Prosthetic Joint Infection Diagnosis Using Conventional Methods

11/5/2018

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

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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

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Total Hip and Knee Replacement Procedures United States1 Total knee

Total hip

Year

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Prosthetic Hip and Knee Infections: United States2

2001‐2020

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Surgical Management of Prosthetic Hip or Knee Infection3

Reprinted with permission from Massachusetts Medical Society.

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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

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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

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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

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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

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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

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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

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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.

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18F-fluoro-2-deoxyglucose Positron Emission Tomography/Computed Tomography Increased Activity Around the Bone-Prosthesis Interface

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Synovial Fluid Leukocyte/Differential Prosthetic Knee11

* * *

Leukocytes >1.7 94% 88% Neutrophils >65% 97% 98%

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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

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Prospective Vortexing/Sonication Clinical Study Hip or Knee Implants12

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Staphylococcus epidermidis Biofilm on Polycarbonate Coupons Scanning Electron Microscopy

Soaking Scraping Sonication Magnification x 4.00k, WD=14.4 mm

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Tissue Sonicate

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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

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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

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Number of Microorganisms Detected by Sonicate Fluid Culture12

Reprinted with permission from Massachusetts Medical Society.

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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%

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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

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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

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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%)

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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

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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 2030. J Bone Joint Surg Am. Apr 2007;89:780–5. 2. Kurtz S, Lau E, Watson H, et al: Economic burden of periprosthetic joint infection in the United States. J Arthroplasty. Sept 2002;8:61-653. 3. Del Pozo J, Patel Robin: Infection associated with prosthetic joints. N Engl J Med. Aug 2009;361:787-794. 4. Tande A, Patel R: Prosthetic joint infection. Clin Microbiol Rev. Apr 2014;27(2):302-345. 5. Marculescu C, Berbari EF, Cockerill III FR, et al: Unusual aerobic and anaerobic bacteria associated with prosthetic join infections. Clin Orthop Relat Res 2006;451:55-72. 6. 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):2992-2994.

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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-e25. 8. Parvizi J, Gehrke T, Chen AF: Proceedings of the international consensus on periprosthetic joint injection. Bone Joint J. 2013;95-B:1450-1452. 9. 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):e9358. 10. Ye W, Shang W, Yang Y: Staphylococcus infection associated with arthroplasty, recent advances in artoplasty, Dr. Samo Fokter (Ed.), ISBN: 978-953-307-990-5, InTech, Available from: http://www.intechopen.com/books/recent-advances-in-arthroplasty/staphylococcus-infection-associated- with-arthroplasty. 11. 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):556-562. 12. 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;357:654-663.

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