TACKLING THE MRSA EPIDEMIC Paul D. Holtom, MD Associate Professor of Medicine and Orthopaedics USC Keck School of Medicine MRSA Trend (HA + CA) in US TSN Database USA (1993-2003) % of MRSA among S. aureus Isolates 45 40 35 30 25 20 15 10 25.1 26.2 CA-MRSA 29.1 36.0 42.5 48.5 1993 1995 1997 1999 2001 2003 Year MDR = multidrug resistant, CA = community-acquired. TSN Database, USA, Focus Technologies. Data on file, Ortho-McNeil Pharmaceutical, Inc. Evolution of Drug Resistance in S. aureus Penicillin Methicillin S. aureus Penicillin-resistant Methicillinresistant [1960s] [1950s] S. aureus S. aureus (MRSA)
METHICILLIN RESISTANCE IN S. AUREUS 1961: First reports in Europe 1965: First hospital outbreak in US Barber. J Clin Path 14:385; 1961 Jevons. Br. Med J. 1:124, 1961 Barrett. NEJM. 279:441, 1965 METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS Contains meca gene for PBP-2a PBP-2a has low affinity for all _ lactams: Penicillins Cephalosporins Carbapenems meca gene located on mobile element integrates into specific site of chromosome Evolution of Drug Resistance in S. aureus Penicillin Methicillin S. aureus Penicillin-resistant [1960s] [1950s] S. aureus S. aureus (MRSA) [1997] Vancomycin Vancomycinresistant S. aureus Vancomycin Methicillinresistant intermediateresistant S. aureus (VISA) [1990s] Vancomycin-resistant enterococci (VRE)
HEALTH-CARE ASSOCIATED MRSA Prevalence of MRSA Proportion of S. aureus Nosocomial Infections Resistant to Oxacillin (MRSA) Among Intensive Care Unit Patients,1989-2004 70 2004 60 63% 50 Percent Resistance 40 30 20 10 0 *Source: NNIS System. 1989 1991 1993 1995 1997 1999 2001 2003 Year Centers for Disease Control and Prevention Web site. Available at: http://www.cdc.gov/ncidod/dhqp/pdf/ar/icu_restrend1995-2004.pdf. Accessed March 6, 2006. METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS Classical hospital-acquired ORSA Contains SCCmec Types [I,] II, or III Usually shows resistance to: Tetracyclines Macrolides Quinolones Rifampin Aminoglycosides
HA-MRSA Strains show multi-drug resistance Not spread in the community setting?slower growth than OSSA?lack of antibiotic pressure in environment Risk Factors for MRSA Setting Hospitals Long-Term Care Facilities Risk Factors for Infection and Colonization ν Previous hospital stay 1,2 ν Prolonged length of stay prior to infection 1 ν Surgical procedure(s) 1 ν Enteral feeding 1 ν Levofloxacin use 1 ν Presence of decubitus ulcer 3 ν Presence of wounds 3 Prior Antibiotic Exposure 4,5 ν Third-generation cephalosporins 6 ν Fluoroquinolones 1,7,8 1.Graffunder EM, Venezia RA. J Antimicrob Chemother. 2002;49:999-1005. 5.Law MR et al. Epidemiol Infect. 1988;101:623-629. 2.Asensio A et al. Infect Control Hosp Epidemiol. 1996;17:20-28. 6. Peacock JE et al. Ann Intern Med. 1980;93:526-532. 3.Terpenning MS, et al. J Am Geriatr Soc. 1994;42:1062-1069. 7. Evans ME et al. J Antimicrob Chemother. 1998;41:285-288. 4.Hershow RC et al. Infect Control Hosp Epidemiol. 1992;13:587-593. 8.Harbarth S et al. Clin Infect Dis. 2000;31:1380-1385. Risk Factors Associated Independently with MRSA Infection Risk Factor OR 95% CIs P Value Levofloxacin use 8.01 3.15, 20.3 <0.001 Enteral feeding 2.55 1.37, 4.72 0.003 Surgery 2.24 1.19, 4.22 0.01 Previous hospitalization Length of stay before culture 1.95 1.03 1.02, 3.76 1.0, 1.07 0.04 0.05 Graffunder EM, Venezia RA. J Antimicrob Chemother. 2002;49:999-1005.
HA-MRSA INFECTIONS BY ORGAN SYSTEM Urinary tract 20% Other 12% Skin soft tissue 36% Bloodstream 9% Respiratory 22% Otitis media externa 1% Naimi TS et al. JAMA. 2003;290:2976-2984 Mortality Associated with Bacteremia Due to MRSA vs. MSSA Outcome Recovered MRSA-infected Patients 70.4% MSSA-infected Patients 86.4% Died of other causes Died of infection* 17.8% 11.8% 8.5% 5.1% *P<0.001 Melzer M, et al. Clin Infect Dis. 2003;37:1453-1460. S. aureus Surgical Site Infections : Impact of Methicillin Resistance on Outcomes All-cause 90-day mortality, unadjusted (%) 30 20 10 0 25/121 Independent effect of MRSA: OR 3.4 (95% CI 1.5-7.2, P = 0.003) After adjusting for age, ASA score, duration of surgery 11/165 4/193 MRSA MSSA Controls ASA Score: American Society of Anesthesiologists score of pre-operative physical fitness Engemann JJ, Carmeli Y, Cosgrove SE, et al. 2003 Clin Infect Dis. 36:592-598.
