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HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Fungal Infections Daniel Kendoff.

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Presentation on theme: "HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Fungal Infections Daniel Kendoff."— Presentation transcript:

1 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Fungal Infections Daniel Kendoff

2 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Background: Incidence of periprosthetic infection ≈ 0,5 – 4% (Adeli & Parvizi, 2012) Periprosthetic Fungal Infections are REALLY rare Problems: No guidelines regarding diagnosis & therapy surgical treatment? topical / systematic drug therapy? Often not (initialy) diagnosed

3 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg International Consensus Group on Periprosthetic Joint Infection July 31- August 1, 2013 Thomas Jefferson University, Philadelphia Workgroup 13: Management of Fungal or Atypical Periprosthetic Joint Infection Liaison: Matthias Gebauer MD, HELIOS ENDO-Klinik, Hamburg Leaders: Lars Frommelt MD, HELIOS ENDO-Klinik, Hamburg Delegates: Pramod Achan MBBS, Tim N Board MD, Janet Conway, William Griffin MD, Nima Heidari MBBS, Glenn Kerr MD, Alex McLaren MD, Sandra Bliss Nelson MD, Marc Nijhof, Akos Zahar MD

4 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Question 1: What is the definition of fungal or atypical periprosthetic joint infection (PJI)? Consensus: A fungal or atypical PJI is an infection of a joint arthroplasty caused by fungi or atypical bacteria. Delegate Vote: Agree: 89%, Disagree: 7%, Abstain: 4% (Strong Consensus)

5 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Definition: Periprosth. Fungal Infection are diagnosed, if one of the following facts are given ( referring to the definition of bacterial PJI by the Workgroup Convened by the Muskuloskeletal Infection Society, 2012) Positive fungal growth in synovial fluid or intraop. samples (≥ 2x) Sinus with fungal growth in the sample Or 4 of the following 6 points: Elevated BSG or CRP Elevated White Blood Cell Count (WBC) Elevated Cell Count in synovial fluid Aspiration of pus Detection of antigen of fungal organism in one of the probe > 5 Neutrophile/ HPF in 5 HPF with 400x magnification CAVE: Periprosth. Fungal Infection may present just with mild symptoms (!!!)

6 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Diagnostic – Symptoms: Screen of ALL Literature

7 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Diagnostics: Laboratory Infections Parameters CRP↑, ESR ↑, WBC ↑ X-Ray Radiolucency? Joint aspiration ≥ 2x (in absence of systemic antifungal therapy) Cave: Culture time, Culturefluid (!) Intraop. Samples in case of doubt

8 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Diagnostics Clin Orthop Relat Res Apr 18. Systemic Inflammatory Markers and Aspiration Cell Count May Not Differentiate Bacterial From Fungal Prosthetic Infections. Bracken CD, Berbari EF, Hanssen AD, Mabry TM, Osmon DR, Sierra RJ. NO Difference in CRP, Leukos and ESR Between FUNGAL & Bacterial PJI

9 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Standard culture medium Mikrobiologic expertise special culture medium

10 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Question 3: Which host factors (concomitant disease and other factors) predispose to fungal PJI? Consensus: Predisposing host factors to fungal PJI are: decreased cellular immunity, immunosuppression, neutropenia, malignancy, antineoplastic agents, corticosteroids or other immunosuppressive drugs, drug abuse, prolonged use of antibiotics, presence of indwelling catheters (intravenous, urinary or parenteral hyperalimentation), diabetes mellitus, malnutrition, rheumatoid arthritis, history of multiple abdominal surgeries, history of renal transplantation, severe burns, acquired immunosuppressive disease, tuberculosis, and preceding bacterial infection of the prosthesis. Delegate Vote: Agree: 95%, Disagree: 2%, Abstain: 3% (Strong Consensus)

11 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Concomitant diseases:Σ% Diabetes1021,74 Autoimmune diseases613,04 Prior PJI with prolonged antiobiotic therapy1021,74 Drug-induced immunosuppression715,22 Malignant diseases48,70 HIV12,17 NR919,57 None1123,91 Screen of ALL Literature

12 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Organisms

13 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Surgical treatment: EARLY Infection Preservation of the prothesis, debridement + lavagé with/without topical antifungal agent LATE Infection Removal of the prosthesis one- vs. two-stage arthrodesis resection arthroplasty

14 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Question 5: What is the best way to surgically manage fungal PJI: irrigation and debridement, one-stage exchange, two-stage exchange, or permanent resection arthroplasty? Consensus: On the basis of the current literature, two-stage exchange arthroplasty is the recommended treatment option to manage fungal PJI. However, the success rate is lower than that of bacterial cases. Delegate Vote: Agree: 95%, Disagree: 2%, Abstain: 3% (Strong Consensus)

