Prosthetic Joint Infection.Updated2 · Hip and Knee Hip Knee Shoulder Elbow All time periods Early ... Definition of Definite Prosthetic Shoulder Infection • At least 1 of the following

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Prosthetic Joint Infection Diagnosis Using Conventional Methods

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Presenter:

Robin Patel, M.D.Professor of Medicine and MicrobiologyChair, 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 8 4 6 6 4 4

Enterococcus species 3 10 2 2 3 0

Aerobic gram negative bacilli 9 24 7 5 10 7

Anaerobic bacteria 4 3 9 5

Cutibacterium acnes 24 1

Other anaerobes 3 0

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

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

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Prosthetic Joint Infection Clinical Presentation

Courtesy of Douglas R. Osmon, MD

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)

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Criteria for Diagnosis of Prosthetic Joint Infection6-8

Definitions of Prosthetic Joint Infection2011

Musculoskeletal Infection 

Society6

2013

Infectious Diseases Society 

of America7

2013

International Consensus8

Definitive 

evidence

Supportive 

evidence

Definitive 

evidence

Supportive 

evidence

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

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C-Reactive Protein Erythrocyte Sedimentation Rate9

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) <0.0001

CRP, mg/L 4 (0.1-174) 51 (3-444) <0.0001

Hip Implants (n=221)

Aseptic Failure (n=187)

Prosthetic Joint Infection (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 (n=64)

Aseptic Failure (n=45)

Prosthetic Joint Infection (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

PPV=positive predictive value

NPV=negative predictive value

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)

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Anterior 111In-labeled leukocyte image showing accumulation of labeled leukocytes spatially congruent with the bone image.

Anterior bone (99mTc methylene diphosphonate) scan image showing increased activity around the femoral component of a left hip replacement.

© Weisheng Ye, Wei Shang and Yaqiong Yang (2012). Licensee InTechOpen.10 (open access)

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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)

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Synovial Fluid Leukocyte/Differential Prosthetic Knee11

*

*

**

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 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 valueJC, 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 StudyHip or Knee Implants12

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Staphylococcus epidermidis Biofilm on Polycarbonate Coupons Scanning Electron Microscopy

Soaking Scraping SonicationMagnification x 4.00k, WD=14.4 mm

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SonicateTissue

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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 InfectionAseptic 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

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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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P=0.046

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%)

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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

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References1. 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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References7. 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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