Periprosthetic Joint Infection What is on the horizon
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1 Periprosthetic Joint Infection What is on the horizon Javad Parvizi MD, FRCS Rothman Institute at Thomas Jefferson University, Philadelphia
2 Research support: NIH OREF Stryker Orthopedics Depuy Zimmer Baxter 3M Biomemetics Ceramtec Smith and Nephew Board Member/Adviser Journal of Arthroplasty Philadelphia Orthopaedic Soc Eastern Orthopedic Assoc. United Healthcare Magnifi Group (Publishers) 3M JBJS-A Disclosures Consultant: Zimmer Smith and Nephew Convatech TissueGene Ceramtec OsteoMEM 3M Cadence Intellectual Property/Royalty:/Ownership SmarTech Elsevier Wolters Kluwer Slack Hip Innovation Technology CD Diagnostics Jaypee publishers Datatrace Rothman Institute Orthopaedics Thomas Jefferson University
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4 Periprosthetic Joint Infection Incidence 1-4% of primary May lower occur limb in arthroplasties > 30% after revision arthroplasty Rothman Institute Orthopaedics Thomas Jefferson University
5 THA Infection: Medicare Data Rothman Institute Orthopaedics Thomas Jefferson University
6 TKA Infection: Medicare Data Rothman Institute Orthopaedics Thomas Jefferson University
7 Infected Revisions: Kurtz, S, Parvizi J JOA 2008
8 Infected Revisions Cost THA TKA Total THA + TKA Total Cost (millions) of Patients with Infected Procedures Year
9 Infected Revisions Burden
10 Annual Cost $600 Million Rothman Institute Orthopaedics Thomas Jefferson University
11 Periprosthetic Joint Infection Prevention Diagnosis Treatment
12 Periprosthetic Joint Infection Prevention of SSI
13 Prevention of PJI Optimize Host
14 Diabetes Control of glucose HbA1C <7% glucose <180 Ulcerations Neuropathy
15 Control Nidus GI/GU (urine) Skin/nails No role for routine dental clearance
16 Rheumatoid Arthritis Disease modifying agents (antimonoclonal antibodies) Steroids (taper) Skin (ensure there is no ulcers)
17 Preoperative Optimization Malnutrition Obesity Skin (psoriasis, eczma, ulcerations) Vascular insufficiency?? Smoking
18 Peri-operative Factors Skin prep Gloves Draping Room Antibiotics Exposure Bleeding control Closure Dressing
19 Antibiotics
20 Prevention of PJI Antibiotics Prophylactic antibiotics Vancomycin (needs 1 hour) MRSA carriers Remote or recent MRSA Infection Institutionalized patients Healthcare workers
21 Skin Prep Starts at home
22 Preoperative Optimization Skin decontamination Betadine shower Chlorhexidine wipes/showers Shaving (save until the OR)
23 Skin Prep Skin prep 9 step Matar W, et al JBJS 2012 Skin prep Most important agent is ALCOHOL
24 Skin Prep Contamination of skin during draping May repeat skin prep (Duraprep TM )
25 Drapes Skin recolonizes Adhesive draping Johnston DH, et al: Br J Surg 74:64, 1987
26 OR Environment Lack of adequate science Laminar flow Space suits Size/volume
27 OR Environment Wound Contamination Direct Fall-out Gloves Or Instruments The Primary Source Of Bacteria In OR Is OR Personnel
28 OR Environment People Shed up to 10,000 bacteria/min. Dispersers 13% of Men 5% of Post-menopausal Woman 1% of Pre-menopausal Women Traffic--- terrible
