Leukocytes >1.7 94% 88% Neutrophils >65% 97% 98% * Studies of Intrasurgical Frozen-Section Histopathologic Findings of Acute Inflammation in Prosthetic Joint Infection Diagnosis Reference Specimen Joint #PMN* n Sensitivity Specificity PPV** Feldman et al. JBJS(Am) 1995;77:1807 JC, IM Hip/knee Athanasou et al. JBJS(Br) 1995;77:28 JC, IM Hip/knee Lonner et al. JBJS(Am) 1996;78:1553 JC, IM, ASPI Hip/knee Pace et al. J Arthroplasty 1997;12:64 JC, IM Hip/knee Abdul Karim et al. Mod Pathol 1998;11:427 IM, ST, UDT Hip/knee Banit et al. CORR 2002;401:230 JC, ASPI Knee Hip Musso et al. Postgrad Med J 2003;79:590 JC, IM, ASPI Hip/knee Wong et al. J Arthroplasty 2005;20:1015 JC, IM, SS Hip/knee Ko et al. J Arthroplasty 2005;20:189 JC, IM, ASPI Hip/knee Frances Borrego et al. Int Orthop 2007;31:33 PST Hip Knee Nunez et al. Acta Orthop 2007;78:226 JC, IM, ASPI Hip Tohtz et al. CORR 2010;468:762 IM Hip *Some studies used >, others the number shown, **Positive predictive value JC, joint pseudocapsule; IM, interface membrane; ASPI, any area that appears suspicious for possible infection; ST, synovial tissue; SS, synovial surface; UDT, unusually discolored tissue; PST, periprosthetic soft tissue 9

10 Prospective Vortexing/Sonication Clinical Study Hip or Knee Implants 12 Staphylococcus epidermidis Biofilm on Polycarbonate Coupons Scanning Electron Microscopy Soaking Scraping Sonication Magnification x 4.00k, WD=14.4 mm 10

11 Tissue Sonicate Prospective Vortexing/Sonication Clinical Study Hip or Knee Implants 12 Patients undergoing total knee or hip revision or resection for aseptic failure or presumed infection Mayo Clinic: August 2003 December 2005 Exclusion criteria: Components contaminated in OR Components did not fit in container <2 tissues were cultured Partial revision 11

12 Definition of Prosthetic Hip and Knee Infection At least 1 of the following criteria 6 : Visible purulence of synovial fluid or intraoperatively Acute inflammation on histopathologic tissue examination Presence of a sinus tract communicating with the prosthesis Number of Microorganisms Detected by Sonicate Fluid Culture 12 Reprinted with permission from Massachusetts Medical Society. 12

13 Results Prosthetic Hip or Knee Infection Aseptic failure (n=252) Prosthetic joint infection (n=79) Synovial fluid 1.9% 56.3% Periprosthetic tissue 0.8% 60.8% Sonicate fluid 1.2% 78.5% P <0.001 Prospective Clinical Study Shoulder Implants Patients undergoing total shoulder implant revision or resection for aseptic failure or presumed infection 7 Mayo Clinic: August 2004 November 2008 Exclusion criteria: <2 tissues were cultured Partial revision Sonicate fluid not archived 13

14 Definition of Definite Prosthetic Shoulder Infection At least 1 of the following criteria 7 : Visible purulence of synovial fluid or intraoperatively Acute inflammation on histopathologic tissue examination Presence of a sinus tract communicating with the prosthesis Prospective Clinical Study Shoulder Implants Aseptic failure (n=101) Definite prosthetic shoulder infection (n=33) Periprosthetic tissue 96 (95.1%) 18 (54.5%) Sonicate fluid 99 (98.0%) 22 (66.7%) P=

15 Acknowledgments Kerryl Greenwood-Quaintance, MS Melissa Karau Suzannah Schmidt, MS Matt Thoendel, MD, PhD Morgan Ivy Aaron Tande, MD Patricio Jeraldo, PhD Nicholas Chia, PhD Trisha Peel, MD Douglas Osmon, MD Thao Masters, PhD Charles Cazanave, MD Marta Fernandez-Sampedro, MD Trisha Peel, PhD Yu Mi Wi, MD Andrej Trampuz, MD Paolo Melendez, MD Eric Gomez-Urena, MD Cassandra Brinkman, PhD Mark Rouse Jon Badiola, MD Qun Yan, MD Kimberly Perez Morgan Ivy Paloma Anguita Alonso, MD Maria Ruiz Ruizgomez, MD Awele Maduka-Ezeh, MD Jin Won Chung, MD Jose del Pozo, MD Seong Yeol Ryu, MD Larry Baddour, MD Rizwan Sohail, MD Harmony Tyner, MD Paschalis Vergidis, MD James Steckelberg, MD Elie Berbari, MD Franklin Cockerill, MD Jayawant Mandrekar, PhD Arlen Hanssen, MD Matt Abdek, MD David Lewallen, MD Robert Trousdale, MD Mark Pagnano, MD Miguel Cabanela, MD David Jacofsky, MD Franklin Sim, MD Daniel Berry, MD Michael Stuart, MD Robert Cofield, MD Paul Huddleston, MD John Sperling, MD Joaquin Sanchez-Sotelo, MD Mark Dekutoski, MD Bradford Currier, MD Mike Yaszemski, MD Youlonda Loechler Krishnan Unni, MD James Greenleaf, PhD James Uhl Scott Cunningham, MS Clinical Microbiology Bacteriology and IP Staff Mayo Clinic patients References 1. Kurtz S, Ong K, Lau E, et al: Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to J Bone Joint Surg Am. Apr 2007;89: Kurtz S, Lau E, Watson H, et al: Economic burden of periprosthetic joint infection in the United States. J Arthroplasty. Sept 2002;8: Del Pozo J, Patel Robin: Infection associated with prosthetic joints. N Engl J Med. Aug 2009;361: Tande A, Patel R: Prosthetic joint infection. Clin Microbiol Rev. Apr 2014;27(2): Marculescu C, Berbari EF, Cockerill III FR, et al: Unusual aerobic and anaerobic bacteria associated with prosthetic join infections. Clin Orthop Relat Res 2006;451: Parvizi J, Zmistowski B, Berbari EF, et al: New definition of periprosthetic joint infection: from the workgroup of the Musculoskeletal Infection Society. Clin Orthop Relat Res. Nov 2011;469(11):

16 References 7. Osmon D, Berbari EF, Berendt AR, et al: Diagnosis and management of prosthetic joint infection: clinical practice guidelines by the Infectious Diseases Society of America. Clinical Infectious Diseases. Jan 2013;56(1):e1-e Parvizi J, Gehrke T, Chen AF: Proceedings of the international consensus on periprosthetic joint injection. Bone Joint J. 2013;95-B: Piper K, Fernandez-Sampedro M, Steckelberg K, et al: C-reactive protein, erythrocyte sedimentation rate and orthopedic implant infection. PLoS One. Feb 2010;5(2):e Ye W, Shang W, Yang Y: Staphylococcus infection associated with arthroplasty, recent advances in artoplasty, Dr. Samo Fokter (Ed.), ISBN: , InTech, Available from: Trampuz A, Hanssen AD, Osmon D, et al: Synovial fluid leukocyte count and differential for the diagnosis of prosthetic knee infection. Am J Med. Oct 2004;117(8): Trampuz A, Piper K, Jacobson M, et al: Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med. Aug 2007;357: Questions or requests to: MMLEducation@mayo.edu For more information Visit MayoMedicalLaboratories.com or call Mayo Laboratory Inquiry at HOT TOPIC /

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