Prosthetic Joint Infection Diagnosis Using Conventional Methods
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11/5/2018 Prosthetic Joint Infection Diagnosis Using Conventional Methods HOT TOPIC / 2018 ©MFMER 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 ©MFMER 1 11/5/2018 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 ©MFMER Total Hip and Knee Replacement Procedures United States1 Total knee Total hip Year ©MFMER 2 11/5/2018 ©MFMER Prosthetic Hip and Knee Infections: United States2 2001‐2020 ©MFMER 3 11/5/2018 Surgical Management of Prosthetic Hip or Knee Infection3 Reprinted with permission from Massachusetts Medical Society. ©MFMER Prosthetic Joint Infection Microbiology4 Hip and Knee Hip Knee Shoulder Elbow All time periods Early Number of joints 2435 637 1979 1427 199 110 Staphylococcus aureus 27 38 13 23 18 42 Coagulase negative staphylococci 27 22 30 23 41 41 Streptococcus species 846644 Enterococcus species 310223 0 Aerobic gram negative bacilli 92475107 Anaerobic bacteria 4395 Cutibacterium acnes 24 1 Other anaerobes 30 Culture negative 14 10 7 11 15 5 Polymicrobial 15 31 14 12 16 3 Other 3 ©MFMER 4 11/5/2018 Unusual Causes of Prosthetic Joint Infection5 Actinomyces israelii Granulicatella adiacens Aspergillus fumigatus Haemophilus parainfluenzae Arcanobacterium bernardie Histoplasma capsulatum Bacteroides species Listeria monocytogenes Brucella species Moraxella catarrhalis Campylobacter species Mycobacterium abscessus, avium complex, chelonae, farcinogenes, Candida species fortuitum, kansasii, smegmatis, tuberculosis complex, wolinskyi Capnocytophaga canimorsus Mycoplasma hominis, Mycoplasma salivarium Chlamydophila pneumoniae Oerskovia xanthineolytica Chryseobacterium meningosepticum Pasteurella multocida Clostridium species Rhodotorula mucilaginosa, minuta Corynebacterium species Rothia species Cryptococcus neoformans Sporothrix schenkii Echinococcus species Tropheryma whipplei Erysipelothrix rhusiopathiae Veillonella species Francisella tularensis ©MFMER ©MFMER 5 11/5/2018 Prosthetic Joint Infection Clinical Presentation No. (%) Author Pain Swelling Fever Drainage Windsor et al. JBJS (Am) 1990;72:272 26 (100) 20 (77) 7 (27) 7 (27) Morrey et al. CORR 1989;248:120 69 (95) 69 (95) ----- 26 (36) McDonald et al. JBJS (Am) 1989;71:828 78 (95) ------ 3 (4) 19 (23) Total 173/181 (96) 89/99 (90) 10/108 (9) 52/181 (29) Courtesy of Douglas R. Osmon, MD ©MFMER Criteria for Diagnosis of Prosthetic Joint Infection6-8 Definitions of Prosthetic Joint Infection 2011 2013 2013 Musculoskeletal Infection Infectious Diseases Society International Consensus8 Society6 of America7 Definitive Supportive Definitive Supportive Definitive Supportive evidence evidence evidence evidence evidence evidence Sinus tract communicating with the prosthesis xxx Identical microorganism isolated from ≥2 cultures xxx Purulence surrounding the prosthesis xx Acute inflammation of periprosthetic tissue xx x A single culture with any microorganism xx A single culture with a virulent microorganism x Elevated synovial fluid leukocyte count xx Elevated synovial fluid neutrophil percentage xx Elevated serum ESR and CRP xx ©MFMER 6 11/5/2018 C-Reactive Protein Erythrocyte Sedimentation Rate9 Knee Implants Aseptic Failure Prosthetic Joint Infection P-Value (n=297) (n=215) (n=82) ESR, mm/h 11 (0-68) 53.5 (6-128) <0.0001 CRP, mg/L 4 (0.1-174) 51 (3-444) <0.0001 Hip Implants Aseptic Failure Prosthetic Joint Infection (n=221) (n=187) (n=34) ESR, mm/h 11 (0-94) 30 (3-137) <0.0001 CRP, mg/L 3 (0.3-141) 18 (3-288) <0.0001 Shoulder Implants Aseptic Failure Prosthetic Joint Infection (n=64) (n=45) (n=19) ESR, mm/h 10 (0-32) 9 (1-71) 0.9883 CRP, mg/L 3 (3-26) 10 (3-40) 0.01 ©MFMER C-Reactive Protein Erythrocyte Sedimentation Rate9 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 ©MFMER 7 11/5/2018 Anterior bone Anterior 111In-labeled leukocyte 99m ( Tc methylene diphosphonate) image showing accumulation of scan image showing increased labeled leukocytes spatially activity around the femoral congruent with the bone image. component of a left hip replacement. © Weisheng Ye, Wei Shang and Yaqiong Yang (2012). Licensee InTechOpen.10 (open access) ©MFMER 18F-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) ©MFMER 8 11/5/2018 Synovial