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Are we being threatened by community acquired organism • 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 40C – abdominal mass felt in the left hypochondrial area. • 100cc of pus was aspirated • Staphylococcus aureus – Naficillin ----------------R – Erythromycin -----------S – Vancomycin ------------S – Clindamycin ------------S – Co trimexazole---------S – Cefazolin ----------------R – Ciprofloxacin------------S • An 18-month-old girl – fever – lambing • On physical examination – febrile 38.5C – swelling, redness, and marked tenderness over the upper one third of the left leg below the knee joint. • deep vein thrombosis of the left popliteal and posterior tibial veins • 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. Bilateral orbital abscess with extension probably through the eroded bone into the right temporal fossa (extradural collection) • 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 • Staphylococcus aureus – Naficillin ----------------R – Erythromycin -----------R – Vancomycin ------------S – Clindamycin ------------S – Co trimexazole---------S – Cefazolin ----------------R – Ciprofloxacin------------S CA MRSA 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 • Methicillin introduced in 1959, was specifically designed to be resistant to βlactamase degradation 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. • Recently, reports of MRSA infections acquired outside of the hospital setting have increased nationally, including fatalities. • 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 Definition of CommunityAcquired 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 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 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/euhssid030606.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 • risk for CA-MRSA infections – Limited time for hygiene – Sharing of personal items – Skin cuts & abrasions – Skin to skin contact – Crowding 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 Genetics of methicillin resistance • The mecA is carried on a mobile genetic element, (SCCmec) • 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 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 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 TOXIN ANALYSIS • PVL genes are associated with communityonset 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 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 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 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 Susceptibility testing • Several studies have showed that most CAMRSA 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) 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% 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. Prevention • Prompt attention to breaches of the skin • clean and dry • Keeping fingernails clean and cut short • changing towels, washcloths, underwear, and sleepwear daily 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 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 THANK YOU