1. Evidence-based Medicine

2. Case Presentation 27 yo AA male presents to clinic with 3 days of pain and swelling in right leg First noted several spider bites on his leg – concerned they may be infected now Denies fever, chills, nausea, or other symptoms

3. Case Presentation PMH: HTN Meds: HCTZ, Adalat Allergies: NKDA Social: AD PO2 on shore duty at NI. Lives in Chula Vista with his wife. No recent antibiotics or hospital contacts

4. PE Vitals: BP - 132/82 P - 64 T - 98.1 Gen: AAOX3, Appears well CV/Pulm: Unremarkable Right LE: Small, open pustule with surrounding edema, erythema. Scant thick, white discharge from lesion.

5. Diagnosis Uncomplicated cellulitis

6. Question What antibiotic is appropriate for uncomplicated cellulitis in an outpatient without risk factors for MRSA?

7. Choices… A) Any cephalosporin B) vancomycin C) linezolid D) TMP-SMX E) clindamycin F) a fluoroquinolone G) a tetracycline H) An antistaphylococcal PCN I) Combination therapy

8. What bug is targeted? a)MSSA b)Streptococcus c)MRSA d)Pseudomonas

9. Is MRSA a concern? Emergence of CA-MRSA USA300 Clone as the Predominant Cause of Skin and Soft-Tissue Infections King, et al. Annals of Internal Medicine, 7 March 2006.

10. Background CA-MRSA known to be pathogen in select populations (prisons, military recruits) Is this an important community pathogen?

11. Methods Prospective study at single public inner-city hospital (Atlanta, GA) over 3.5 months in 2003. Retrospective review of records for all pts with S. aureus culture for HIV status, ESRD, hospitalization within 12 months, hx of MRSA, and cx within 72 hours of admission Reviewer was blinded to type of S. aureus infection

12. Genetic Analysis Pulse-field gel electrophoresis on most samples – compared to CDC samples Assessed for Panton- Valentine leukocidin gene by PCR

14. Statistical Analysis Univariate analysis of potential risk factors in MRSA USA 300/400 vs MSSA and MRSA USA 300/400 vs MRSA other. Then multivariate analysis of potential risk factors

15. Univariate Results

16. Multivariate Results

17. Discussion 72% of all S. aureus infections were caused by MRSA USA 300/400 clone accounted for 87% of ca-MRSA infections

18. Author’s conclusions MRSA coverage is essential to empiric coverage of skin and soft tissue infections I&D alone may be sufficient, but poor data USA 300 clone is usually sensitive to TMP-SMX, linezolid, tetracycline May have inducible clindamycin resistance

19. Study Weakness Only examined culture positive S. aureus infections, not all soft tissue infections All data from one hospital No evaluation of treatment

20. Surviving the New Killer Bug From Time Magazine; 26 June 2006 “This is not bird flu or SARS or even the "flesh-eating bacteria" of tabloid fame. But it is every bit as dangerous, even if it goes by an uncommonly ungainly name: community-acquired methicillin-resistant Staphylococcus aureus (MRSA). Never heard of it? Neither have most doctors.”

22. CA-MRSA Typically USA 300 or USA 400 clone Normal resistance pattern includes resistance only to β-lactams and erythromycin Occasional resistance to levofloxacin, clindamycin, rifampin, and gentamycin Contains Panton-Valentine leukocidin gene (pvl) and SCCmec type IV gene

23. Panton-Valentine leukocidin gene Thought to be one of the major virulence factors for CA-MRSA Causes leukocyte destruction and tissue necrosis

24. Nosocomial MRSA Usually MDR Does not contain Panton-Valentine leukocidin gene

25. Is this applicable to our population? MRSA Infections among Patients in the Emergency Department Moran, et al. NEJM – 17 August 2006

26. Methods Prospective prevalence study Enrolled patients in 11 ERs with acute, purulent skin infections in August 2004 Isolates typed with PFGE and PCR

27. Results S. aureus isolated in 76% of patients MRSA isolated in 59% of patients (78% of S. aureus cultures)

28. Results

30. Discussion 97% of MRSA was a USA 300 strain Susceptibilities: 100% TMP-SMX and rifampin; 95% clindamycin; 92% tetracycline Infectious organism resistant to antibiotic prescribed in 57% of patients (most common antibiotic was a β-lactam)

31. Discussion 59% of patients contacted for follow-up 96% of these patients reported the infection resolved or improved No association between antibiotic used and outcome in limited follow-up

32. Discussion 99% of MRSA had PFGE consistent with CA-MRSA, although 25% had risk factors for health-care associated MRSA

33. Study Weakness Poor follow-up – study not designed for treatment arm Only included purulent infections Only enrolled 42% of eligible patients

34. Question? What antibiotic is appropriate for uncomplicated cellulitis in an outpatient without risk factors for MRSA?

36. My Thoughts Treatment of any abscess requires drainage first Culture should always be performed on purulent infections Antibiotic coverage must include, at minimum, coverage for MRSA, MSSA, and group A streptococcus

37. My Thoughts A) Any cephalosporin – Will miss MRSA B) vancomycin – Not appropriate for outpatient C) linezolid – Very expensive; may induce resistance D) TMP-SMX – Will likely miss streptococcus E) clindamycin – May miss MRSA (inducible resistance) F) A fluoroquinolone – Will miss MRSA, +/- vs strep G) A tetracycline – Good coverage if tolerated H) Antistaphylococcal PCN – Will miss MRSA I) Combination therapy – More difficult, less compliance

38. My Thoughts Combination of TMP-SMX plus β-lactam until sensitivity results are available is appropriate empiric coverage Single coverage with a tetracycline is also appropriate Clindamycin not recommended as single therapy unless a “D-test” is performed

39. My Patient No culture performed Treated with clindamycin with full resolution of symptoms

40. Questions?

41. Sources Fridkin, Scott, et al. MRSA Disease in Three Communities. NEJM 352;14 Graham, Philip, et al. A US Population-Based Survey of S. aureus Colonization. Annals of Internal Medicine. 7MAR2006; 144:318-325 Grayson, M. The Treatment Triangle for Staphylococcal Infections. NEJM; 355:724-726 King, Mark, et al. Emergence of CA-MRSA USA300 Clone as the Predominant Cause of Skin and Soft-Tissue Infections. Annals of Internal Medicine. 7MAR2006; 144:309-317 Moellering, Robert. The Growing Menace of CA-MRSA. Annals of Internal Medicine. 7MAR2006; 144:368-369 Moran, G.J, et al. MRSA Infections among Patients in the Emergency Department. NEJM 355;7 Pictures from: http://www.kcom.edu/faculty/chamberlain/