1. Staphylococcal Bacteremia and Endocarditis: Epidemiological Considerations March 6, 2006 John Edwards, Jr., M.D Professor of Medicine UCLA School of Medicine Chief, Infectious Disease Department of Medicine Harbor-UCLA Medical Center

2. Increased Incidence of Sepsis in General Martin GS et al. N Engl J Med. 2003;348:1546-1554.

3. Increasing Incidence of Gram-Positive Sepsis No. of Cases of Sepsis 225,000 75,000 150,000 25,000 15,000 10,000 5,000 0 19791981198319971999200119951985 1987 19891991 1993 Gram-positive bacteria Fungi Gram-negative bacteria Martin GS et al. N Engl J Med. 2003;348:1546-1554.

4. Expanding Community Reservoir of MRSA Carleton et al. J Infect Dis 2004; 190: 1730-8. P=.0001 for trend Changes in MRSA transmissionChanges in MRSA genotype

5. Increase in Resistant Nosocomial MRSA ICU Patients Non-ICU Patients % Resistant Isolates NNIS. Available at: www.cdc.gov/ncidod/hip/NNIS. Accessed July 8, 2003.

6. Hageman, JC et al. IDSA 2004 abst #1148 CA-MRSA in US is Clinically Distinct: Severe Secondary Pneumonia >6000 US patients with Influenza in 2003-04 263 ID MDs across US in Emerging Infection Network

7. 116 Consecutive MRSA bloodstream isolates from Grady Hospital over 7 months available for genotyping MRSA USA300 - 28% Healthcare-associated BSI - 20% Nosocomial BSI MRSA USA300 - Injection drug use (3.67; 95%CI:1.10-12.28) - Skin & Soft Tissue (4.26:95%CI:1.08-16.8)

8. Necrotizing Fasciitis Caused by CA-MRSA Miller New Engl J Med 2005;352:1445-53 14 patients at Harbor-UCLA IDU: 50% Homeless: 21% Previous MRSA infection: 21% Bacteremia: 28% ST-8, USA 300 clone present in 100% Distinct virulence repertoire: pvl, sdrC-E, icaA, aroE,  hemolysin

9. CA-MRSA in US: Conclusions Now common community pathogen in many parts of US Clinically distinct: severe sepsis, necrotizing pneumonia, empyema, musculoskeletal infections, necrotizing fasciitis Genotypically distinct: SCCmecIV, pvl, seh Hospital and community MRSA intermingling

10. International Collaboration On Endocarditis (ICE)

11. International Collaboration on Endocarditis Merged Data Base

12. ICE Structure  58 Sites / 26 Countries Argentina (2) Australia (8) Brazil (2) Chile (2) Croatia (1) Denmark (1) England (2) France (4) Germany (2) Lebanon (1) India (2) Ireland (1) Israel (1) Italy (3) Lebanon (1) The Netherlands (1) New Zealand (1) Romania (1) Russia (2) Singapore (2) Slovenia (1) South Africa (1) Spain (5) Sweden (1) Thailand (1) United States (10)

13. Increasing Frequency of S. aureus IE International Collaboration on Endocarditis (ICE) ~ 1700 Prospective IE Cases from 20 Countries Fowler VG et al. JAMA. 2005;293:3012-3021.

14. Results 48-month study period 1779 patients with definite IE from 16 countries enrolled in ICE Bloodstream isolates simultaneously collected

15. Causes of 1779 Cases of Endocarditis by Region Fowler VG et al. JAMA. 2005;293:3012-3021.

16. Increasing Frequency of S. aureus IE: Evidence from > 2000 Patients from 5 Countries Miro JM et al. Clin Infect Dis. 2005;41:507-514.

17. Mortality in Patients with S. aureus IE P < 0.0001 Fowler VG et al. JAMA. 2005;293:3012-3021.

18. P < 0.001 (for trend) Cabell CH. Am Heart J. 2004;147:582-586. Increasing Rates of Cardiac Device Infections in Medicare Beneficiaries: 1990-1999

19. Increasing Numbers of Cardiac Devices Jauhar S. N Engl J Med. 2004;351:2542-2544.

20. S. aureus Bacteremia and Prosthetic Devices: Cost Chu V et al. Am J Med. 2005;118: 1416.e19-24.

21. CA-MRSA: An Emerging Cause of IE? Fowler, JAMA, 2005

22. S. aureus with Reduced Susceptibility to Vancomycin Vancomycin Resistant S. aureus: (VRSA) MIC> 32 µg/mL Vancomycin Intermediate S. aureus (VISA) MIC: 8-16 µg/mL Heteroresistant S. aureus (heteroVISA) MIC 8-16µg/mL Vancomycin “Failures” Cosgrove, SE. Clin Infect Dis 2004;39:539-45.

23. MMWR 2004; 53:322-3 Vancomycin Resistant S. aureus

24. General Summary Points: Epidemiology Increased Incidence of Bacteremias in General Increased Incidence of Gram Positive Bacteremias Substantial Increase in Bacteremia Due To Staphylococcus Staphlococcus aureus Is Now the Most Common Cause of Endocarditis The Increase in Staphylococcal Endocardits is Associated with Modern Health Care Advances There is a Highly Significant Increase in both Community and Nosocomial Sources of MRSA Internationally There is a Developing Increase in Staphylococcal resistance to vancomycin