Treating skin and soft tissue and bone and joint infections in acute and OPAT settings

1. Treating skin and soft tissue and bone and joint infections in acute and OPAT settings Andrew Seaton Infectious Diseases Consultant and Lead Doctor Antimicrobial Management Team, Brownlee Centre Gartnavel General Hospital NES Training Day to support Antimicrobial Pharmacists Friday 30 August 2013

2. Cellulitis Cellulitis vs Erysipelas Risk factors: Previous cellulitis, lymphoedema, DM, Obesity, varicose excema, insect bites (summer), tinea pedis…. Usually caused by: Beta haemolytic Streptococci Gp A>> Gps B, C, G Staphylcoccous aureus Rarely Gram negatives (immunocompromised)

3. Cellulitis: First line antibiotic management Flucloxacillin (vs MSSA, BHS (most)) Oral 7 days if mild IV-IVOST if moderately severe 7-10 days total IVOST when significant reduction in heat, erythema and swelling Should Ben Pen be added? Penicillin allergic Clarithromycin or Clindamycin (PO) Vancomycin (IV)

4. How is severity assessed? • Extent, speed of progression and presence of systemic inflammatory response

5. Abrupt onset fever, rigors and confusion ++ • Rapidly progressive Cellulitis of leg • BP 80 systolic, HR 140,Temp 39.80C

6. Abrupt onset fever, rigors and confusion ++ • Rapidly progressive Cellulitis of leg • BP 80 systolic, HR 140,Temp 39.80C

7. Severe GAS Sepsis • “Eagle effect” • Static growth phase • Failure to produce PBPs • Exotoxin: STSP

8. 28 day Mortality & Sepsis SeverityPatients suspected of bacteraemia Jones & Lowes, QJM 1996

9. Mortality Risk and time to initiation of effective therapy

10. Necrotising Fasciitis Usually caused by: Beta haemolytic Streptococci Gp A>> Gps B, C, G Staphylcoccous aureus Rarely Gram negative organisms Pain out with appearance Masked by NSAIDs Rapidly progressive with multiorgan failure

11. Management of severe/ rapidly progressive SSTIs SEPSIS 6, Fluid resuscitation and inotropes HDU setting Antibiotic considerations: Cover: BHS, Anaerobes, Staph aureus and Gram –ves Cidality: Beta lactam based regimen Toxin production/ EAGLE effect: Clindamycin Immunoglobulin (GAS) SURGERY

12. MRSA carrier. not getting better on VANCOMYCIN Why not?

13. Surgical Site Infections

14. Diabetic with forefoot cellulitis Not getting better on FLUCLOXACILLIN Why not?

15. Drug users: MSSA and GAS most usually Cellulitis, deep SSTIs, Abscesses, Vascular infections, DVTs and bacteraemia

16. OPAT and SSTIs

17. OPAT Evidence in SSTI • 2 RCTs of OPAT: 1999 (n=100, variety) and 2004 (n=200, SSTI). • Mainly Cefazolin BD • RCTs of new antimicrobials includes OPAT Rx pts Corwin et al BMJ doi 10.1136/bmj.38309.447975.EB; Board et al Aust N Z J Public Health 2000; 24:305

18. When to consider OPAT • Non-life-threatening SSTI amenable for home care and requiring i.v. therapy • Admission avoidance or early discharge • Exclusions: • The system • Lack of facility/ system for FU/ emergency cover • The infection • Sepsis syndrome • Rapidly progressive/ progression not clear • The patient • Unstable co-morbidity • Psycho-social

20. Good Practice Recommendations 4.1 Patients with superficial skin and soft tissue infection should be reviewed daily by the OPAT team to optimize speed of intravenous to oral switch.

21. Patient group direction for SSTIs ‘Patient group’: non-life-threatening cellulitis amenable for home care and requiring i.v. therapy Uniform therapeutic management Suitable protocol in place Exclusions Prior physician review Indications for specialist review Indications for IVOST Trained, experienced staff Approved by ADTC IVOST, i.v. antibiotic – oral switch therapy Seaton RA et al. J Antimicrob Chemother 2005;55:764–767

22. OPAT treatment pathway for SSTIs: empiric antibiotic choice History of MRSA or Beta-lactam allergy? Yes No Ceftriaxone ▼Clindamycin or Flucloxacillin Teicoplanin ▼ Clindamycin* *If Beta-lactam allergy or sensitive MRSA

23. Nurse-led Mx for OPAT SSTIs Comparison of patients pre- and post-introduction of a nurse-led management protocol • Protocol management was associated with reduced duration of outpatient i.v. therapy (from 4 to 3 days, P=0.02) Seaton RA et al. J Antimicrob Chemother 2005;55:764–767

24. SSTI: Median duration of OPAT (days) Nurse-led IVOST Linear time trend in log (OPAT days) Estmate 0.904 (0.886-0.922) p<0.0001 Seaton RA et al, IJAA, 2011

25. Common OPAT Antibiotics in SSTI *Switch of antibiotic, progression of infection or readmission Seaton RA et al, IJAA 2011

