1. MRSA (Methicillin Resistant Staph. aureus) Geog 380

2. GENERAL COMMENTS about resistance  Inevitable  “dance” of co-evolution  Post WW II—steadily growing  Widespread overuse  Use in cattlefeed

3. “The way to the wound is through the nose” --Creech II et al, 2006

7. Chronology of MRSA  First reported UK 1961  First reported USA 1968  Community associated MRSA (CA- MRSA) first reported 1980 –Initially US –Pts lack risk factors for MRSA

8. CA-MRSA Georaphically Dispersed (community acquired)  Australia--Aboriginals/native peoples  Native Americans in US--rural  Subpopulations in US –IDUs –Prisoners –Sports players –kids

11. Bilateral Necrotizing Fasciitis--Pseudomonas Source: Akamine et al, Internal Medicine 2008;47:553-6

12. Paradigms of CA-MRSA  It spread from hospital –Patients –Visitors –Staff  Current findings –It has been in reservoirs in community –The strain has been different than hospital MRSA –Some nosocomial MRSA is CA-MRSA!!!!

13. Sobering Quotes  “Community- associated…MRSA now appears to be among the most common etiologies of skin and soft tissue infections.”

14. “MRSA may be replacing methicillin-susceptible S. aureus (MSSA) as the typical community staphylococcal strain.”

15. “it is difficult to justify using drugs like cephalexin…if it is known that the majority of patients will be infected with resistant isolates.” See Moran and Talan, Annals of Emergency Medicine, 2004;11:321-22.

16. Prevalence of CA-MRSA  No national data collected  Community data difficult to get  Hospital data easier  Varies 76% of MRSA in AK to 12% MN for soft tissue infections  Huang et al, Journal of Clinical Microbiology 2006;44:2423-27

17. Hospital MRSA  Formerly: –Few large university hosps –ICUs  Now: –97% teaching hosps report MRSA  Risk factors: –Long hospital stay, surgery, catheter sites (prop to # of sites), long or recurrent exp to abx’s

18. Evidence of CA-MRSA Increase  10/100,000 admissions, kids, 1988-90  259/100,000 1993-5  See Herold et al, JAMA 1998;279:593-8  1993: 2,000 MRSA  2005: 368,000  APIC: 46/1000 hosp adm had life threatening MRSA  CDC: 94,000 life threatening hosp MRSA infs and 19,000 deaths!!!!  STAY HEALTHY

19. Frazee Study (Frazee et al, Annals of Emergency Med, 2005;45:31-20  Done in ER in Alameda County, CA  18% homeless, 28% IDU, 63% w abscess, 26% admitted to hosp  Nearly 50% patients w/ skin and soft tissue infections MRSA  74% of staph was MRSA  “When skin and soft tissue infections require antibiotic therapy, we recommend choosing an agent that is active against MRSA”

20. Findings of Huang et al  45% of pts w/MRSA had community associated MRSA  Not susceptible to usual abx’s for soft tissue infections but susceptible to: –TMP/SMX (Bactrim or Septra) –Gentamicin –Rifampin –Vancomicin –Clindamicin

21. Necrotizing Fasciitis  “flesh eating bacteria”  Fairly rate  Spectacular  Life-threatening  Surgical emergency  Polymicrobial –Toxin producing –Necrosis of fascia

22. Historical Background  Hippocrates 5th Cent BCE  19th C: –“gangrenous ulcer”, “malignant ulcer”, “putrid ulcer”, phagedema gangrenosa  1800’s –Feared in the military…  Confused by multiple terms@ present

23. Epidemiology  Estimated 500-150 cases/yr in US  Not specific by age or sex  Increased risk in: –IVDU –Alcoholics –Immunosuppressed –Peripheral vascular disease –diabetics

24. Typical Presentation  Any break in the skin  Increased risk w/trauma –Penetrating –Blunt –Surgical wound –IVDU –SC drug use –Perirectal abscesses –Bites –Da da da da

25. Clinical Presentation  Within 7 days of “injury”  Red, swollen, tender, hot, painful area  Pain out of proportion to physical findings  Pain extends beyond boundaries of erythematous area  Rapid, rapid expansion

26. CFR  Typically 75% –Sepsis –ARDS  Higher at Harborview

27. WARNING: SOME SLIDES AFTER THIS GET VERY GRAPHIC. NO KIDDING

28. Hsiao F and Hsieh C. N Engl J Med 2008;358:940 A 65-year-old woman with a 15-year history of diabetes presented with fever (temperature, 38.5{degrees}C), chills, malaise, and a rash on the medial surface of the right thigh, vulva, and lower abdominal wall (Panel A)

29. Necrotizing Fasciitis of Left Lower Leg Source: Kihiczak et al, JEADV

30. Nec Fasc of the Perineum

31. Infections and Layers Source: Chest 1996

32. NDM-1 New Delhi Metallo-beta- lactamase-1

33. HUH????  “What’d the dude say?”  “Sounded like he was barfing”  “I’m texting my girlfriend. How do you spell that?”  “Will it be on the test?”  “You mean this isn’t Philosophy 101”?

34. NDM-1  Not a specific bacterium  A genetically coded mechanism in gram negatives (klebsiella, etc), E. coli  Cleaves ring in carbapenems (carbapenamase)  Relatively new broad spectrum antibiotics including imipenem, meropenem

35. Why should we care?  Renders a major class of antibiotics useless  These antibiotics are frequently the only effective ones against enterobaceteriacae  Also many other pathogens  Few if any treatments then work

36. Lancet ID, April 7, 2011  “such pathogens typically are resistant to multiple other antibiotic classes, leaving very few treatment options available”

37. So let me explain  Enzyme is made by the bacterium based on instructions from its genome  This attacks the chemical structure of the “new” class of antibiotics  Cuts a ring  Neutralizes the antibiotic

38. Journal of Chinese Medical Association, Nov. 2010

39. NDM-1 in Water Supply, New Delhi Source: Lancet ID, 4-2011