The role of oral antibiotics in Prosthetic joint infection. Matthew Dryden MD

Transcription

1 The role of oral antibiotics in Prosthetic joint infection Matthew Dryden MD

2 Persistence of bone infection Osteomyelitis in 1930

3 Prosthetic joint replacement demand is increasing

4 When things go wrong

5 Patient care decisions - Who decides? Surgeon specific Guideline driven

6 Rule of thumb When to start oral antibiotics in PJI IV days Oral 6-12 weeks THR Oral 6-24 weeks TKR Kim et al 2013 J Antimicrob Chemother doi: /jac/dkt374

7 Suspected prosthetic joint infection Managed by a consultant orthopaedic surgeon Multi-disciplinary support ID/micro Plastic surgery Physician Radiology Suspect infection sinus tract persistent wound over a joint replacement acute pain in a prosthetic joint joint is chronically painful or never right

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11 Diagnosis and Management of Prosthetic Joint Infection CID 2013:56

12 Treatment of PJI Following debridement and retention of prosthesis 2-6 weeks of pathogen-directed antimicrobial therapy (or highly bioavailable oral) + oral rifampicin THR 3 months oral combination therapy TKR 6 months oral combination therapy In patient or OPAT When oral?

13 Microbial aetiology of PJI Andrej Trampuza, Werner Zimmerlib SWISS MED WKLY ; :

14 Following removal of joint Four to 6 weeks of pathogen-specific intravenous or highly bioavailable oral antimicrobial therapy Diagnosis and Management of Prosthetic Joint Infection CID 2013:56

15 When is it safe to start oral Abx Eligible for oral switch Received intravenous antibiotics for >24 h Afebrile for >24 h (core temperature <38 C, tympanic) Stable clinical infection WBC count normalizing, WBC not <4 x 10 9 /L or >12 x 10 9 /L CRP reducing No unexplained tachycardia Systolic blood pressure >100 mm Hg Mertz et al J Antimicrob Chemother , Patient tolerates oral fluids/diet and able to take oral medications with no gastrointestinal

16 When to start oral therapy in PJI or how long is a piece of string? The experts decide

17 Animal studies - What to start? Kim et al 2013 J Antimicrob Chemother doi: /jac/dkt374

18 Monotherapy v Combination Rifampicin Fluoroquinolones Fusidic acid Trimethoprim/ sulfamethoxazole Tetracyclines Lincosamides Macrolides Linezolid Beta lactamases Streptograminins Fosfomycin Rifampicin combinations Fusidic acid combinations Fluoroquinolone combinations Kim et al 2013 J Antimicrob Chemother doi: /jac/dkt374

19 Oral companions to rifampicin or fusidic acid Penicillins amoxicillin, flucloxacillin Cephalosporins cephradine, cefalexin Quinolones ciprofloxacin, levofloxacin Doxycycline Cotrimoxazole Linezolid (monitor FBC, optic and peripheral neuritis etc,? levels reduced by rif) Soriano A, Gomez J, Gomez L, et al. Eur J Clin Microbiol Infect Dis 2007; 26:353 6.

