Diagnosis of PJI. Andrej Trampuz Charité Universitätsmedizin Berlin Germany

Transcription

1 Diagnosis of PJI Andrej Trampuz Charité Universitätsmedizin Berlin Germany

2 MOP, MOM, COC bearing couples Acute or fatigue implant fracture, oxidative degredation, corrosion Production errors, improper materials or design Aggresive activity - sports Wear particles Infection Artifical joint material failure Acute mechanical overload Chronic mechanical overload Periprosthetic fracture Bone to implant interface failure Metal ion release Excessive micromotion Bone to implant toughness mismatch Osteolysis Hypersensitivity, mutagenicity? ARTIFICIAL JOINT FAILURE: loosening, dislocation, neurovascular deficits, tendon lesions, limb lenght discrepancy, poor range of motion, pain, sounds Excessive rigidity Sistemic alterations Stress shielding, week bone Unnatural force transfer Implant positioning, poor approach complication rate Preoperative diagnosis Effective joint space fluid pressure Poor surgical technique poor education, low surgical volume

3 Key to success in PJI Diagnosis Antibiotics Directed against biofilms Surgery Cure rate > 90%

4 Is it an infection? Deny the problem Ostriches Humans bury their heads in the sand to avoid danger avoid an apparently risky situation by pretending it doesn t exist

5 Diagnostic approach Is it an infection? Is it acute or chronic? Which pathogen?

6 Biology meets mechanics Antibiotics Antimicrobial resistance Microorganism (biofilm formation, susceptibility) Virulence Defense Host (inflammatory response) Implant

7 Many faces of infection

8 Definition criteria MSIS/ICM IDSA EBJIS Proposed EBJIS Definitive evidence x x x x x x x Supportive evidence x x Tande AJ at al. CMR 2014 Renz N et al. JBJS 2018

9 Proposed EBJIS definition (2018) Diagnosis of periprosthetic joint infection is confirmed if at least 1 criteria is fulfilled: Test Criteria Sensitivity Specificity Clinical features Leukocytes in synovial fluid Sinus tract (fistula) or visible purulence around the prosthesis >2000/µl leukocytes or 70% granulocytes 20-30% 100% 90% 95% Histology Inflammation in periprosthetic tissue (>5 73% 95% Microbiology granulocytes/hpf) Microbial growth in: Synovial fluid 2 periprosthetic tissue samples* Sonication fluid ( 50 CFU/ml) 45-75% 60-80% 80-90% 95% 92% 95% *For highly virulent organisms (e.g. S. aureus, E. coli) 1 positive tissue sample is sufficient.

10 It is all about definition... Characteristic All patients (n=212) Median patient age (range) 70 years (41-94) Female gender, no (%) 106 (50) Joint Knee 151 (71) Hip 61 (29) Classification, no. (%) Early (<3 months) 33 (16) Delayed (3-24 months) 79 (37) Late (>24 months) 100 (47) Musculoskeletal swiss Proposed orthopaedics European and Infection Society Bone Swiss and Society Joint of (MSIS) Infection Infectious Society Diseases (EBJIS) (SOSSID) n= n= Infectious Diseases Society of America (IDSA) n= 55 Renz N et al. J Bone Joint Surg 2018

11 Individualized approach To relieve pain To preserve joint function To prevent future revisions Goals Confirm or exclude septic etilogy Define the least invasive surgical procedure leading to best results (Identify pathogen) Diagnostic work-up

12 Preoperative Intraoperative Intraoperative sampling History & examination Joint aspiration Imaging microbiology histopathology cytology microbiology cytopathology Sonication Laboratory

13 Diagnosis Is it an infection? Is it acute or chronic? Which pathogen?

14 Classification: acute & chronic Acute Time after implantation <1 month 3 36 months Any time Type of infection Early postoperative Delayed (low grade) Late Route Perioperative Haematogenous Signs Acute: fever, effusion, warmth, dehiscence Chronic: Persistent pain, loosening, sinus tract Acute or subacute Pathogen S. aureus Streptococci Enterococci Staph. epidermidis Cutibacterium acnes S. aureus E. coli Streptococci Chronic

15 Diagnostic approach Acute infections Early postoperative Chronic infections With sinus tract With loose prosthesis Late acute onset With stable prosthesis

16 Acute symptoms Early postoperative (<4 weeks) Late acute onset (any time) Leukocyte count not helpful (threshold unclear (>10,000 /μl) Parvizi J, J Arthroplasty 2014, Bedair H, CORR 2011 Alpha defensin as a confirmatory test? Renz N, J Bone Joint Surg 2018 Mostly hematogenous Zimmerli W, NEJM 2004 blood cultures (Joint aspiration) Debridement & prosthesis retention: intraoperative tissue cultures, sonication

17 Early postoperative PJI: prolonged discharge Exclude other reasons of prolonged discharge ( coagulopathy, hematoma, albumin deficiency) No reliable preoperative diagnostic test exist Revision & change mobile parts when discharge >5-10 days

18 Intraoperative diagnostics in early PJI 498 patients with prosthetic failures PJI defined according to modif. IDSA criteria Fernández-Sampedro M, BMC Inf Dis 2017