29 Gloves Puncture all cases > 3 hrs Cotton outer gloves reduce risk Change every 2 hrs
30 Approach Gentle soft tissue handling Expeditious surgery Irrigation
31 Wound Complications Drainage Hematoma Cellulitis Treat Aggressively
32 Hip do not lie
33 Anticogulation Aspirin for majority As effective as any agent Less complication
34 SSI caused by MRSA Screening and Decolonization?
35 Point of care Handheld PCR Machines Portable Isothermal Recombinase polymerase amplicaifcation (RPA) Rothman Institute Orthopaedics Thomas Jefferson University
36 Microbead Detector (RapiDetect) ABSENT PRESENT anchor PATCH peptide substrate reporter molecules PoC Peptide covalently attached to microbead anchor and reporter molecule Rothman Institute Orthopaedics Thomas Jefferson University
37 Decolonization One time application One hour before surgery 12 hour effect 99% eradication Lowers SSI Phillips MS et al. IDSA 2012 Rothman Institute Orthopaedics Thomas Jefferson University
38 Anti-Staphylococcal Drug XF-73 I. a dicationic porphyrin drug II. III. rapid Gram-positive antibacterial activity unique abilities to prevent bacterial resistance IV. may be used to prevent potentially fatal SA infections V. undergoing clinical trials for the nasal decolonization of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA)
39 Screening It appears that screening and decolonization reduces the incidence of SSI Logistic issues How to? Perhaps most important is identifications Appropriate antibiotics Isolation Stay tuned
40 Periprosthetic Joint Infection Prevention Diagnosis Treatment
41 Diagnosis of PJI No absolute test for diagnosis No standard definition/criteria for PJI
42 Culture gold standard Advantages Inexpensive Result can be used in further testing Disadvantages Polymicrobial results Time limitations - pathogen growth - result to treatment False positive - contamination False negatives - biofilms - prior antibiotic treatment - hard-to-culture organisms Malekzadeh CORR 2010
43 Definition of PJI (MSIS) There is a sinus tract communicating with the prosthesis; or Parvizi J et al CORR 2011 Rothman Institute Orthopaedics Thomas Jefferson University
44 Definition of PJI (MSIS) There is a sinus tract communicating with the prosthesis; or A pathogen is isolated by culture from at least two separate tissue or fluid samples obtained from the affected prosthetic joint; or Parvizi J et al CORR 2011 Rothman Institute Orthopaedics Thomas Jefferson University
45 Definition of PJI (MSIS) There is a sinus tract communicating with the prosthesis; or A pathogen is isolated by culture from two separate tissue or fluid samples obtained from the affected prosthetic joint; or When four out of the following six criteria exists Parvizi J et al CORR 2011 Rothman Institute Orthopaedics Thomas Jefferson University
46 ESR or CRP, synovial WBC count, synovial PMN%, Presence of purulence, Isolation of a microorganism in one culture of periprosthetic tissue or fluid, or 5 neutrophils per hpf in 5 hpf observed from histological analysis of periprosthetic tissue at x 400 times magnification. Definition of PJI Rothman Institute Orthopaedics Thomas Jefferson University
47 AAOS Guidelines Craig Della Valle Javad Parvizi Mark Spangehl Tom Bauer Paul DiCesare Richard Evans John Segreti AAOS Guideline Committee Rothman Institute Orthopaedics Thomas Jefferson University
48 AAOS Guidelines 15 recommendations Majority strong or moderate Review of literature Rothman Institute Orthopaedics Thomas Jefferson University
49 AAOS Guidelines Patients were divided into high and low risk groups (consensus) ESR and CRP for all patients undergoing revision arthroplasty Aspiration of joint before any further imaging Rothman Institute Orthopaedics Thomas Jefferson University
50 AAOS Guidelines Patients be off antibiotics before apsiration (2 weeks) No Antibiotics until diagnosis reached or refuted No role for intraoperative gram stain Rothman Institute Orthopaedics Thomas Jefferson University
