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M ethicillin R esistant S taphylococcus a ureus

M ethicillin R esistant S taphylococcus a ureus. Catherine D. Bacheller, MD Infectious Diseases Medical Director, Infection Prevention and Control KMC Assistant Professor of Medicine, WSU. Staphylococcus aureus : History of Acquired Resistance. glycopeptide intermediate resistant.

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M ethicillin R esistant S taphylococcus a ureus

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  1. Methicillin Resistant Staphylococcus aureus Catherine D. Bacheller, MD Infectious Diseases Medical Director, Infection Prevention and Control KMC Assistant Professor of Medicine, WSU

  2. Staphylococcusaureus: History of Acquired Resistance glycopeptide intermediate resistant penicillin resistant Multi-Drug Resistance 1945 1955 1965 1975 1985 1995 methicillin resistant mupirocin resistant

  3. Mechanisms of MRSA Antibiotic Resistance • Activated B-lactamase • Reduced PBP capacity • Chromosomal mecA gene Altered PBP Low affinity for B-lactams Causes resistance to all beta lactam antibiotics Mayer et al. Principles and Practice of Infectious Diseases. 1995; Eliopoulos. Infectious Diseases. 1992.

  4. Nosocomial Bloodstream Infections Fungi (8%) Gram Negative (27%) Gram Positive (64%) Edmond MB et al. Clin Infect Dis, 1999; 29: 239-244

  5. Nosocomial Bloodstream Pathogens Coagulase Negative Staphylococcus (32%) Other (11%) All Gram Negative (21%) Viridans Streptococci (1%) Staphylococcus aureus (16%) Candida (8%) Enterococci (11%) Edmond MB et al. Clin Infect Dis, 1999; 29: 239-244

  6. A Multi-Center Economic Analysis of MRSA Bacteremia LOS ICU LOS Mortality Cost (Days) (Days) ($) *P = 0.03; †P = 0.07 Welch KE, et al. 39th ICAAC. 1999, abstract

  7. 6-Month Impact of Resistance on LOS and Hospital Costs

  8. Nosocomial Infections with MRSA 60 Panlilio et al. Infect Control Hosp Epidemiol. 1992.

  9. Staphylococcus aureusICU Nosocomial Infections Lowy, NEJM 1998; 339:520-32

  10. promed@usa.healthnet.org Subject: PROMED: Infection Control: MRSA (3) Date: Thu, 6 Jun 1996 17:43:27 -0400 The issue about trying to contain MRSA is also very much about: 1. Cost to the hospital in vancomycin use (to treat MRSA infections and for empiric treatment in units where MRSA is endemic) 2. Microbial cost - potential for VRSA, emergence or selection of VRE and other vancomycin-resistant organisms.

  11. S aureus Is Most Common Bacterial Pathogen Isolated From SSTIs of Hospitalized Patients • Other organisms (320/1,562) represented 20.5% of the total bacteria recovered Adapted from Doern GV et al. Diagn Microbiol Infect Dis. 1999;34:67.

  12. SKIN AND WOUND INFECTIONS Impetigo Ecthyma Folliculitis Furunculosis Carbuncles Cellulitis Abscess Paronychia Surgical sites infections Burn infections Hidradentitis supprativa scalded skin syndrome BONE Osteomylelitis HEART Endocarditis Myocarditis LUNG Pneumonia JOINTS Septic arthritis BLOOD Septicemia Bacteremia INTESTINAL TRACT Food poisoning The Pathogenic Potential of S. aureus(associated sites) EYE Endophthalmitis VAGINA Toxic shock syndrome

  13. TOXINS a-toxin b-toxin g-toxin Enterotoxins A-J Exfoliative toxin A and B Panton-Valentine toxin Toxic Shock Syndrome Toxin ENZYMES b-lactamase Catalase Coagulase Cystein protease V8 protease Metalloprotease/aureolysin Staphopain Lipase Nuclease Thermonuclease PI-phospholipase C Staphylokinase Hyaluronidase Lipase/esterase Serine-like proteins SURFACE PROTEINS Clumping factor A/B Collagen binding protein Fibrinogen-binding protein Fibronectin-binding protein Lactoferrin-binding protein Protein A Laminin binding protein Staphylococcal Virulence Factors S. aureus is an adaptable opportunist -commensal to pathogenic -different sets of virulence factors may be important in different diseases Extracellular matrix-binding protein Vitronectin-binding protein Elastin-binding protein Bone sialoprotein-binding protein Serine-aspartate repeat protein

  14. Staphylococcal Infections

  15. Preventing Spread of MRSA Outbreak Among Hospitalized Patients • Timely ID of epidemic strain • Culture surveillance of patients and staff • Barrier precautions • Staff carriers to non-clinical duties • HANDWASHING !!!!!!!!! • Discharge of patients infected with epidemic strain • Flagging infected patients records

  16. National Clean Hands Weekat Kettering Hospital September 18-24, 2005

  17. Elimination of nasal carriage of methicillin-resistant Staphylococcus aureus with mupirocin during a hospital outbreak. During a hospital outbreak of methicillin-resistant S. aureus (MRSA), involving more than 200 patients, 40 patients and 32 hospital staff who were stable nasal carriers of MRSA received topical application of 2% mupirocin, formulated in a white soft paraffin and lanolin ointment, to their anterior nares for five days. ... … The elimination of nasal MRSA by mupirocin, and the introduction of isolation facilities, were associated with the control of the outbreak. Hill RL; Duckworth GJ; Casewell MW J Antimicrob Chemother 1988;22:377 - 84.

