1. Zartash Khan, MD 11/12/11 MRSA AND VRE

2. Incidence Spectrum of disease Treatment Decolonization Resistance mechanism Spectrum of disease Treatment Resistance MRSAVRE OVERVIEW

3. STAPHYLOCOCCUS AUREUS Sir Alexander Ogston,Staphylococci: Greek- staphyle- "bunch of grapes".Staphylococci: Greek- staphyle- "bunch of grapes". Aureus: : Latin – “gold”

4. 20 year old M presented to ER for a right forearm abscess I&D and home with Bactrim A week later presented again with fevers (temp 103’), abdominal pain, constipation and urinary retention WBC 22K Admitted to surgery and started on Cipro and Flagyl L spine MRI CASE PRESENTATION

5. Blood cultures 2/2 grew S. aureus Neck stiffness, LP ordered, started on Vanc 1 gm q 12’, ID consulted Exam: neck stiffness, significant back pain, foley in place, neuro intact but limited exam Vanc increased to 1.5 gm q 8 hrs MRI spine, LP held CASE PRESENTATION

10. HA-MRSA USA-100 & 200 Panton-Valentine Leukocidin absent Bacteremia, Osteo Resistant to most antibiotics CA-MRSA USA-300 & 400 Pvl present SSI Susceptible to non beta lactam MRSA IN THE US

12. Additional cost per MRSA infection ~ $10,000 Total cost of MRSA infections per year ~ $8 billion Average length of stay: 6 extra hospital days Number of MRSA infection deaths per year: 20,000 to 40,000 MRSA INFECTION, U.S. STATISTICS MRSA Infection Statistics; March 23, 2009

13. 2007 Incidence 31.8/100,000 Klevens et al. JAMA 2007;298 >94,000 cases of invasive disease reported in 2005 MMWR report From year 2005 through 2008 HA-MRSA infections declined 28% Invasive HA-community onset MRSA infections declined 17% INCIDENCE

14. National Estimates of Invasive MRSA Disease Cases: 89,785 (29.53/100,000) Deaths: 15,249 (5.02/100,000) INCIDENCE CDC. 2008. Active Bacterial Core Surveillance Report, Emerging Infections Program Network MRSA, 2008.

15. Data from 600 nationwide ICUs Out of 21,503 episodes of invasive MRSA infection identified from 2005 - 2008 17,508 were healthcare-associated infections; Including 15,458 MRSA BSIs INCIDENCE JAMA. 2010;304:641-648, 687-689

17. Skin and soft-tissue infections Bacteremia and endocarditis Pneumonia Bone and joint infections Central nervous system disease Toxic shock and sepsis syndromes SPECTRUM OF DISEASE

18. SSI

21. Options for treating both β -hemolytic streptococci and community-associated MRSA include; Clindamycin alone TMP/SMX or a tetracycline in combination with a beta-lactam antibiotic (e.g., amoxicillin) or linezolid alone SSI TREATMENT Clinical Infectious Diseases2011;1–38

22. Hospitalized patients empiric therapy options include: Intravenous vancomycin Linezolid Daptomycin Telavancin or Clindamycin A beta-lactam antibiotic (e.g., cefazolin) may be considered in hospitalized patients with nonpurulent cellulitis. SSI TREATMENT Clinical Infectious Diseases2011;1–38

23. Ceftaroline Tigecycline SSI TREATMENT

24. Uncomplicated bacteremia: defined as patients with positive blood culture results and the following: exclusion of endocarditis no implanted prostheses follow-up blood cultures performed on specimens obtained 2– 4 days after the initial set that do not grow MRSA defervescence within 72 h of initiating effective therapy no evidence of metastatic sites of infection BACTEREMIA

25. Uncomplicated: Vancomycin or daptomycin for at least 2 weeks Complicated: 4–6 weeks of therapy is recommended *variable BACTEREMIA TREATMENT Clinical Infectious Diseases2011;1–38

26. Only 15-20 % success rate if CVC retained Risk of prosthetic valve endocarditis ~43% 1 Similar rates with vascular grafts, pace makers etc Persistent fever and/or bacteremia >3 days associated with increased risk of complications Incidence of native valve endocarditis 25% 3 CAVEATS RELATING TO S. AUREUS BACTEREMIA 1.Fang et al. Ann Intern Med,1993 2.Ekkelenkamp et al. CID 2008 3.Fowler et al. JACC 1997