51 AAOS Guidelines Cannot recommend bone scan, CT, or MRI Frozen section for suspected but not confirmed cases Perioperative antibiotic not to be witheld Rothman Institute Orthopaedics Thomas Jefferson University
52 Rothman Institute Orthopaedics Thomas Jefferson University
53 Experimental Investigations Polymerase Chain Reaction Target: Segment of the 16S ribosomal RNA gene unique to eubacteria Report: Sensitivity 100% Specificity 89% (Mariani & Tuan 1985 Tuan et al JBJS 2008) Rothman Institute Orthopaedics Thomas Jefferson University
54 Rationale Protein profiling has been successfully used to diagnose Pregnancy Urinary tract infections Inflammatory proteins elevated in cases of PJI in both Serum, and Synovial fluid Di Cesare JBJS 2007 Shah CORR 2009 Deirmengian CORR 2010
55 Pregnancy Test for PJI Neutrophil enzymes Detected in joint aspirate 1 minute for response
56 Leukocyte esterase in Urinalysis strips
57 Results Prospective study Rothman Institute 31 infected / 83 uninfected * sensitivity = 81% * specificity = 100% * positive predictive value = 100 % * negative predictive value = 93.3 % Parvizi et al. JBJS 2011 Rothman Institute Orthopaedics Thomas Jefferson University
58 ROC The Area under the Curve (AUC): 0.988
59 Simple Test Leukocyte esterase strip test is highly accurate for diagnosis of PJI Fast (real time), simple, cheap
60
61 RBM Analytes (Categorical) Category Cytokines Adhesion Molecules Growth Factors Acute-phase reactants Complement cascade Chemotactic proteins Metalloproteinase compounds Lysis/Destruction Other Proteins IL-1α, IL-1β, IL1ra, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 subunit p40, IL-12 subunit p70, IL-15, IL-17, IL-23, IFN-γ, TNF-α, TNF-β, TNF receptor-like 2 ICAM-1, Vascular Cell Adhesion VEG-F, BDNF CRP Complement C3, α-2 macroglobulin, Beta-2-Microglobulin, von Willebrand Factor, Fibrinogen, Factor VII Monocyte Chemotactic Protein 1, Eotaxin-1 MMP-2, MMP-3, MMP-9, TIMP-1 Alpha-1-Antitrypsin, Granulocyte-Macrophage Colony- Stimulating Factor, Macrophage Inflammatory Protein-1 alpha Macrophage Inflammatory Protein-1 beta Ferritin, Haptoglobin, Stem Cell Factor, T-Cell-Specific Protein, RANTES, Molecule-1, Vitamin D-Binding Protein
62 Rothman Institute Orthopaedics Thomas Jefferson University
63 Recursive Partitioning
64 Is it really infected? Rothman Institute Orthopaedics Thomas Jefferson University
65 Novel Molecular System IBIS T5000 Biosensor 1) Amplification Multiple pairs of species specific primers 2) ESI-MS: Electrospray Ionization Mass Spectrometry 3) Base composition analysis compared to database 4) Microorganisms identified Pathogen status Genomes/Well Confidence meca gene Rothman Institute Orthopaedics Thomas Jefferson University
66 IBIS 5000: Step 1 Sample Prep and Broad Range PCR Rothman Institute Orthopaedics Thomas Jefferson University
67 IBIS 5000: Step 2 MS Analysis and Signal Processing Rothman Institute Orthopaedics Thomas Jefferson University
68 IBIS 5000: Step 3 Triangulation Using Multiple Primers Primer #1 Mass Base Count Primer Primer Blue Set Mass Set Mass Base Base A Count 12 Count G 17 C 17 T 13 Primer Blue Blue Set Mass Base A 12 ACount G 17 C 17 T 13 Primer Blue Set Mass Base A 12 Count G 14 G 17 C 14 C 17 T 12 T 18 Blue Blue Blue A 13 A 12 G AG C 14 C 17 T 12 T 18 Blue A 13 Blue Blue A 12 AG 14 G 11 G 17 C 14 C 19 C 17 T 12 T 15 T 15 Blue Blue A G AG C 19 C 12 T 15 T 15 Blue A 18 Blue Blue A 14 AG 11 G 11 G 14 C 19 C 17 C 12 T 15 T 16 T 14 Blue Blue A 15 Blue AG AG C 17 C 15 T 16 T Blue Blue A 11 AG 11 G 18 G 19 C 17 C 15 C Blue A 15 T 16 T 15 T Blue AG 18 G 17 C 15 C 16 T 15 T Blue Blue A 11 AG 18 G 17 C 15 C 16 T 15 T G 15 C 15 T 13 Blue A 18 G 15 C 15 T 13 Rothman Institute Orthopaedics Thomas Jefferson University
69 Organisms Profile H. influenzae [A28 G28 C25 T20] S. pyogenes [A27 G32 C24 T18]