  18. promed@usa.healthnet.org Subject: PROMED: Infection Control: MRSA (3) Date: Thu, 6 Jun 1996 17:43:27 -0400 My personal impression is that there is probably a critical limit of MRSA prevalence beyond which control measures are largely futile (I hope to be proved wrong, perhaps by a case-control study of wards with and without control measures), and that control measures are most beneficial in hospitals which have a near-zero rate of MRSA.

  19. MRSA: No Longer Limited toNosocomial Infections in the USA Moreno et al. Clin Infect Dis. 1995.

  20. Methicillin Resistant Staphylococciby Treatment Setting Fridkin SK et al. Clin Infect Dis 1999; 29: 245-252

  21. Here comes community-acquired MRSA…

  22. MMWR, 48(32); 707-710. Aug 20, 1999

  23. Methicillin-resistant Staphylococcus aureus

  24. CA MRSA

  25. CA MRSA

  26. CA-MSRA in the Wisconsin News(Milwaukee Journal-Sentinel) “He got an extreme case. It got into his joint, then his bone, then spilled into his blood, causing him to become septic,” said the father, adding that “the pain is tremendous.”

  27. Subject: Tibia - MRSA osteomyelitis Vanderbilt University Date: Wed, 24 Dec 2003 06:11:14 -0600

  28. Characteristics of CA-MRSA • Community-acquired MRSA differs from HA-MRSA in that CA-MRSAis not multidrug-resistant and can usually be treated with clindamycin,trimethoprim/sulfamethoxazole, minocycline, or linezolid. • Both organismscarry the staphylococcal cassette chromosome mecA (SCCmecA)gene that encodes resistance to the ß-lactams

  29. Emerging Infectious Diseases • Vol. 9, No. 8, August 2003

  30. We assessed whether any common genetic markers existed among 117 CA-MRSA isolates from the United States, France, Switzerland, Australia, New Zealand, and Western Samoa by performing polymerase chain reaction for 24 virulence factors and the methicillin resistance determinant. Limited number of clones found Although the selective advantage conferred by the combination of genetic traits (i.e., PVL locus and SSCmec IV in an agr3 background) is not clear, the spread of a limited number of clones in each continent suggests that these CA-MRSA strains are particularly suited to be successful community-based pathogens.

  31. Involvement of Panton-Valentine Leukocidin Producing Staphylococcus aureus in Primary Skin Infections and Pneumonia. • Panton-Valentine leukocidin (PVL) is a cytotoxin that causes leukocyte destruction and tissue necrosis. It is produced by fewer than 5% of Staphylococcus aureus strains. • A collection of 172 S. aureus strains were screened for PVL genes by polymerase chain reaction amplification. • PVL genes were detected in 93% of strains associated with furunculosis and in 85% of those associated with severe necrotic hemorrhagic pneumonia (all community-acquired). They were detected in 55% of cellulitis strains, 50% of cutaneous abscess strains, 23% of osteomyelitis strains, and 13% of finger-pulp infection strains. • PVL genes were not detected in strains responsible for other infections, such as infective endocarditis, mediastinitis, hospital-acquired pneumonia, urinary tract infection, and enterocolitis, or in those associated with toxic-shock syndrome. It thus appears that PVL is mainly associated with necrotic lesions involving the skin or mucosa. Gerard Lina, et al. Clinical Infectious Diseases    1999;29:1128-1132..

  32. Pneumonia

  33. CA MRSA Inpatient Therapy Bacteremia • Vancomycin 1gm q 12hr (target trough 10-20) • Daptomycin 6mg/kg q 24hr • Quinupristin-dalfopristin 7.5mg/kg q 8hr via CVP Ventilator Associated Pneumonia • Linezolid 600mg q 12hr (?superior) • Vancomycin 1gm q 12hr • (DO NOT USE Daptomycin)

  34. CA MRSA Outpatient Therapy I & D of abscess and Culture of fluid Oral antibiotics for 2 weeks: • Clindamycin 300mg q 6hr (inducible resistance) • TMP/SMZ DS q 12hr (not active in pus) ?plus Rifampin 300mg q 12hr • Minocycline or Doxycycline 100mg q 12hr • Linezolid 600mg q 12hr ($$$$) If recurrent infection, repeat above plus:Nasal & Nails: Mupirocin BID x 5days Skin: Chlorhexidine (CHG) bath daily

  35. Methicillin-resistant Staphylococcus aureus: a consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management. ...MRSA colonization precedes infection. A major reservoir is the anterior nares. MRSA is usually introduced into an institution by a colonized or infected patient or health care worker. The principal mode of transmission is via the transiently colonized hands of hospital personnel... Mulligan ME; Murray-Leisure KA; Ribner BS; Standiford HC; John JF; Korvick JA; Kauffman CA; Yu VL. Am J Med 1993;94:313

  36. Handwashing is the single most important means of preventing the spread of infections

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