15 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg

16 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Therapy– antifungal drugs Topical antifungal therapy intraarticular powder 100mg amphotericin, amphotericin B and itraconazole ( Cave: liposomal for local delivery ) lavage (fluconazole 200mg/d). Systemic antifungal therapy: - Fluconazol (Cave low sensitivity of Candida) - Amphotericin - 5-Flucytosine,Itraconazole, Ketoconazole, Voriconazole - Caspofungin and other Echinocandine

17 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg

18 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Cementspacer Amphotericin B or Azole

19 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Question 7: When treating fungal PJIs in a staged fashion, which antifungal or antibacterial medications should be used for the cement spacer? What is the recommended dose? Consensus: Recent literature confirms that antifungal agents are released in high amounts for local delivery, but there are no clinical studies yet to document the clinical effectiveness. The use of liposomal amphotericin B, loaded in bone cement, has more than an order of magnitude greater release than conventional amphotericin B deoxycholate. There is also controlled release data for azol antifungals, with specific data on the elution of voriconazol from bone cement. There should be a consideration for adding an antibacterial to the bone cement for local delivery in addition to the antifungal. Delegate Vote: Agree: 94%, Disagree: 2%, Abstain: 4% (Strong Consensus)

20 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Question 8: Which investigations are recommended to monitor fungal PJI and determine timing of reimplantation ? Consensus: C-reactive protein and erythrocyte sedimentation rate are recommended to monitor fungal PJI. There is no clear evidence for the timing of reimplantation based on laboratory tests. Delegate Vote: Agree: 89%, Disagree: 8%, Abstain: 3% (Strong Consensus)

21 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Question 9: What is the duration for systemic antimicrobial (antifungal) agent administration in the treatment of fungal PJI? Consensus: Systemic antimicrobial (antifungal) agent administration in the treatment of fungal PJI should be started at the time of removal of the implants (stage one) and continued for at least 6 weeks. It should then be stopped before reimplantation (stage two) the timing of which is based on clinical judgement and laboratory tests. There are no good data to support antifungal agent administration after reimplantation. Delegate Vote: Agree: 85%, Disagree: 10%, Abstain: 5% (Strong Consensus)

22 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg

23 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Retrospective elective study 14 consecutive patients (9 male) mean age 68.3 (31-87) years Follow up of 7 (3-11) years 4 Pat. lost to follow up 10 Total Hip Arthroplasties 7 patients history of two-stage exchange due to bacterial or suspected bacterial infection onset symptoms mean 6.7 (1-26) months after last surgery Pain and loss of function in all patients nocturnal fever and unwanted weight loss 2 patients 5 patients presented fistula mean preoperative CRP 22 ( ) mg/L mean preoperative WBC 5.7 ( ) /nl

24 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg All patients were treated by single stage revision No antifungals were admixed to bone cement Anti-fungal therapy started the evening before surgery in azoles In amphothericin B + flucytisine: surgery after saturation Therapy in outpatient means sequential therapy after IV- Therapy

25 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg PatientBacterial spectrum of former PJI (external result) Fungal spectrum of former PJI (external result) Pre-operative joint aspiration (internal result) Intra-operative probe (internal result) Samples in case of re-/ new infection (internal result) Intravenous antifungal therapy Oral antifungal therapy 1Strep. spec.C. albicans noneFluconazole 2nonenoC. albicans noneFluconazole Ampho. B Fluconazole 3nonenoC. glabrata noneFlucytosin Ampho. B Fluconazole 4MRSA, Ser. marcescens C. albicans Stap. aureusnoneFlucytosin Ampho. B none 5NAnoC. albicans noneVoriconazole 6Strep. spec.noC. albicans noneFlucytosin Ampho. B Fluconazole 7nonenoC. parapsilosis Stap.epidermidis Flucytosin Ampho. B none 8Stap. capitisnoC. parapsilosis noneFlucytosin Ampho. B none 9Stap. aureus Strep. mitis C. lusitaniae noneVoriconazole 10Strep. spec.C. parapsilosis noneFlucytosin Ampho. B none

26 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg 1 recurrent infection after 2 mths 3 revsions due to other reason: Recurrent Dislocation (1 pat) Delayed wound healing and Periprosthetic Fracture (1 pat)

27 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg At the latest follow up: No relevant radioloucency CRP <5.0 mg/l WBC 6.2 cells/nl ** HHS HSS

28 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg Conclusion Fungal PJI are rare No consensus regard treatment Gold-Standard = two-stage exchange Topical antifungal treatment possible Duration of Antifungals 6 weeks…

29 HELIOS ENDO-Klinik Hamburg Helios ENDO-Klinik Hamburg THANK YOU


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