1. CPC #2: Fever, cough, dyspnea, and change in mental status Barbara J. Crain, M.D., Ph.D. October 7, 2008

2. Heart  Borderline cardiomegaly Hypertensive changes Heart weight 460 gm for height: 229=399 gm for weight 241-481 gm Occasional “boxcar nuclei”  Mild to moderate coronary atherosclerosis

3. Kidney  Nephrosclerosis  Arteriolosclerosis  Hypertensive changes

4. Brain (striatum) Dilated perivascular spacesArteriolosclerosisPerivascular hemosiderin Hypertensive changes in blood vessels

5. Brain (deep cortical white matter) Normal white matter (H&E)Normal astrocytes (GFAP)Reactive astrocytes (GFAP) Focal pallor and reactive astrocytosis, most likely hypertensive in origin

6. Liver  Mild acute congestion  Mild macrosteatosis  Mild nonspecific inflammation of triads  No evidence of fibrosis, cirrhosis, or alcoholic hepatitis

7. Lungs – gross examination  Small pleural effusions  Markedly increased weight: 2,900 gm (reference 685 – 1,050 gm)  Firm, red parenchyma, most marked in right lung  2-cm cavitary lesion in right upper lobe  Gross impression: severe bronchopneumonia with abscess

8. Lung abscesses

9. Lung with congestion and hemorrhage

10. Lung with hemorrhage, necrosis

12. Lung with hemorrhage, necrosis and bacteria: pneumonia in leukopenic patient

13. Gram-positive cocci

14. http://swampie.files.wordpress.com/2008/02/staphylococcus-aureus.jpg http://images.encarta.msn.com/xrefmedia/sharemed/targets/images/pho/t028/T028362A.jpg ??

15. Blood culture from night of admission ORG 1: METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS IN ANAEROBIC BOTTLE -------------------------------------------------------------- RESULT ANTIBIOTIC MIC (mcg/ml) INTERPRETATION Oxacillin ------------- >2 -------------- Resistant Vancomycin ------------- 2 ------------ Susceptible Staphylococcal isolates that are resistant to oxacillin (MRS) should not be treated with penicillins, beta-lactam/beta-lactamase inhibitor combinations, cephalosporins and carbapenems.

16. Sputum culture 1. BACT MICRO EXAM TYPE 2 - ADEQUATE SPECIMEN. MANY POLYMORPHONUCLEAR CELLS AND MANY SQUAMOUS EPITHELIAL CELLS. MANY NORMAL UPPER RESPIRATORY FLORA 2. BACTERIOLOGY CULTURE MODERATE MIXED RESPIRATORY FLORA AT 1 DAY POSITIVE AT 1 DAY ORG 1: HEAVY METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS

17. Major autopsy findings  Severe hemorrhagic and necrotizing bronchopneumonia with abscess formation, right > left  Culture-positive for MRSA  Chronic changes associated with hypertension Borderline cardiomegaly Arteriolonephrosclerosis of kidneys Hypertensive cerebral vascular disease Focal chronic white matter damage  Mild to moderate coronary atherosclerosis

18. Cause of death Part I a)Sepsis (due to or as a consequence of) b)Acute MRSA bronchopneumonia with abscess formation Part II a)Atherosclerotic vascular disease b)Hypertension c)Cardiomegaly d)History of smoking

19. Hospital-acquired MRSA infections  First described in 1960, increasing problem in 1980’s  MSSA vs. MRSA: includes a large genetic element ; staphylococcal cassette chromosome mec (SCCmec)  SCCmec carries the mec gene complex and various resistance genes against non ß-lactam antibiotics  Over half the Staph isolates in some hospitals are now MRSA  Infections often in very ill patients, particularly in ICUs  Bacteremia, pneumonia, endocarditis  High morbidity and mortality Clin Infect Dis 2008; 46:S344-49 Brit J Anaesth 2004;92:121-130

20. Community-acquired MRSA infections  More often children and young adults without underlying illnesses  Generally skin / soft tissue infections (cellulitis, abscess)  Emerging problems: necrotizing fasciitis, Waterhouse-Friedrichsen syndrome, empyema, necrotizing pneumonia  Person-to-person transmission  Strains causing CA-MRSA going back into hospitals http://www.jems.com/Images/mrsa_tcm16-33808.jpg

21. Community-acquired MRSA pneumonia  Rapidly progressive necrotizing pneumonia  Effusions, bacteremia common  Primarily children, young adults  High mortality rate (>50% in some series)  Median survival time 4-7 days  Often preceded by viral-like illness (particularly influenza A) Emerg Infect Dis 2006;12:498-500 MMWR 2007;56  14):325-329 Ann Clin Microb Antimicrob 2008;7:1

22. Pathogenesis of CA-MRSA  Well characterized strains: USA300 most common in US  Basis for apparent increased virulence Increased fitness of bug? Improved evasion of host immune system? Unique toxin production?  Panton-Valentine leukocidin (PVL) gene: toxin with leukocytolytic and dermonecrotic activity Clin Infect Dis 2008; 46:S350-5 http://a.abcnews.com/images/Health/ld_mrsa_080425_mn.jpg9

23. http://www.health.alberta.ca/influenza/SC_handwashing.jpg Prevention of MRSA

24. http://www.health.alberta.ca/influenza/SC_handwashing.jpg