CA-MRSA: What You Need to Know

1. CA-MRSA:What You Need to Know Mahesh C. Patel, M.D. Internal Medicine-ID NBHN November 10, 2009

2. Need More Information? • http://www.cdc.gov/ncidod/dhqp/pdf/ar/CAMRSA_ExpMtgStrategies.pdf • Daum, RS. Skin and soft tissue infections caused by MRSA. NEJM 2007. 357:380-390. • Wallin, et al. Community-Associated MRSA. Emerg Med Clin N AM 2008. 26:431-455.

3. Community-Associated MRSA:CDC Population-Based Surveillance Definition • MRSA culture in outpatient setting or 1st 48 hours of hospitalization AND patient lacks risk factors for healthcare-associated MRSA: • Hospitalization • Surgery • Long-term care • Dialysis • Indwelling devices • History of MRSA www.cdc.gov

4. Microbiology • Methicillin resistance is mediated by the mecA gene (PBP2A) • mecA gene on SCCmec • HA-MRSA: SCCmec I-III • CA-MRSA: SCCmec IV-V • II and III carry resistance for non-beta lactams as well

5. Pathophysiology • PVL: Panton-Valentine Leukocidin • Exotoxin that is lethal to leukocytes • May be responsible for enhanced pathogenicity of CA-MRSA • NOT opportunistic

6. Clinical and molecular epidemiology of Staphylococcus aureus skin and soft-tissue infection King, M. D. et. al. Ann Intern Med 2006;144:309-317

7. Outbreaks of MRSA in the Community • Often first detected as clusters of abscesses or “spider bites” • Various settings • Sports participants • Inmates in correctional facilities • Military recruits • Daycare attendees • Native Americans / Alaskan Natives • Men who have sex with men • Tattoo recipients • Hurricane evacuees in shelters • HIV-infected individuals • African Americans • Pregnant and postpartum women Slide adapted from Gorwitz, R. CDC 2007.

8. Frequent Contact Crowding Defense Offense Cleanliness Antimicrobial Use Contaminated Surfaces and Shared Items Compromised Skin Factors that Facilitate Transmission Slide Courtesy of Gorwitz, R. CDC 2007.

9. CA-MRSA Infections are Mainly Skin Infections Disease Syndrome (%) Skin/soft tissue 1,266 (77%) Wound (Traumatic) 157 (10%) Urinary Tract Infection 64 (4%) Sinusitis 61 (4%) Bacteremia 43 (3%) Pneumonia 31 (2%) Slide Courtesy of Gorwitz, R. CDC 2007. Fridkin et al NEJM 2005;352:1436-44

10. Healthcare-Associated Community-Associated Most Invasive MRSA Infections Are Healthcare-Associated 86% 14% Slide Courtesy of Gorwitz, R. CDC 2007. Klevens et al JAMA 2007;298:1763-71

11. Incidence of Invasive CA-MRSA Infections and Deaths by AgeActive Bacterial Core surveillance (ABCS), 2005 Incidence per 100,000 persons Overall Incidence (all ages): Infections: 4.6 per 100,000 Deaths: 0.5 per 100,000 Slide Courtesy of Gorwitz, R. CDC 2007. Klevens et al JAMA 2007;298:1763-71

12. Black White Black White Incidence, Cases per 100,000 CA-MRSA Incidence Varies by Age and Race Atlanta, 2001-2002 Baltimore, 2002 26 per 100,000 18 per 100,000 Age Group (yr) Age Group (yr) Slide Courtesy of Gorwitz, R. CDC 2007. • Fridkin et al NEJM 2005;352:1436-44

13. MRSA Was the Most Commonly Identified Cause of Purulent SSTIs Among Adult ED Patients (EMERGEncy ID Net), August 2004 59% (97% USA300) 54% 39% 15% 55% 74% 51% 68% 60% 60% 72% 67% Slide Courtesy of Gorwitz, R. CDC 2007. Moran et al NEJM 2006;355:666-674

14. Clindamycin Resistance Among MRSA Isolates, Texas Children’s Hospital, Houston Texas,2001-2004 n=181 n=163 n=915 n=1192 n=198 n=551 Source: Hulten et al. PIDJ 2006;25:349-53, and Kaplan et al. Clin Infect Dis 2005;40:1785-91 Slide Courtesy of Gorwitz, R. CDC 2007.