70 Novel Molecular System PLEX-ID 1) Amplification Broad identifiction (3100 species) 2) Targeted identification (spectrosray) 1) Characterization (high resolution subtyping and drug resistance) Pathogen status Genomes/Well Confidence meca gene Rothman Institute Orthopaedics Thomas Jefferson University
71 Periprosthetic Joint Infection Prevention Diagnosis Treatment
72 Treatment of PJI Options Available Antibiotic suppression alone Debridement and antibiotics Prosthesis Removal One stage reimplantation Two stage reimplantation Arthrodesis Amputation
73 I&D for PJI Traditional Indications Revisited Azzam K JOA 2010
74 Debridement Indications Acute symptoms (<48 hr) Susceptible organism Good soft-tissue coverage Well-fixed prosthesis
75 I&D for Methicillin Resistant Organisms Success rates: 37% our experience 17% Salgado et al, CORR % Barberán et al, Am J Med % Kilgus et al, CORR 2002 Average success rate: 24%
76 Results True success rate (no infection, no mechanical failure, no reoperation) % Parvizi et al CORR 2009
77 Intracellular S. aureus in Periprosthetic Tissue Parham S et al, Clin Infect Dis 2006
78 New Antibiotics New Glucopeptides: dalbavancin, telavancin, oritavancin New betalactam: ceftobiprole New rifamycin: AB-0043 New inhibitor of DHFR: iclaprim
79 PBP Rothman Institute Orthopaedics Thomas Jefferson University JM
80 Staphylococcus aureus (MSSA) peptidoglycan PBP B-lactactam Rothman Institute Orthopaedics Thomas Jefferson University JM
81 Staphylococcus aureus (MSSA) peptidoglycan PBP B-lactam Rothman Institute Orthopaedics Thomas Jefferson University JM
82 Staphylococcus aureus (MRSA) peptidoglycan PBP 1 2 2a 3 4 B-lactam ceftobiprole Rothman Institute Orthopaedics Thomas Jefferson University JM
83 Staphylococcus aureus (MRSA) PBP 1 2 2a 3 4 B-lactam ceftobiprole Rothman Institute Orthopaedics Thomas Jefferson University JM
84 Rothman Institute Orthopaedics Thomas Jefferson University
85 Biofilm Smart Implants Natural barriers (opsonins, defensins) Biofilm disruption technologies Immunization fragments of RNA to elicit cellular immunity Staph aureus vaccine (University of Rochester/Pfizer)
86 Vancomycin Tethered To Ti Prevents Infection Parvizi J, et al. Clin Orthop 2004
87 Modification of Bone Allograft a. EDTA as needed AEEA Linker 2X Addition of Vancomycin Naturally-occurring amines in bone protein Addition of linkers Vancomycinmodified bone b. Fluorescamine c. Vancomycin Background Rothman Institute Orthopaedics Thomas Jefferson University Stained Control Modified
88 Bacterial Challenge: S. aureus Rothman Institute Orthopaedics Thomas Jefferson University
89 Cortical Bone Struts Control VAN-Bone 30 µm 30 µm Rothman Institute Orthopaedics Thomas Jefferson University
90 Anti-infective Coating N,N- dodecyl,methyl polyethylenimine (DM-PEI) Microbicidal bubble bursting porcupine Permanent Passive Coating Intra-operative dipping Non-leaching attachment Long chain polycationic molecules Disrupts lipid membranes or cell walls of bacteria U.S.S.N. 61/543,981 Antibacterial Coatings that Inhibit Biofilm Formation on Orthopedic and Dental Implants.
91 CSA-13 Developed by Dr. Paul Savage Synthetic analog of naturally occurring antimicrobial peptides (such as magainin-african Clawed Frog) Eradicates high inocula of bacteria including those in a biofilm Can be coated alone or with polymer conjugate onto the surface of metal or polymer Sterilized by ETO, gamma irradiation or autoclave Savage PB. Eur J Org Chem 2002;5: Chin JN, et al. Antimicrob Agents and Chemother 2007;51(4): Savage PB, et al. IFIC Conference
92 Musculoskeletal Infection Society International Consensus Meeting Review of literature(if available) Consensus/recomemndations 400 delegates/80 countries/societies Representation from FDA/CMS/NIH/NQF/AHRQ and so on Rothman Institute Orthopaedics Thomas Jefferson University
93 THANK YOU.
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