2. Are we being threatened by community acquired organism

3. 4 years-old Pakistani boy –fever for 4 weeks duration, –given amoxicillin syrup for 10 days –One week prior to admission, he developed abdominal distention. On physical examination –febrile 40  C –abdominal mass felt in the left hypochondrial area.

5. 100cc of pus was aspirated Staphylococcus aureus –Naficillin ----------------R –Erythromycin -----------S –Vancomycin ------------S –Clindamycin ------------S –Co trimexazole---------S –Cefazolin ----------------R –Ciprofloxacin------------S

6. An 18-month-old girl –fever – lambing On physical examination –febrile 38.5  C –swelling, redness, and marked tenderness over the upper one third of the left leg below the knee joint.

8. deep vein thrombosis of the left popliteal and posterior tibial veins

10. A 3 months old girl –fever at the age of 6 weeks –diagnosed to have pharngitis –given amoxacillin syrup for 5 days. –fevers subside for one week, –she develops fever again with proptosis of the right eye.

11. Bilateral orbital abscess with extension probably through the eroded bone into the right temporal fossa (extradural collection)

13. incision and drainage of the abscess through the medial side of Rt eye was done by the oculoplastic surgeon pus was sent for culture. CSF : WBC 2400

15. Staphylococcus aureus –Naficillin ----------------R –Erythromycin -----------R –Vancomycin ------------S –Clindamycin ------------S –Co trimexazole---------S –Cefazolin ----------------R –Ciprofloxacin------------S

17. CA MRSA

18. Introduction Staphylococcus aureus has been responsible for a great deal of human morbidity and mortality throughout history The introduction of penicillin in the1940s greatly improved the prognosis for patients with severe staphylococcal infections

19. Methicillin introduced in 1959, was specifically designed to be resistant to β- lactamase degradation

20. Introduction (MRSA) was first reported in the United Kingdom in 1961 Over the past several decades, infections with (MRSA) among hospitalized patients have become common.

21. Recently, reports of MRSA infections acquired outside of the hospital setting have increased nationally, including fatalities.

22. CA-MRSA is new strain of MRSA presenting from community in person without tradition risk factor for MRSA differing from HA-MRSA in terms of : –Epidemiology –Abx sensitivity patterns –Virulence –Presentation –Treatment

23. Definition of Community- Acquired MRSA: culture positive for MRSA should be in the outpatient setting or within 48 hours after admission to the hospital The patient has no medical history in the past year of: –Hospitalization –Admission to a nursing home –Dialysis –Surgery –Permanent indwelling catheters or percutaneous medical devices

24. epidemiology Studies in both adults &pediatrics have shown 15 to 45% increase in S.aureus that are methicillin resistant,and large increase (up to 20 fold) in frequency of CA-MRSA infection in children » Current opinion in pediatrics 2005,17:67-70

25. epidemiology In Atlanta ; 72 % of community-onset Staph skin and soft tissue infections are now due to MRSA »www.eurekalert.org/pub_releases/2006- 03/euhs- sid030606.phpwww.eurekalert.org/pub_releases/2006- 03/euhs- sid030606.php In a Rural American Indian Community –Of S.aureus isolates, (45%) MSSA (55%) MRSA – (74%) of the MRSA, infections were classified as community acquired. »http://jama.ama-assn.org/cgi/content/abstract/286/10/1201

26. epidemiology In Finland: From1997 to 1999 one study found that of total MRSA-positive persons, 21% had community -acquired »http://www.cdc.gov/ncidod/eid/vol8no6/01-0313.htmhttp://www.cdc.gov/ncidod/eid/vol8no6/01-0313.htm

27. risk for CA-MRSA infections –Limited time for hygiene –Sharing of personal items –Skin cuts & abrasions –Skin to skin contact –Crowding

28. Genetics of methicillin resistance mechanisms of methicillin resistant –hyperproduction of b-lactamases –modification of normal PBP –presence of an acquired PBP( PBP2a)encoded by the mecA gene »Ubukata K,etal,Antimicrob Agents Chemother 1999;33:1624–6 The methicillin-resistance gene (mecA) is not present in methicillin-susceptible strains and is believed to have been acquired from a distantly related species »Enright MC,etal; Proc Natl Acad Sci USA 2002;99:7687–92

