1. Staphylococcal Infections Among Injection Drug Users Frederick L. Altice, M.D. Professor of Medicine Yale University School of Medicine

2. Background ~13 million IDUs estimated worldwide 1 Skin and soft tissue infections are the leading cause for ER visits and hospitalizations for IDUs (S aureus & S pyogenes most common pathogens) 2 S aureus nasal carriage occurs in ~20% of people and associated with development of community- and nosocomial-acquired S aureus infections 3,4 IDUs have a higher rate of S aureus colonization than the general population 3,5 S aureus nasal carriage has been associated with  development of subsequent infections in IDUs 5 1. UNODC, 2004; 2. Palepu, CMAJ 2001; 3. Kluytmans, Clin Micro Rev 1997; 4. von Eiff, NEJM 2001; 5. Basetti, Infection 2004

3. S Aureus Expresses Many Potential Virulence Factors Surface proteins that promote colonization of host tissues Factors that probably inhibit phagocytosis (capsule, immunoglobulin binding protein A) Toxins that damage host tissues and cause disease symptoms Coagulase-negative staphylococci are normally less virulent and express fewer virulence factors – S epidermidis readily colonizes implanted devices

4. Skin and Soft Tissue Infections (SSTIs) Among IDUs Include local (cellulitis & abscesses) and necrotizing (complicated abscesses, necrotizing fasciitis, pyomyositis, myonecrosis) SSTIs Most common organisms are S aureus > S pyogenes > polymicrobial infections Related to local tissue trauma, direct effect of drugs, tissue ischemia and inoculation of bacteria – Increased risks: “skin popping”, use of non-sterile needles, “speedballs”, “booting”, licking the needle – Decreased risks: use of alcohol preparation of skin – Unclear association: HIV and immunosuppression Ebright, ID Clin NA, 2002

5. Skin and Soft Tissue Infections

6. Invasive Infections Among IDUs Most common cause is S aureus >> Strep >>>> GNRs Most commonly include bacteremia from local source (lungs, SSTIs), endocarditis and osteomyelitis Endocarditis more likely to be Right-Sided among IDUs than among non-IDUs Duration of antibiotics is prolonged though some evidence of shorter duration for right- sided infections

7. Invasive Infections

8. Emergence of MRSA Hospital-acquired MRSA (h-MRSA) – Plasmid-mediated – Not associated with toxin production – Associated with recent hospitalization and use of antibiotics – Highly resistant to most oral antibiotics, except linezolid Community-acquired MRSA (c-MRSA) – Chromosomally-mediated – Associated with toxin production (Panton-Valentine leukocidin) – Person-to-person transmission and not associated with traditional risk factors [IDUs, sexual contact and crowding … athletes, prisoners, homeless shelters, day care centers) – Sensitive to many oral antibiotics (TMP/SMZ, tetracycline, etc.)

9. Surveillance of S aureus and MRSA in the United States Colonization 1 – S aureus: 89.4 million (32%) and MRSA: 2.3 million (0.8%) Hospitalization – ICUs (1974 – 2%; 1995 – 22%; 2004 – 64%) 2 – 292,000 per year; 126,000 (43%) due to MRSA 3 Skin and Soft Tissue Infections – 12 million outpatient visits per year for SSTIs 4 – 76% of purulent infections in 11 ERs secondary to S aureus 5 78% of these due to MRSA with overall MRSA rate = 59% Invasive Infections 6 – Occurs in 94,000 persons/year – Mortality = 19,000 – 86% are healthcare-associated 1. Kuehnert, JID, 2006; 2. Klevens, CID, 2006; 3. Kuehnert, Emerg ID, 2005; 4. McCaig, Emerging ID, 2006; 5. Moran, NEJM, 2006; 6. Klevens, JAMA, 2007

10. Staphylococcal Colonization Among IDUs is Increasing in North America Nasal carriage screening in 2000 (N=299) and 2006 (N=301) among active IDUs in Vancouver Increase in S aureus colonization: 27.1%   39.5% Increase in MRSA colonization: 7.4%  18.6% MRSA PFGE changed from primarily USA-500 (100%) to USA-300 (75%) with increasing susceptibility to TMP/SMZ and TCN with USA-300 Trend toward increased recent antibiotic use (p=.056) and hospitalization (p=0.12) for MRSA vs. MSSA Al-Rawahi GN, J Clin Microbiol, 2008

11. S Aureus Carriage Among IDUs in Methadone and Heroin Maintenance Programs 2001: 70 MM and 94 HM patients in Basel, Switzerland Nasal carriage higher in MM (43%) than in HM (23%) patients – No difference in recent or remote hospitalization – MM subjects more likely to have used antibiotics in previous month (12% vs 4%), be HIV+ (20% vs 6%) and have no IDU (34% vs 0%) In multivariate analysis, enrolled in MM was the only significant (AOR 2.27) correlate of S aureus colonization No MRSA isolated, 1 but subsequent studies have demonstrated MRSA transmission between drug users 2 and introduction of new MRSA strains 3 1. Bassetti, Inf Control Hosp Epi, 2004; 2. Qi, J Clin Micro 2005; 3. Fleisch, Infection, 2005

12. Colonization with MRSA in Opioid Dependent Patients Case control study of 60 hospitalized opioid dependent (OD) and 60 non-drug users in Egypt – Subjects with any CDC risk for h-MRSA excluded (time extended to five years for health care facility) Colonization higher in drug vs. non-drug users (30% vs 10%) – Increased risk associated with duration of drug use and use of non-prescription antibiotics – 58% of active MRSA infections associated with colonization El-Sharif, Exp Biol Med, 2008

13. Rapid Spread of MRSA in the Netherlands 200020012002 Year No. Hospitals with MRSA PFT-16No. MRSA Isolates Wannet, J Clin Micro 2004

14. Hospitalization and S Aureus

15. Managing MRSA Colonization Colonization persists for years, despite treatment of infection Contact precautions and isolation of wounds recommended Controversy exists around universal screening, isolation and at eradication of the carrier state

16. Changing Epidemiology of Staphylococcal Infections Antibiotic Year Introduced Years to Report of Resistance Years until 25% rate in hospitals Years until 25% rate in community Penicillin19411-2615-20 Vancomycin195640??? Methicillin1961<125-3040-50 (projected)

17. Summary IDUs exist on all continents and are more likely to be colonized with S aureus Morbidity and mortality related to S Aureus infections is greater among IDUs Colonization with S aureus, including MRSA, is associated with increased risk for infection Infection can be reduced with skin cleaning and sterile syringes MRSA prevalence is variable but growing in different regions of the world, thus requiring increased surveillance to guide clinical practice