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Periprosthetic Fungal Infections are REALLY rare

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Presentation on theme: "Periprosthetic Fungal Infections are REALLY rare"— Presentation transcript:

0 Fungal Infections Daniel Kendoff

1 Periprosthetic Fungal Infections are REALLY rare
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

2 Thomas Jefferson University, Philadelphia
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

3 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)

4 Positive fungal growth in synovial fluid or intraop. samples (≥ 2x)
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 (!!!)

5 Screen of ALL Literature
Diagnostic – Symptoms:

6 Laboratory Infections Parameters CRP↑, ESR ↑, WBC ↑ X-Ray
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

7 NO Difference in CRP, Leukos and ESR Between FUNGAL & Bacterial PJI
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

8 Standard culture medium
Mikrobiologic expertise special culture medium

9 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)

10 Screen of ALL Literature
Concomitant diseases: Σ % Diabetes 10 21,74 Autoimmune diseases 6 13,04 Prior PJI with prolonged antiobiotic therapy Drug-induced immunosuppression 7 15,22 Malignant diseases 4 8,70 HIV 1 2,17 NR 9 19,57 None 11 23,91

11 Organisms

12 Surgical treatment: EARLY Infection LATE 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

13 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)

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15 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

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17 Amphotericin B or Azole
Cementspacer Amphotericin B or Azole

18 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)

19 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)

20 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)

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22 Retrospective elective study 14 consecutive patients (9 male)
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 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

23 No antifungals were admixed to bone cement
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

24 Patient Bacterial 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 1 Strep. spec. C. albicans none Fluconazole 2 no Ampho. B 3 C. glabrata Flucytosin 4 MRSA, Ser. marcescens Stap. aureus 5 NA Voriconazole 6 7 C. parapsilosis Stap.epidermidis 8 Stap. capitis 9 Strep. mitis C. lusitaniae 10

25 1 recurrent infection after 2 mths 3 revsions due to other reason:
Recurrent Dislocation (1 pat) Delayed wound healing and Periprosthetic Fracture (1 pat)

26 No relevant radioloucency
At the latest follow up: No relevant radioloucency CRP <5.0 mg/l WBC 6.2 cells/nl ** ** HHS HSS

27 Conclusion Fungal PJI are rare No consensus regard treatment Gold-Standard = two-stage exchange Topical antifungal treatment possible Duration of Antifungals 6 weeks…

28 THANK YOU


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