26. Factors Associated with OPAT Failure* in SSTI (n=963) *Switch of antibiotic, progression of infection or readmission Seaton RA et al, IJAA 2011

27. OPAT SSTI: Factors Associated with increase in duration of OPAT * Estimates: percentage change in number of days in OPAT: for example, an estimate of 1.10 means that, on average, a variable is associated with a 10% increase in the number of days of treatment. Seaton RA et al, IJAA 2011

28. OPAT SSTI: Antibiotic therapy • Nurse led IVOST effective and associated with reduced duration of IV Rx • OPAT failure and Teicoplanin • confounded by another variable? • Teicoplanin less effective / more adverse events? • Less subject to daily IVOST review therefore longer therapy? • Alternative therapies when ceftriaxone contraindicated

29. 65 yr old female diabetic Bilateral amputee with recent admission with ?UTI Readmitted 2/52 post discharge with fever, fatigue, headache and confusion Temp 39 HR 120 BP 134/90 WCC 16 Urinalysis; glycosuria

30. GAS, Pneumococcus, Meningococcus, other Strep sp MSSA Gram negs

31. Gram positive cocci on blood culture @ 24 hours

32. Continue empirical Rx until confirmed and assuming clinical repsonse S. aureus confirmed (MSSA) Where is it coming from and what are the dangers?

33. Bone and joint Infection

34. Bone and joint Infection • Diversity of presentations • Managed by many specialties • About 1m Implants/annum world wide • 0.5% of THR • 0.5-2% of other PJs • BJI in Glasgow; >500 per year

35. OM due to contiguous spread Eg Trauma, Surgery or joint replacement OM due to vascular insufficieny Eg Following Soft tissue infection in a diabetic (associated neuropathy) Haematogenous OM EgDiscitis Onset Acute; Days – weeks Chronic; Months - years Classification of Osteomyelitis Lew and Waldvogel, Lancet 2004; 364369

37. Likely Organisms • Device related • Coagulase negative Staphylococci > Staph aureus > Enterococci (sub-acute) • Staph aureus, BHS, Gram negatives (acute) • Non device related • Staph aureus, BHS • Gram negatives

38. How do bugs get in? • Through the skin or wound • Health care workers • Environment • From the Blood stream • Community • Cannulae / Catheters • Via surgery • Asepsis • Foreign material

39. Mechanism of disease:The bone • Acute suppurative inflammation • Micro-organism embedded • Tissue necrosis and destruction of bone trabeculae and matrix • Vascular channels compressed and obliterated

41. Pathogenesis: Host and micro-organisms • Staphylococcus aureus • Most common and important • Virulence through extracellular and cell-associated factors: • Attachment: Adhesins allow attachment to extracellular matrix proteins • Evading the host defence; Protein A, some toxins, capsular polysaccharide • Promote invasion or tissue penetration: Exotoxins and hydrolases

42. Pathogenesis: Host and micro-organisms • Staphylococcal species • Capacity to colonise and persist • Promote own uptake by endothelial and endocytic cells and can survive within osteoblasts • Can exist in metabolically altered status as small colony variants

43. Pathogenesis: Host and micro-organisms • Staphylococcal species • May persist in biofilm (“Slime”) • Cells attach to each other and substratum or interface • Matrix of extracellular polymeric substance • Altered growth, gene expression and protein production • Quorum sensing between organisms • Inherent resistance to antimicrobials • Metabolic alteration • Reduced cell division • “Layered variation” in phenotype

44. BJI Management • Microbiological Dx is essential • Imaging: Xray, CT, MRI, Bone scan • Acute Presentation • Blood cultures / joint aspiration • Management of sepsis: empirical therapy • Identify and remove foci of infection • Sub-acute presentation • Sample off antibiotics • Empirical Rx after sampling

45. Principles of antibiotic management • Combined with surgical management • Deliver to site of infection (bone/joint penetration) • Activity in biofilm • Route of administration: IV (by convention not evidence) initial and consider IVOST • Length of Rx: ≥6 weeks BUT dependent on surgical management • Cure vs Suppression • Maintenance of function

46. Choice of Antibiotic • Best guess: Glycopeptidevs flucloxacillin • Favour Flucloxacillin with Gentamicin if acute presentation • Consider 2nd oral agent Rifampicin>Sodium fusidate/ Doxycycline/ TMP/ Pristinamycin • Gram negative cover: Ciprofloxacin

47. OPAT

48. When to consider OPAT • When (prolonged) IV Rx anticipated • Ambulant / well supported patient • Stable comorbidity • Agreed plan between surgical team and OPAT • Clear lines of communication • No logistic obstacles • Usually self/ carer administration

49. Distribution of patients within the Glasgow OPAT service (2001-2011) a. OPAT patient episodes b. OPAT days Seaton and Barr, EJIM, 2013

50. Good Practice Recommendations 3.2 The treatment plan is the responsibility of the OPAT infection specialist, following discussion with the referring clinician. It should include choice and dose, frequency and duration. Should take into account flexibility based on clinical response 3.3 Antimicrobial choice within OPAT should be subject to review by the local antimicrobial stewardship programme