20 Diagnosis and Management of Prosthetic Joint Infection CID 2013:56

21 Pharmacokinetics Antibiotic bone concentrations Breakpoint MICs (BSAC) Flucloxacillin Clindamycin Ceftriaxone Teicoplanin Levofloxacin Ciprofloxacin Rifampicin Ertapenem S. aureus 2mg/l 2mg/l 4mg/l 2mg/l 2 mg/l 1 mg/l 0.5 mg/l 0.12 mg/l Strep. pyogenes 1mg/l 0.5 mg/l 2 mg/l 1 mg/l 2 mg/l 0.5 mg/l 0.5 mg/l Data on serum/bone ratio from Penetration of Antibacterials into bone. Clin Pharmakokinetics 2009;48: serum serum serum/bone cancellous Antibiotic dose peak trough ratio bone peak bone trough reference Flucloxacillin 25mg/kg iv qds 125mg/l 10mg/l mg/kg 1.6mg/kg Frank 1988 Flucloxacillin 500mg po qds 15mg/l 2 mg/l mg/kg 0.34 mg/kg Kropec 1979 Clindamycin 600 mg iv 12mg/l 1.4mg/l mg/kg 0.4mg/kg Mueller 1999 Clindamycin 450 mg po 8 mg/l 0.9 mg/l mg/kg 0.3 mg/kg Mueller 1999 Teicoplanin 10mg/kg iv/od 50mg/l 20mg/l mg/kg 7 mg/l Nehrer 1998 Ceftriaxone 25mg/kg iv od 250mg/l 50mg/l mg/l 5mg/l Martin 1996 Ciprofloxacin 750mg bd 3.7 mg/l 0.6 mg/l mg/kg 0.1mg/l Massias 1992 Ertapenem 1g iv od 155 mg/l 1mg/l mg/kg 0.2mg/l Boselli 2007 Rifampicin 4 mg/kg po bd 4 mg/l 1mg/l mg/l 0.4mg/kg Sirot 1983 Linezolid 600 bd po 16 mg/l 4 mg/l 0.5 8mg/L 5 mg/l Dryden 2011

22 Chronic suppressive therapy Indefinite course Flucloxacillin, doxycycline, cotrimoxazole, cefalexin Rifampicin / fusidic acid - not alone Monitor efficacy and toxicity Certain patients esp those unsuitable for or refuse further exchange revision, excision arthroplasty, or amputation. Diagnosis and Management of Prosthetic Joint Infection CID 2013:56

23 Common antimicrobial for oral suppression therapy Diagnosis and Management of Prosthetic Joint Infection CID 2013:56

24 Mr JW - 75 Post R hip replacement Polio in 1940 s Left with some paralysis in L leg Had been great cricketer, became main Times cricket correspondent Consequent degenerative changes in L hip and spine Osteotomies and L hip replacement in 1960 s by Charnley

25 JW Charnley hip lasted 35 years+, cup broke Hip replaced. Difficult procedure but technically satisfactory Post op superficial wound infection July 2005 Some antibiotics -? Clindamycin orally for 2 weeks Staph. aureus res pen only isolated Aug 2005 wound breaking down, sinus

26 JW Rigors and sweats. CRP in 300 s. WBC 12.5 Started on long term Flucloxacillin plus rifampicin Night sweats and rigors resolved Aggressive wound care CRP slowly fell By April 2006 CRP normal for 1/12 and wound and sinus completely healed. No pain and full mobility in hip. XRay of hip stable.

27 JW April 2006 antibiotics stopped Mid May 2006 further rigors, night sweats. ESR 94, CRP 325 Complaining of back pain and some radiation down R leg; tender over lower thoracic vertebrae R hip: no pain, full mobility, wound healed Blood cultures negative Antibiotics restarted: oral fluclox and fusidin for 2/12, then switched to fluclox alone, eventually reducing to single daily dose MRI of back degenerative changes, no discitis

28 JW June 2006: JP Getty memorial cricket match in Oxford. JW guest speaker collapse. Seen by renal physician and said to be pulseless. Put in recovery position on floor. Vomited x1. Recovered and carried on with lunch! Readmitted Blood cultures negative Hip NAD IV flucloxacillin + rifampicin Admitted to still getting night sweats on Abx but CRP down to 40

29 JW 85 Lifelong flucloxacillin Since then. JW Mobile with stick, and mobility scooter to pub Titrates Flucloxacillin against CRP, but generally 250mg nocte.

30 Alternative therapy delivery

31 77 year old man Peripheral vascular disease Large ischaemic ulcers Non healing Heavily colonised with coliforms and Pseudomonas aeruginosa.

32 32 yr old IDDM # Calcaneum. Infected metal work removed. Fluclox + honey and vac dressing Day 0 Day 14

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