IDSA Clinical Practice Guidelines for the Treatment of MRSA

1. IDSA Clinical Practice Guidelines for the Treatment of MRSA R. Dinny Weber, M.D. 6/30/11

2. R. Dinny Weber, M.D. • Financial Disclosure • 6/28/2011 • neither I, nor any member of my immediate family, within the last 12 months, have had a financial relationship with any proprietary entity producing health care goods or services.

3. Prevention has obvious advantages • No pt has to endure the risk and suffering of infection (and treatment) • Prevention eases the pressure on antibiotics • Cost • Prevention just isn’t as sexy

4. Management of Skin and Soft Tissue Infections • MRSA now is frequently community-acquired • This has led to a dramatic increase in ER visits and admissions for SSTI s • One study found 25.9% of outpt. S. aureus was MRSA (Am. J Infect Control 2003;53) • 74% since 2001 at a Houston pediatric hospital

5. Cutaneous Abscess • Incision and Drainage is the cornerstone of treatment. • Cure rate is 85-90% • Value of antibiotics is less clear…in one study anitibiotic choice did not change outcome. • In two studies (adult and peds) TMS and Placebo were equivalent • Two other studies suggested benefit of ABX

6. Cutaneous Abscesses • Moist heat facilitates drainage and may be adequate for small furuncles • Impetigo and secondarily infected lesions may respond to topical mupirocin 2%

7. When to use Abx with I & D • Severe or extensive dz • Rapid progression with associated cellulitis • Comorbidities • Tough to drain • Lack of response to I & D alone • TOXICITY of the pt

8. Cellulitis • Not all red skin is cellulitis • Purulent? ( i.e. purulent drainage or exudate) • Treat empirically for MRSA. May not need to cover strep • Non-purulent? Cover strep. Add MRSA coverage if no response (timing?) or toxic

9. Purulent Cellulitis • Pts in 11 US EDs: 59% MRSA, 17% MSSA & 2.6% Beta strep

10. Non-Purulent Cellulitis • Hard to define etiology • Pre- CA-MRSA era Beta strep and MSSA • Only one prospective study of non-culturable cellulitis in inpts. Beta strep were responsible for 73% ( by serologic tests). 27% not ID’d • Clinical response to Beta lactam rx 96%

11. Oral Antibiotic Regimens for SSTI • Clindamycin (69% of local MRSA is sensitive) • TMS • TCN • Linezolid • Add Beta lactam to cover strep if TMS or TCN • Rifampin not recommended

12. Parenteral Regimens for SSTI - adults • Use for sicker patients…not always hopitalized • Vancomycin • Linezolid • Daptomycin • Telavancin • Clindamycin • Ceftaroline

13. Management of Recurrent MRSA SSTI • Personal hygiene and wound care • Avoid sharing personal items • Consider cleaning high-touch surfaces with commercially available cleaners

14. When to Decolonize • Recurrent SSTI despite optimal hygiene • Ongoing transmission in close contacts

15. Decolonization Strategies • Nasal mupirocin 2% BID for 5-10 days • Chlorhexidine baths or wipes for 5-14 days • Dilute bleach baths (1 tsp per gallon or ¼ cup per ¼ tub) for 15 mins. twice a week for 3 mos. • Consider oral abx if this fails • If interpersonal transmission suspected eval and rx contacts

16. When to culture • If sick or not responding or treated with abx or suspected cluster. • Not for surveillance or post-treatment f/u

17. MRSA Bacteremia • High morbidity and mortality (37% in SBE) • Must first decide if it is complicated or not.

18. Uncomplicated Bacteremia • Positive blood cultures • SBE excluded • No implanted prostheses • Negative follow up blood cultures at 2-4 days • Defervescence with in 72 hr. of effective rx • No metastatic foci • Use vancomycin or daptomycin (6mg/kg) for at least 14 days

19. Complicated Bacteremia • Positive blood cultures but don’t meet criteria for uncomplicated • Treat 4-6 wks with vanco or dapto (?8-10 mg/kg) • If SBE treat 6 wks • Do not add gent or rifampin to vanc for bacteremia or native valve SBE