27. CHEST CT OF A PATIENT WITH NECROTIZING PNEUMONIA CAUSED BY CA-MRSA USA300 GENOTYPE. THE CT SCAN, OBTAINED ON HOSPITAL DAY 5, SHOWS MULTIPLE NODULAR LESIONS, SOME WITH A CENTRAL CAVITATION, AND BILATERAL PLEURAL EFFUSION. VALENTINI ET AL. ANNALS OF CLINICAL MICROBIOLOGY AND ANTIMICROBIALS 2008 7:11

28. Hospitalized patients with severe community-acquired pneumonia defined by any one of the following: Requirement for ICU admission, Necrotizing or cavitary infiltrates, or empyema, Empirical therapy for MRSA is recommended pending sputum and/or blood culture results PNEUMONIA

29. IV vancomycin Linezolid Clindamycin if sensitive Duration 7-21 days Fluoroquinolones may have activity against some CA- MRSA isolates, but they are not routinely recommended PNEUMONIA TREATMENT Clinical Infectious Diseases2011;1–38

30. IV vancomycin daptomycin clindamycin Linezolid TMP/SMX +/- rifampin BONE AND JOINT INFECTION Clinical Infectious Diseases2011;1–38

31. MRI of the brain of a patient with abscesses caused by infection due to USA300 methicillin- resistant Staphylococcus aureus. Sifri C D et al. Clin Infect Dis. 2007;45:e113-e117 © 2007 by the Infectious Diseases Society of America

32. Meningitis, abscess, Cavernous phlebitis, device infection Treatment: Vancomycin Linezolid TMP/SMX CNS INFECTIONS:

34. Results from a prospective cohort study from January 2002 to April 2007 Most frequent locations of MRSA colonization were: nose (68%] throat (53%) perianal area (53%) rectum (58%) inguinal area (49%) DECOLONIZATION Infect Control Hosp Epidemiol. 2008 Jun;29(6):510-

35. Nasal decolonization with mupirocin twice per day for five to 10 days Or nasal decolonization with mupirocin twice per day for five to 10 days plus topical body decolonization with a skin antiseptic solution (e.g., chlorhexidine [Peridex]) for five to 14 days or dilute bleach baths Oral antimicrobial therapy is recommended only for treating active infection and is not routinely recommended for decolonization DECOLONIZATION

36. Success? Meta-analysis of 23 studies (1977-2008), 2114 subjects BID mupirocin intranasal for 4-7 days ~90% clearance at 1week ~60% longer-term clearance(2weeks to 1year) Recurrence Incomplete clearance, extranasal sites, co-morbidities, resistance, recolonization DECOLONIZATION Ammerlaan et al., Clin Infect Dis, 2009

37. Penicillinase ANTIBIOTIC RESISTANCE IN S. AUREUS FOLLOWING DISCOVERY OF PENICILLIN

38. BRIEF TIMELINE USA300 MRSA clone first surfaced in the year 2000 in the United States and rapidly underwent clonal expansion In 2002 VRSA- reported in USA

39. 1940's

41. Enright MC, Robinson DA, Randle G, Feil EJ, Grundmann H, Spratt BG. The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc Natl Acad Sci U S A. 2002;99:7687-92 RESISTANCE

42. Treatment of bloodstream infections caused by MRSA strains having a vancomycin MIC of ≤0.5 mg/L had an overall success rate of 55.6% While treatment of patients infected with MRSA strains having a vancomycin MIC of 1–2 mg/L had a success rate of only 9.5% (p = 0.03). MIC CREEP J Clin Microbiol. 2004; 42:2398-402.

45. Bacteremic for 5 days Vanc trough < 10 despite 1.25 gm q 6hrs Switched to daptomycin 8mg/kg q 24’ 2D echocardiogram negative CASE FOLLOW UP

47. E. faecalis E. faecium VANCOMYCIN RESISTANT ENTEROCOCCUS

48. Urinary tract Biliary tract Blood (i.e., bacteremia, sepsis) Respiratory tract (i.e., pneumonia)pneumonia) Heart infections Central nervous system (i.e., meningitis) SPECTRUM OF DISEASE

49. Five types of Vancomycin (glycopeptide) resistance (VanA, VanB, VanC, VanD, and VanE) all externally acquired except for VanC which is a chromosomally encoded characteristic of the species RESISTANCE

51. Linezolid Daptomycin Quinopristin/dalfopristin (not E. faecalis) Tigecycline Ampicillin (if susceptible) VRE TREATMENT

52. THANK YOU