15. Emerging Multi-Drug Resistance in USA300? • Clusters of USA300 isolates with multiple resistance to erythromycin, clindamycin, tetracycline, ciprofloxacin, and mupirocin1 • Resistance to ≤ one class of antibiotics other than beta-lactams is still the most common resistance pattern in MRSA USA300 • TMP/SMX resistance rare in MRSA USA300 1Diep et al Lancet 2006. Han et al J Clin Micro 2007. Slide Courtesy of Gorwitz, R. CDC 2007.

16. Strategies for Clinical Management of MRSA in the Community http:www.cdc.gov/ncidod/dhqp/ar_mrsa_ca.html

17. Clinical Considerations - Evaluation • MRSA belongs in the differential diagnosis of skin and soft tissue infections (SSTI’s) compatible with S. aureus infection: • Abscesses, pustular lesions, “boils” • “Spider bites” • Cellulitis? Slide Courtesy of Gorwitz, R. CDC 2007.

18. Clinical Considerations - Evaluation • MRSA should also be considered in differential diagnosis of severe disease compatible with S. aureus infection: • Osteomyelitis • Empyema • Necrotizing pneumonia • Septic arthritis • Endocarditis • Sepsis syndrome • Necrotizing fasciitis • Purpura fulminans Slide Courtesy of Gorwitz, R. CDC 2007.

19. Management of Skin Infections in the Era of CA-MRSA • I&D should be routine for purulent skin lesions • Obtain material for culture • Possible Exceptions: Uncomplicated abscess not needing rx; active CA-MRSA abx to be given immediately. • No data to suggest molecular typing or toxin-testing should guide management • Empiric antimicrobial therapy may be needed • Alternative agents have +’s and –’s: More data needed to identify optimal strategies • Use local data for treatment • Patient education is critical! • Maintain adequate follow-up Slide Courtesy of Gorwitz, R. CDC 2007.

20. Uncomplicated Abscess Data • No benefit with antibiotics in all prospective studies (4 total). • Rajendran, et al: • CA-MRSA cure • 84% cured with cephalexin vs. 90% in placebo group • >90% isolates were + for PVL genes Rajendran, et al. AAC. 2007; 51: 4044.

21. When to Use Antibiotics? • Complicated abscess (fever, lymphangitis, or surrounding cellulitis) • Rapidly progressive or severe local disease • Abscess > 5cm diameter • Comorbidities or immunosuppresion • Inability to completely drain abscess • Extremes of age • Failed prior I&D Wallin, et al. Emerg Med Clin North Amer. 2008; 26: 431.

22. Antimicrobial Susceptibility Patterns of Methicillin-Resistant Staphylococcus aureus Isolates according to Pulsed-Field Type King, M. D. et. al. Ann Intern Med 2006;144:309-317

23. Oral Agents for Outpatient Treatment of CA-MRSA Daum, RS. NEJM. 2007. 357:380.

24. Parenteral Agents for Inpatient Treatment of CA-MRSA Daum, RS. NEJM. 2007. 357:380.

25. Clinical Considerations - Management Antimicrobial Selection (SSTIs) • Alternative agents (More data needed to establish effectiveness!): • Clindamycin – Potential for inducible resistance, Relatively higher risk of C. difficile associated disease? • TMP/SMX – Group A strep isolates commonly resistant • Tetracyclines – Not recommended for <8yo • Rifampin – Not as a single agent • Linezolid – Expensive, Potential for resistance with inappropriate use Slide Courtesy of Gorwitz, R. CDC 2007.

26. Clinical Considerations - Management Antimicrobial Selection (SSTIs) • Not optimal for MRSA (High prevalence of resistance or potential for rapid development of resistance): • Macrolides • Fluoroquinolones Slide Courtesy of Gorwitz, R. CDC 2007.

27. D-zone test for Inducible Clindamycin Resistance E CC • Perform on erythromycin-resistant, clindamycin-susceptible S. aureus isolates • Clinical implications unclear, but treatment failures have occurred • Does not require pre-treatment or co-treatment with erythromycin in vivo Slide Courtesy of Gorwitz, R. CDC 2007.

28. MRSA: Clindamycin vs. TMP/SMX JACOBI NCB

29. Treatment algorithm for SSTIs Uncomplicated Abscess • Complicated Abscess • (significant cellulitis) • Immunocompromised • Infected wound, foot ulcer, etc. • Cellulitis • Impetigo • Consider surgical tx • Cover CA-MRSA and Group A Strep • Surgical Treatment • Strongly consider no abx • If abx used, cover CA-MRSA • Doxycyline or TMP/SMX alone • Cover Group A Strep • Cephalexin +/- • TMP/SMX • IV Therapy • Vancomycin + Clindamycin • Or • Vancomycin +Zosyn • (if Gram neg. suspected) • PO Therapy • Cephalexin + TMP/SMX • Or • Clindamycin alone Wallin, et al. Emerg Med Clin North Amer. 2008; 26: 431.