29. Genetics of methicillin resistance The mecA is carried on a mobile genetic element, (SCCmec)

32. CA-MRSA harboring SCCmec type IV has been demonstrated to replicate more rapidly than HA-MRSA isolates with other SCCmec types This may account for its remarkable success in displacing other MRSA strains in some hospitals after its introduction from the community »Okuma K,etal; J Clin Microbiol 2002;40:4289–94

33. CAMRSA Characteristic: Pulse field gel electrophoresis (PFGE) pattern Toxin genes: Enterotoxins (not present) Toxins shock – associated toxins (not present) Panton – Valentine leukocidin (present) Mec A cassette and subtype (mec IV ) Resistance pattern

35. TOXIN ANALYSIS Panton – Valentine Leukocidin (PVL) –first reported in 1932 –Combination of 2 proteins (Luk S and F) –Potent mediator of inflammation and activator of leukocytes –PVL destroys leukocytes by creating lytic pores –Associated with necrotic infections

36. TOXIN ANALYSIS In a study by Naimi et al., PVL genes were identified in (77%) CA-MRSA isolates compared with (4%) in HA MRSA »Naimi TS,etal. JAMA 2003;290:2976–84. A study in France seeking to determine the clinical and bacteriologic characteristics of their CA-MRSA detected their first case in 1999 and a total of 14 cases by the end of 2001. PVL was present in all 14 of their community acquired isolates »Dufour P,etal. Clin Infect Dis 2002;35:819–24

37. TOXIN ANALYSIS PVL genes are associated with community- onset staphylococcal skin infections and necrotizing pneumonia PVL-producing S. aureus are rarely responsible for other infections such as septicemia, and endocarditis »Vandenesch F,etal. Emerg Infect Dis 2003;9:978–84

38. Susceptibility testing detecting oxacillin (methicillin) resistance in staphylococci that possess the mec gene may be difficult because these strains exhibit heteroresistance The observation of multiple resistance is a clue for the microbiologist to the possibility of methicillin resistance CA-MRSA resistant to b-lactam antibiotics only, making it difficult to suspect methicillin resistance

39. Susceptibility testing to enhance the expression of oxacillin resistance –incubation of tests at temperatures no greater than 35 C –obtaining final readings after a full 24 hours of incubation –supplementation of Mueller-Hinton broth or agar with 2% NaCl for dilution tests »National Committee for Clinical Laboratory Standards; 2003

40. Susceptibility testing NCCLS recommends performing standard disk diffusion test with cefoxitin (30 micg) disks for detection of oxacillin (methicillin) resistance »National Committee for Clinical Laboratory Standards; 2004

41. Susceptibility testing Several studies have showed that most CA- MRSA strains are susceptible to clindamycin »Martinez-Aguilar G,etal. Pediatr Infect Dis J 2003;22:593–8 Indusable resistant to clindamycin –efflux pump encoded by msr genes –ribosomal methylase, encoded by erm genes (MLSB phenotype)

43. Rapid methods for detection of methicillin resistance The detection of the mecA gene by PCR considered the ‘‘gold standard’’ for the detection of MRSA strains Velogene Rapid MRSA Identification Assay colorimetric enzyme immunoassay that uses a fluorescein- labeled mecA gene probe sensitivity of of 97% specificity of 100%

44. Rapid methods for detection of methicillin resistance The MRSA-Screen –is a slide latex agglutination test using latex particles sensitized with a monoclonal antibody against PBP2a »Swenson JM,etal. J Clin Microbiol 2001;39:3785–8.

46. Prevention Prompt attention to breaches of the skin clean and dry Keeping fingernails clean and cut short changing towels, washcloths, underwear, and sleepwear daily

47. Prevention Cochrane review did not find topical antibiotics to be useful for eradicating nasal MRSA applying mupirocin to the anterior nares may be useful to diminish nasal colonization by CA-MRSA and decrease the likelihood of recurrences »Chen SF: Staphylococcus aureus decolonization. Pediatr Infect Dis J 24: 70-80, 2005

48. Prevention taking a bath twice a week for 15 minutes in water mixed with regular strength Clorox (one teaspoon per gallon of water) appears to be helpful in preventing recurrent infections »Chen SF: Staphylococcus aureus decolonization. Pediatr Infect Dis J 24: 70-80, 2005

49. THANK YOU