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

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

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

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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

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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

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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

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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

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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

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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.

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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

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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

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SSI

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Options for treating both -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;138

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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;138

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Ceftaroline Tigecycline SSI TREATMENT

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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

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Uncomplicated: Vancomycin or daptomycin for at least 2 weeks Complicated: 46 weeks of therapy is recommended *variable BACTEREMIA TREATMENT Clinical Infectious Diseases2011;138

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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

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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

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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

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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;138

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IV vancomycin daptomycin clindamycin Linezolid TMP/SMX +/- rifampin BONE AND JOINT INFECTION Clinical Infectious Diseases2011;138

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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

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

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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-

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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

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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

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Penicillinase ANTIBIOTIC RESISTANCE IN S. AUREUS FOLLOWING DISCOVERY OF PENICILLIN

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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

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1940's

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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

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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 12 mg/L had a success rate of only 9.5% (p = 0.03). MIC CREEP J Clin Microbiol. 2004; 42:2398-402.

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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

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E. faecalis E. faecium VANCOMYCIN RESISTANT ENTEROCOCCUS

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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

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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

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

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