20. Complicated Bacteremia • Look for source, other sites, debridable? • Follow up blood cultures • Echo heart (TEE preferred)

21. SBE – Native Valve Consider replacement if: Veg is > 10 mm 1 embolic event in 1st 2 week Valve failure CHF Abscess Persistent bacteremia or fever

22. SBE – Prosthetic Valve • Vanc plus rifampin (300 mg tid) for at least 6 weeks plus gent (1 mg/kg/dose q 8) for 2 weeks • Early evaluation for valve replacement

23. MRSA Pneumonia • For Severe community acquired pneumonia* empiric treatment should include MRSA coverage. *ICU, Cavities, empyema • For Healthcare associated pneumonia or documented MRSA Vanco or Linezolid or Clinda (if susceptible) for 7-21 days. • Daptomycin is not useful as it is inactivated by pulmonary surfactant

24. MRSA Osteomyelitis • MRI is imaging modality of choice • Surgical debridement is the mainstay of therapy • Abx. options: Vancomycin Daptomycin TMS (4mg/kg of trimeth BID) + Rifampin 600/d Linezolid Clindamycin

25. Duration of Therapy • Optimal duration is unknown • Minimum of 8 weeks (some say 1-3 mos more of oral rifampin with TMS, doxy, clinda, or FQ

26. Septic Joint - Native • Drainage or debidement of joint space should always be performed • Same abx. as for osteo • Treat 3-4 wks.

27. Device-Related Osteoarticular Infections • Early onset (< 2 mos. Post op or acute hematogenous seeding) AND • Stable implant AND • < 3 wks of sxs: initiate parenteral abx (like osteo) PLUS rifampin 600mg daily • Treat 2 wks iv then 3-6 mos po? • For spinal implants…treat until fused

28. MRSA – Bone and JointAdditional Considerations • Individual patient circumstances matter • Failure rates with vanco may be 35-40% • If pts have concurrent bacteremia, add rifampin only after clearance of the bacteremia.

29. Vancomycin Dosing • MIC “creep” has led to changes • 15-20 mg/kg (actual body wt.) q 12 h if nl renal fxn. (not more than 2 gm/dose) • If very ill consider loading dose of 25-30 mg/kg • Monitor troughs…shoot for 15-20

30. How to factor in the MIC • If MIC < 2 pt’s clinical response should determine whether vanco is continued • If pt has not had clinical or microbiologic response then change therapy whatever MIC is. (high dose daptomycin @ 10 mg/kg/day plus a second agent such as gent, rif, linezolid, TMS, beta-lactam) Also consider telavancin. • We have seen dapto resistance emerge on rx.

31. Antibiotic Notes • Vancomycin: Kills slower than Beta-lactams Clearly inferior to Beta-lactams for MSSA Variable tissue penetration High failure rate with MIC > 1 (CID 2011: 52 p969-974 and p975-981)

32. Antibiotic Notes - Daptomycin • Breakpoint <= 1 • Prior exposure to vanco and higher vanco mic’s associated with higher dapto mic’s • CPK may elevate…dose-related • Eosinophilic pneumonia

33. Antibiotic Notes - Telavancin • Bactericidal vs. MRSA, VISA, VRSA • May be more nephrotoxic than Vanco • No levels • Follow creatinine

34. Antibiotic Notes - Tigecycline • Not included in guidelines due to an FDA warning indicating higher all-cause mortality in patients treated with tigecycline vs comparator drugs.

35. Antibiotic Notes - Ceftaroline • New cephalosporin with activity vs MRSA • Has aerobic GNB activity about like ceftriaxone (ie no pseudomonas coverage) • BID dosing • Niche to be defined (? Lung data) • Role in SSTI unclear since no advantage over vancomycin

36. Mupirocin • Cochrane report: reduced nosocomial S. aureus infections. Mostly those undergoing surgery or dialysis. • One small study showed decreased MSSA recurrences • Resistance is a concern