Fluid Leukocyte/Differential Prosthetic Knee11 * * * Leukocytes >1.7 94% 88% Neutrophils >65% 97% 98% * ©MFMER 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 5 33 100 100 100 Athanasou et al. JBJS(Br) 1995;77:28 JC, IM Hip/knee 1 106 90 96 88 Lonner et al. JBJS(Am) 1996;78:1553 JC, IM, ASPI Hip/knee 5 175 84 96 70 10 84 99 89 Pace et al. J Arthroplasty 1997;12:64 JC, IM Hip/knee 5 18 82 93 82 Abdul‐Karim et al. Mod Pathol 1998;11:427 IM, ST, UDT Hip/knee 5 64 43 97 60 Banit et al. CORR 2002;401:230 JC, ASPI Knee 10 55 100 96 82 Hip 10 63 45 92 55 Musso et al. Postgrad Med J 2003;79:590 JC, IM, ASPI Hip/knee 5 45 50 95 60 Wong et al. J Arthroplasty 2005;20:1015 JC, IM, SS Hip/knee 5 33 93 77 68 10 86 85 75 Ko et al. J Arthroplasty 2005;20:189 JC, IM, ASPI Hip/knee 5 40 67 97 86 Frances Borrego et al. Int Orthop 2007;31:33 PST Hip 10 63 67 90 80 Knee 83 50 100 100 Nunez et al. Acta Orthop 2007;78:226 JC, IM, ASPI Hip 5 136 86 87 79 Tohtz et al. CORR 2010;468:762 IM Hip 10 52 87 100 100 *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 11/5/2018 Prospective Vortexing/Sonication Clinical Study Hip or Knee Implants12 ©MFMER Staphylococcus epidermidis Biofilm on Polycarbonate Coupons Scanning Electron Microscopy Soaking Scraping Sonication Magnification x 4.00k, WD=14.4 mm ©MFMER 10 11/5/2018 Tissue Sonicate ©MFMER Prospective Vortexing/Sonication Clinical Study Hip or Knee Implants12 • 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 ©MFMER 11 11/5/2018 Definition of Prosthetic Hip and Knee Infection • At least 1 of the following criteria6: • Visible purulence of synovial fluid or intraoperatively • Acute inflammation on histopathologic tissue examination • Presence of a sinus tract communicating with the prosthesis ©MFMER Number of Microorganisms Detected by Sonicate Fluid Culture12 Reprinted with permission from Massachusetts Medical Society. ©MFMER 12 11/5/2018 Results Prosthetic Hip or Knee Infection Aseptic failure Prosthetic joint infection (n=252) (n=79) Synovial fluid 1.9% 56.3% Periprosthetic tissue 0.8% 60.8% P <0.001 Sonicate fluid 1.2% 78.5% ©MFMER Prospective Clinical Study Shoulder Implants • Patients undergoing total shoulder implant revision or resection for aseptic failure or presumed infection7 • Mayo Clinic: August 2004–November 2008 • Exclusion criteria: • <2 tissues were cultured • Partial revision • Sonicate fluid not archived ©MFMER 13 11/5/2018 Definition of Definite Prosthetic Shoulder Infection • At least 1 of the following criteria7: • Visible purulence of synovial fluid or intraoperatively • Acute inflammation on histopathologic tissue examination • Presence of a sinus tract communicating with the prosthesis ©MFMER Prospective Clinical Study Shoulder Implants Definite prosthetic Aseptic failure (n=101) shoulder infection (n=33) Periprosthetic tissue 96 (95.1%) 18 (54.5%) P=0.046 Sonicate fluid 99 (98.0%) 22 (66.7%) ©MFMER 14 11/5/2018 Acknowledgments • Kerryl Greenwood-Quaintance, MS • Rizwan Sohail, MD • Melissa Karau • Harmony Tyner, MD • Suzannah Schmidt, MS • Paschalis Vergidis, MD • Matt Thoendel, MD, PhD • James Steckelberg, MD • Morgan Ivy • Elie Berbari, MD • Aaron Tande, MD • Franklin Cockerill, MD • Patricio Jeraldo, PhD • Jayawant Mandrekar, PhD • Nicholas Chia, PhD • Arlen Hanssen, MD • Trisha Peel, MD • Matt Abdek, MD • Douglas Osmon, MD • David Lewallen, MD • Thao Masters, PhD • Robert Trousdale, MD • Charles Cazanave, MD • Mark Pagnano, MD • Marta Fernandez-Sampedro, MD • Miguel Cabanela, MD • Trisha Peel, PhD • David Jacofsky, MD • Yu Mi Wi, MD • Franklin Sim, MD • Andrej Trampuz, MD • Daniel Berry, MD • Paolo Melendez, MD • Michael Stuart, MD • Eric Gomez-Urena, MD • Robert Cofield, MD • Cassandra Brinkman, PhD • Paul Huddleston, MD • Mark Rouse • John Sperling, MD • Jon Badiola, MD • Joaquin Sanchez-Sotelo, MD • Qun Yan, MD • Mark Dekutoski, MD • Kimberly Perez • Bradford Currier, MD • Morgan Ivy • Mike Yaszemski, MD • Paloma Anguita Alonso, MD • Youlonda Loechler • Maria Ruiz Ruizgomez, MD • Krishnan Unni, MD • Awele Maduka-Ezeh, MD • James Greenleaf, PhD • Jin Won Chung, MD • James Uhl • Jose del Pozo, MD • Scott Cunningham, MS • Seong Yeol Ryu, MD • Clinical Microbiology Bacteriology and IP Staff • Larry Baddour, MD • Mayo Clinic patients ©MFMER References 1.