COMMUNITY ASSOCIATED MRSA COMMUNITY ASSOCIATED MRSA (CA-MRSA) Different from HA-MRSA Epidemiologically Clinically Genetically CDC Definition of CA-MRSA Diagnosis of MRSA made in the outpatient setting OR culture positive for MRSA 48 hr of hosp admission No medical history of MRSA colonization or infection www.cdc.gov
CDC Definition of CA-MRSA No medical history in the past year of: Hospitalization Admission to nursing home, SNF or hospice Dialysis Surgery No indwelling catheters or medical devices that pass through the skin www.cdc.gov MRSA AS COMMUNITY PATHOGEN Associated with SSTI CA-MRSA Urinary tract 1% Bloodstream 4% Respiratory 6% Otitis media externa 7% Other 8% Skin soft tissue 74%
MRSA AS COMMUNITY PATHOGEN Associated with SSTI Genetically different than HA-MRSA SCCmec Type IV CA-MRSA TOXINS Panton-Valentine leukocidin Superantigen enterotoxin H 15 additional unique superantigen genes 11 exotoxin genes 4 enterotoxin genes Strain MW2 demonstrated 10 times stronger human-t cell proliferation than other S. aureus strains May correlate with high virulence Baba T, et al. Lancet. 2002;359(9320):1819-1827
RISK FACTORS FOR CA-MRSA IVDU MSM Correctional institutions Homelessness/marginally housed CA-MRSA in CORRECTIONAL FACILITIES Los Angeles County Jail (N=165,000) 2002: 928 inmates with MRSA infections 66 hospitalized, most with SSTI 10 with invasive disease (bacteremia, endocarditis, osteomyelitis) 2003: 1849 cases 2004: 2480 cases MMWR. 2003;52(5):88 Ngo V, et al. Abstract 32, SHEA, 2005
CA-MRSA in CORRECTIONAL FACILITIES Folliculitis, furuncles, boils, abscesses Spider bites Risks: previous antibiotics, skin trauma, sharing soap, hand-washing clothes, self-draining boils, recent arrival to facility MMWR. 2003;52(5):88 Tobin et al. IDSA 2003 CA-MRSA in COMPETITIVE ATHLETES Wrestlers (Indiana) 2 wrestlers from different weight groups Fencing club (Colorado) Skin abscesses, paraspinal myositis, bacteremia Risks: sharing sensor wires? shared clothing MMWR. 2003;52(5):88 CA-MRSA in COMPETITIVE ATHLETES Collegiate football players in Pennsylvania, Wisconsin, California Professional football players Miami Dolphins St. Louis Rams 5 of 58 players (9%); 8 infections Lineman or linebackers MMWR. 2003;52(5):88 NEJM 2005; 352:468-475
RISK FACTORS FOR CA-MRSA IVDU MSM Correctional institutions Homelessness/marginally housed Athletes Post-influenza pneumonia Clinical Implications of CA-MRSA Outpatient & Emergency Dept settings Consider medical practice modification in areas with high prevalence of CA-MRSA: More frequent C & S testing of potential S. aureus skin infections, especially in pediatrics Surgical drainage of infection, when appropriate Careful selection of empiric antibiotics for suspected staphylococcal infections when treatment is indicated Careful patient and laboratory follow-up Naimi et al. JAMA 2003;290:2976-84 THERAPEUTIC OPTIONS Community-acquired MRSA Frequently sensitive to multiple drugs Old, inexpensive drugs such as TMP/SMX, tetracycline, clindamycin can often be used
THERAPEUTIC OPTIONS Community-acquired MRSA Frequently sensitive to multiple drugs Old, inexpensive drugs such as TMP/SMX, tetracycline, clindamycin can often be used Hospital-acquired MRSA Usually multi-drug resistant THERAPEUTIC OPTIONS Glycopeptides (Vancomycin) Streptogramins (Synercid) Oxazolidinones (Linezolid) Daptomycin Tigecycline (Glycylcycline) COMING NEW DRUGS Telavancin Ceftibiprole
PREVENTION OF MRSA Impact of Hand Hygiene on Hospital Infections Year Author Setting Impact on Infection Rate 1977 Casewell adult ICU Klebsiella decreased 1982 Maki adult ICU decreased 1984 Massanari adult ICU decreased 1990 Simmons adult ICU no effect 1992 Doebbeling adult ICU decreased with one versus another hand hygiene product 1994 Webster NICU MRSA eliminated 1995 Zafar nursery MRSA eliminated 1999 Pittet hospital MRSA decreased Source: Pittet D: Emerg Infect Dis 2001;7:234-240 Link to: Improving hand hygiene FINAL THOUGHTS ON MRSA CA-MRSA is spreading rapidly and may become the dominant strain soon both in hospitals and community No new oral drugs will be released in the near future High index of suspicion and good hand hygiene are key to treatment and prevention
Human destiny is bound to remain a gamble, because at some unpredictable time and in some unforeseeable manner, nature will strike back. Mirage of Health, Rene Dubos, 1959 THANK YOU