19 Pathogenesis of PJI Contiguous spread from adjacent infected tissue Postoperative (early & delayed) 5% 20% Hematogenous spread from a distant focus 75% Rakow A, Renz N et al. JBJS (in review)

20 Acute symptoms Early postoperative (<4 weeks) Late acute onset (any time) Leukocyte count not helpful (threshold unclear (>10,000 /μl) Parvizi J, J Arthroplasty 2014, Bedair H, CORR 2011 Alpha defensin as a confirmatory test? Renz N, J Bone Joint Surg 2018 Mostly hematogenous Zimmerli W, NEJM 2004 blood cultures (Joint aspiration) Debridement & prosthesis retention: intraoperative tissue cultures, sonication

21 Late acute PJI: primary infection sources 1 (+3?) colon adenoma 1 GI bleeding 2 GI infections Gastrointestinal tract, 7 Others, 3 1 contralat. PJI 1 pneumonia 1 epidural abscess 7 dental treatments 5 dental infections Oral cavity, 12 Unknown, 34 Urogenital tract, 12 2 manipulations 10 infections Skin and soft tissue, 16 Cardiovascular system, 22 n =106 9 skin erosion (pedicure, skin disease, chronic ulcers) 7 skin and soft tissue infections 14 endocarditis 5 infected CIED 3 catheter infections Rakow A, Renz N et al. JBJS (in review)

22 Investigation of primary focus Pathogen Source Diagnostics Staphylococci Blood cultures Echocardiography (TEE) Skin examination Streptococci S. oralis/mitis S. agalactiae S. dysgalactiae S. bovis/gallolyticus Orthopantomogram (OPTG), dentist, TEE Urinanalysis, imaging abdomen, skin examination, OPTG Colonoscopy Enterococci Urinanalysis TEE Enterobacteriaceae Urinanalysis CT Abdomen Renz N, Chirurg, 2017

23 Chronic complaints Acute infections Early postoperative Chronic infections With sinus tract With loose prosthesis Late acute onset With stable prosthesis

24 Chronic painful joint with sinus tract Infection confirmed Osmon, CID 2013, Parvizi CORR 2011 Leukocyte count not reliable Renz N, J Bone Joint Surg 2018 Swab culture not sensitive nor specific Tetreault MW, J Arthroplasty 2013 Revision surgery needed Zimmerli W, NEJM 2004 Intraoperative diagnostics (periprosthetic tissue & histology)

25 Chronic complaints Acute infections Early postoperative Chronic infections With sinus tract With loose prosthesis Late acute onset With stable prosthesis

26 AAOS Clinical Practice Guidelines Dogmas, personal Diagnosis opinions of PJI, 2010 and misleading information Every painful joint should be aspirated!

27 History: age of the prosthesis 16% Kaplan-Meier analysis of 112 prostheses 69% 2 years Portillo ME, CORR 2013

28 Routine synovial fluid tests Analysis of synovial fluid of 142 patients with prosthetic failure Diagnostic test Aseptic failure (n = 65) PJI (n = 77) sensitivity (%) specificity (%) Culture (n = 142) 1/65 40/77 52% 98% Leukocyte count (n = 103) 2/47 48/56 82% 96% Morgenstern C, DMID 2017

29 Which leukocyte cut-off is accurate? Author Schinsky MF, /201 (hips) Cipriano CA, 2008 Zmistowski B, (knees) Trampuz A, /133 (knees) Dinneen A, 2013 Patients (No. & joint) 146/810 (hips & knees) 34/75 (hips &knees) Ghanem E, /429 (knees) 1 Lc count = leukocyte count ( /μl) PMN = polymorphonuclear cells (%) Variable 1 Sensitivity Specificity Lc count > PMN > Lc count > Cut-off for PJI: PMN >78% Lc count > >2000 leukocytes/μl or >70% granulocytes PMN >75% Lc count > PMN >65% Lc count > PMN >65% Lc count > PMN >64% Trials which applied sonication

30 Leukocyte count: not always reliable False high Postoperative (<6 weeks) Rheumatologic disease Dislocation/periprosthetic fracture Metallosis False low Sinus tract Low-virulent pathogens, Candida

31 Biomarkers Wouthuyzen-Bakker M, Bone Joint J 2017 Shafafy R, Bone Joint J 2015 Frangiamore SJ, J Arthroplasty 2016 Shahi A, J Bone Joint Surg (Am) 2017

32 Renz N et al. JBJS 2018 (May 2)

33 Percent Percent Percent Percent Test performance with different definition criteria Alpha defensin lateral flow test Performance Leukocyte esterase Leukocyte esterase strip test Sensitivity 100 Specificity MSIS IDSA EBJIS SOSSID MSIS MSIS IDSA EBJIS SOSSID Applied definition criteria Applied definition criteria Sensitivity Specificity Depending on the definition criteria, the performance of tests varies widely! MSIS IDSA SOSSID Applied definition criteria Renz N et al. J Bone Joint Surg 2018