30. Linezolid vs. Vancomycin • Patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns (<10% of total body surface area). • ITT: 92.2% and 88.5% (Linezolid vs. Vanco.) • TOC: 88.6% vs. 66.9% • DAE were the same for both groups Weigelt J., et al. AAC. 2005; 49: 2260.

32. Other Infections • Pyomyositis • Bacteremia with seeding of damaged tissue. • S aureus 60+% • Surgical drainage with Vanco/clindamycin/linzeolid • Septic Arthritis/Osteomyelitis • May be more severe with CA-MRSA • Joint drainage and irrigation with iv abx (namely, vancomycin and clindamcyin) • Community-Acquired Pneumonia • CA-MRSA is rare (<2%); MSSA is more common • Influenza-like illnesses • Linezolid and/or clindamycin may be better than vancomycin

33. Management of Severe / Invasive Infections • Vancomycin remains a 1st-line therapy for severe infections possibly caused by MRSA • Other IV agents may be appropriate Consult an infectious disease specialist. • Final therapy decisions should be based on results of culture and susceptibility testing • Severe community-acquired pneumonia: Vancomycin or linezolid if MRSA is a consideration* *IDSA/ATS Guidelines for treatment of CAP in adults: Mandell et al. CID 2007;44:S27-72 Slide Courtesy of Gorwitz, R. CDC 2007.

34. Decolonization • Limited Data and no published trials • Consider in: • Multiple CA-MRSA SSTIs • Multiple household contacts are infected • Households with extremes of age, immunosuppressed members

35. Sample Decolonization Regimen • If nares screen is positive: • Intranasal mupirocin x5d AND • 2% chlorhexidine showers (2x/day) • If nares screen negative, but others are positive: • 2% chlorhexidine shower only • If all sites are negative: • No decolonization recommended Guidelines for Patients with Recurrent MRSA Skin Infections At Weiler Hospital. Courtesy of Chris Coyle, MD

36. Role of Pets • Greatest risk of Staph aureus / MRSA exposure in most humans is other humans • When household pet animals carry MRSA, likely acquired from a human • Transmission of MRSA from an infected or colonized pet to a human is possible, but likely accounts for a very small proportion of human infections • Reasonable to consider pet as a source if transmission continues in a household despite optimizing other control strategies • Little evidence that antimicrobial-based eradication therapy is effective in pets; however, colonization tends to be short-term* Slide Courtesy of Gorwitz, R. CDC 2007. Barton et al 2006;Can J Infect Dis Med Microbiol

37. Preventing Transmission • Exclusion of patients from school, work, sports activities, etc should be reserved for those that are unable to keep the infected skin covered with a clean, dry bandage and maintain good personal hygiene. • In general, it is not necessary to close schools to “disinfect” them when MRSA infections occur. • In ambulatory care settings, use standard precautions for all patients (hand hygiene before and after contact, barriers such as gloves, gowns as appropriate for contact with wound drainage and other body fluids). www.cdc.gov

38. Preventing Transmission • Persons with skin infections should keep wounds covered, wash hands frequently (always after touching infected skin or changing dressings), dispose of used bandages in trash, avoid sharing personal items. • Uninfected persons can minimize risk of infection by keeping cuts and scrapes clean and covered, avoiding contact with other persons’ infected skin, washing hands frequently, avoiding sharing personal items. www.cdc.gov

39. http://www.princetoncme.com/public/2006-151/report2.php

40. http://www.princetoncme.com/public/2006-151/report2.php

41. http://www.princetoncme.com/public/2006-151/report2.php

42. http://www.princetoncme.com/public/2006-151/report2.php

43. http://www.princetoncme.com/public/2006-151/report2.php

44. http://www.princetoncme.com/public/2006-151/report2.php

45. Antimicrobials In Development • Glycopeptides • Dalbavancin • Oritavancin • Telavancin • Cephalosporins • Ceftobiprole

46. Need More Information? • http://www.cdc.gov/ncidod/dhqp/pdf/ar/CAMRSA_ExpMtgStrategies.pdf • Daum, RS. Skin and soft tissue infections caused by MRSA. NEJM 2007. 357:380-390. • Wallin, et al. Community-Associated MRSA. Emerg Med Clin N AM 2008. 26:431-455.