1. Microbiological Evaluation of PJIs Survey Results Lorenzo Drago IRCCS Galeazzi Institute – University of Milan

2. Dear ISOC Members, based on an initiative from the ISOC group during the last meeting in Hamburg, it was decided to send out a questionnaire to map the present microbiological routine used for the diagnosis of prosthetic joint infections. We would like to have only one answer from each ISOC unit. The answers will be aggregated and presented in Mexico. In addition the actual literature will be searched and a guideline document discussed in a workshop during the next ISOC meeting. Subsequently a document will be published on behalf of the ISOC group. Galeazzi Institute Ortho Dept Lund HSS

3. ADDRESS Economic Impact of PJIs - wrong or delayed diagnosis Questionnaire answers examination Improving and debating matters

4. Guest editorial Prosthetic joint infections – a need for health economy studies “An increase in the rate of revision due to infection…. Needs “A rapid economic evaluation….. “A clear and common definition of deep infection…... “No model can depict the numerous possibilities…….. Acta Orthopaedica 2014

5. Costs Influences in PJIs Factors related to the patients Revision Modalities Surgical management Strategy One-stage/two-stage

6. Economic burden of Hip PJI (UK) Vanhegan IS et al. J Bone Joint Surg 2012

7. Complications for infections Vanhegan IS et al. J Bone Joint Surg 2012 Indication Mean operating time Mean blood loss Complications rate Hospital stay Revision surgery +41%+160%+32%Generally longer

8. Hip cost Analysis IRCCS Galeazzi The case of hip prosthesis” (full cost) 4,1%0,2 % 41,7% 4,3% 19,5% 3,5 % Indirect costs 12,4% 14,4% COSTS % Instruments 0,2% Lab 3,5% Personnel 4,1% drugs 4,3% Consumables 12,4% Medical staff 14,4% Indirect costs 19,5% Prosthetic material 41,7% Total 100% Variable costs increase of 30-50%

9. Other relevant factors Microorganisms-Dependent Culture negative PJI Factors related to the virulence MDR pathogens

10. PJI The Economic Impact of Methicillin-Resistant Infections Parvizi J. et al. J Atrhoplasty, 2010 Irrigation and Debridment+ 74 Resection artrhoplasty+ 29 Revision (1-stage)+ 41 Reimplantation+ 30 Cost Per Procedure % Days in hospital per visit + 50% Days in hospital per patient + 78%

11. Microorganisms dependent factors Polymicrobial Infection + 41% Culture-Negative -29% Journal of Hospital Infection, 2013

12. False negative!!! Biofilm notably hinders sampling and culturing; Difficult to detach biofilm-embedded bacteria from prosthetic surfaces. ISSUES FOR ORTHO-MICROBIOLOGISTS! Up 30% of False Negative

13. Wrong or delayed diagnosis of PJIs What is the financial impact of wrong or delayed diagnosis of PJI? 

14. Wrong or delayed diagnosis of PJI Deterioration of bone Complications risk (i.e. Longer stay) Drugs (es. Antibiotics) Diagnostic procedures (i.e. Imaging) Loss of Medical Confidence Patient’s psycological consequences

15. AIM ISOC Questionnaire Mapping the microbiological routine used for the diagnosis of prosthetic joint infections.

16. ISOC Questionnaire

17. Diagnosis of PJI

18. Criteria for Diagnosis of PJI IDSA Presence of a sinus tract communicating with the prosthesis Same Presence of purulence without another known etiology surrounding the prosthesis Growth of virulent microorganisms in a single specimen MSIS Major criteria Same Minor criteria (3/5) CRP>10 mg/dL for acute CRP> 1 mg/dL - ESR >30mm/hr chronic Same Elevated WBC, PMN% and ++ leukocyte esterase in synovial fluid A single positive culture AAOS Positive cultures aspirate joint and elevated cell count/differential Two or more intraoperative cultures +/- yielding the same organism. ESR and CRP abnormal values Histopathology of periprosthetic tissue suggestive for acute inflammation

19. Criteria for PJIs diagnosis MSIS criteria: 5 Centers AAOS criteria: 7 Centers IDSA criteria: 1 Center 1 Center: Presence of a fistula or sinus tract and elevated WBC count in joint fluids 1 Center: Elevated ESR and CRP values + positive cultures from prosthetic joint drainage or sinus 1 Center: Fistula, positive joint fluid culture and wbc count

20. What cut-off levels of ESR and CRP do you consider significant to suspect a prosthetic infection? MSIS Chronic: ESR: >30mm/hr CRP>1mg/dL Acute: CRP>10mg/L

21. Do you consider the possibility of infection only in patients with abnormal ESR and/or CRP values? MSIS No: Clinical judgement should not be outweighed by use of diagnostic algorithm or any individual test

22. CRP LABORATORY TESTING Low levels of CRP may be found in infections with less virulent pathogens (Corynebacteria and Propionibacteria)

23. Joint aspiration prior to surgery in suspected infections

24. What cut-off value for WBC count and neutrophils percentage in joint aspirates do you consider suggestive for PJIs? MSIS Chronic: >3000 WBC >80% PMN Acute:>10000 WBC >90% PMN

25. Is joint aspiration enough to proceed with surgical treatment if it gives a positive culture?

26. Do you perform cultures from sinus tract in all patients? MSIS A sinus tract is pathognomonic finding for PJI. NO SWABS or CULTURE!!

27. Transport of samples to Laboratory

28. How many samples do you usually send for cultures? MSIS More than 3 but not more than 6

29. Do you take tissue samples with the same surgical instrument?

30. In your laboratory is sonication reserved to particular cases? MSIS Sonication should be limited to cases of suspected or proven PJI

31. Drago et al. Clin Orthop Relat Res. 2012 Jun 14. Is DTT method reproducible and comparable to the Sonication one?

32. Italian Association of Clinical Microbiologists AMCLI

33. Q8-9: Does your laboratory perform enrichment cultures and for how many days? MSIS 5-14 days or longer

34. Q10: What is your opinion about the use of molecular methods? PROs It may be useful in particular cases (n=7) – Difficult to grow microorganisms (n=7) – Suspected M. tuberculosis (n=3) CONs Oversensitive (n=4) – Risk of false positive results (no differences between live and dead microorganisms) No data on susceptibility pattern (n=1) Not useable in polymicrobic infections (n=1) Not usefu l (n=1) MSIS Nucleic acid based testing is not currently a recommended routine diagnostic test for PJI In cases of negative cultures or other diagnostic tests, molecular techniques may help identify the unknown pathogens

35. Q11-12:Use of molecular methods

36. Q13: Usefulness of preliminary report ALL: It is advisable to report isolation of each microorganism as soon as possible. A preliminary report for negative samples after 5 days may be useful for clinicians, followed by a conclusive report at the end of enrichment.

37. Conclusive Remarks “Moderate” concordance time to: Drafting a unique document Single Procedure Try to understand “discordances” Improve Methods and Procedures External Lab is a debating matter

38. Future “ISOC” Directions Create Epidemiological Database (Pathogens, Resistant %, Drugs used, Drugs rotation) Create “ISOC” Registry of Infections (per site, age, comorbidities) Create “ISOC” BIOBANK (study virulence, Biofilm, ATB susceptibility, new and old ATBs) Create New Fellowships (Microbiologists, Labs) NOT WITHOUT A UNIQUE MICROBIOLOGICAL AND LAB PROCEDURE!!!

39. ….many thanks to: All of you Thomas Sculco Ilsa Klinghoffer!!!