34 Comparison with leukocyte count PJI cases (based on EBJIS) (result within 10 minutes) (result within 2-4 hours) Applying proposed EBJIS criteria, leukocyte count showed significantly higher sensitivity than alpha defensin, especially in chronic infections Renz N. JBJS 2018 (in press)

35 Synovial fluid D-lactate Lactic acid L-lactate is constantly produced during metabolism and exercise D-lactate is produced by bacteria as a product of bacterial fermentation D-Lactate production in mammals is extremely low, with normal serum concentrations in the nano to D-lactate concentration is increased to millimolar range (mmol) in bacterial infection. micromolar range (nmol - µmol). L. Szalay 2003; Sh.M. Smith 994 Wellmer A. 2001; Gratacós J. 1995

36 D-lactate (mmol/l) D-lactate in synovial fluid = bacteria-specific marker Sensitivity: 98% Specificity: 84% Cohort of 137 aseptic failures and 87 PJI (according to pebjis criteria) hip and knee prostheses cut off 1, AF PJI Karbysheva S., Charité (in preparation)

37 Percentage PCR in synovial fluid Sensitivity Specificity PCR + PCR - Culture + 33 S. aureus (2) S. mitis/oralis (2) E. coli (1) E. faecalis (1) Leukocyte count (n=103) Culture (n=142) PCR (n=142) Culture - C. acnes (4) CNS (6) P. aeruginosa (1) S. pyogenes (1) Abiotrophia spp. (1) 25

38 Diagnostic algorithm for chronic symptoms Clinical examination Laboratory testing (CRP) X-ray (prosthesis) * no Joint aspiration: - Leukocyte count/differential - Microbiology (culture) Sinus tract? yes * Consider other reasons: - Aseptic loosening - Periprosthetic fracture - Dislocation - Muscular pathology - Wear - Metallosis Leukocyte count or culture consistent with infection? yes Septic revision of prosthesis with intraoperative diagnostics 3 no Persistent suspicion of infectionor high level of suffering? yes Prosthesis loose? yes no no Repeat diagnostic aspiration 3 months later Consider arthroscopic or open biopsy 5 PRO IMPLANT Foundation pocket guide, version 8 (modified)

39 Open or arthroscopic tissue biopsy Sensitivity rises only 18% compared to joint aspiration (if no implant is sent to sonication) interface is difficult to reach Fink CORR 2012 Allows exclusion of other pathologies (metallosis, tumor, rheumatologic diseases) Rarely needed; consider alternatively re-aspiration after 3 months Only in cases with high suspicion of PJI, negative preoperative diagnostics (eg punctio sicca), stable prosthesis and high level of suffering of the patient

40 Intraoperative diagnostics Superior to preoperative diagnostics Microbiology 3 samples Representative area 14d incubation (PCR) Histopathology SLIM-classification after Krenn and Morawietz CD15-Score Sonication Culture (PCR)

41 Marker of granulocytes: CD 15 Score Cut-off: 39cells/HPF Cut-off: 106cells/HPF

42 Diagnosis Is it an infection? Is it acute or chronic? Which pathogen?

43 Intraoperative tissue culture Obtain 3 tissue specimens - Interface tissue-prosthesis, no swabs - For culture and histology - Prolonged incubation: 14 days 14 d - Culture sensitivity: 60-80% Schäfer P. Clin Infect Dis 2008

44 Sonication of implants Removed implants Vortex, 30 s Sonication, 1 min, 40 khz May 2005 Feb 2007 Standard method ( 3 tissue biopsies) Tissue Sonicate Trampuz A et al. N Engl J Med 2007;357:

45 Improved sensitivity (>90%) Quantitative (more specific) Mixed infections (30%) Faster, less expensive Tissue biopsy Sonication fluid

46 Conclusion: Patient-tailored diagnostics Acute infections Early postoperative Chronic infections With sinus tract Preoperative diagnostics are of little importance focus on intraoperative diagnostics Late acute onset (hematogenous) Blood cultures and investigation of primary infectious focus Invisible PJI with loose or stable prosthesis Joint aspiration = most important preoperative diagnostic step Focus on intraoperative diagnostics (tissue culture, sonication, histology) Test performance of investigated tests depends on definition of PJI

47 Aim of today s talk Infection is the best possible complication, if appropriate diagnostic is combined with correct surgery and efficient anti-biofilm agents. Cure rate >90%

48 Pocket Guide:

49 Pocket Guide:

50 Workshops:

51 EUROPEAN BONE AND JOINT INFECTION SOCIETY 6-8 SEPTEMBER HELSINKI, FINLAND The conference will be held in the white marble and granite faced Finlandia Hall. The congress venue is situated beautifully in a park near the sea in the centre of Helsinki, in the vicinity of several hotels. DEADLINES ABSTRACT SUBMISSION: 20 APRIL 2018 EARLY REGISTRATION: 1 JULY 2018 We look forward to welcoming you to Helsinki!

52 Thank you Focus on implant, bone and joint-associated infections: Surgery: New concepts (retention, 1-stage, 2-stage short interval) Diagnosis: Fast innovative methods Antibiotics: Active against biofilms

53

54 Modern concepts