MRSA (Methicillin Resistant Staph.

aureus)Geog 380

GENERAL COMMENTS about resistance

Inevitable “dance” of co-evolution Post WW II—steadily growing Widespread overuse Use in cattlefeed

“The way to the wound is through the nose”--Creech II et al, 2006

Chronology of MRSA

First reported UK 1961 First reported USA 1968 Community associated MRSA

(CA-MRSA) first reported 1980– Initially US– Pts lack risk factors for MRSA

CA-MRSA Georaphically Dispersed (community

acquired) Australia--Aboriginals/native

peoples Native Americans in US--rural Subpopulations in US

– IDUs– Prisoners– Sports players– kids

Bilateral Necrotizing Fasciitis--Pseudomonas

Source: Akamine et al, Internal Medicine 2008;47:553-6

Paradigms of CA-MRSA

It spread from hospital– Patients– Visitors– Staff

Current findings– It has been in reservoirs in community– The strain has been different than

hospital MRSA– Some nosocomial MRSA is CA-MRSA!!!!

Sobering Quotes

“Community-associated…MRSA now appears to be among the most common etiologies of skin and soft tissue infections.”

“MRSA may be replacing methicillin-susceptible S.

aureus (MSSA) as the typical community

staphylococcal strain.”

“it is difficult to justify using drugs like

cephalexin…if it is known that the majority of

patients will be infected with resistant isolates.”See Moran and Talan, Annals of

Emergency Medicine, 2004;11:321-22.

Prevalence of CA-MRSA

No national data collected Community data difficult to get Hospital data easier Varies 76% of MRSA in AK to

12% MN for soft tissue infections Huang et al, Journal of Clinical

Microbiology 2006;44:2423-27

Hospital MRSA

Formerly:–Few large university hosps– ICUs

Now:–97% teaching hosps report MRSA

Risk factors:– Long hospital stay, surgery,

catheter sites (prop to # of sites), long or recurrent exp to abx’s

Evidence of CA-MRSA Increase

10/100,000 admissions, kids, 1988-90 259/100,000 1993-5 See Herold et al, JAMA 1998;279:593-8 1993: 2,000 MRSA 2005: 368,000 APIC: 46/1000 hosp adm had life threatening

MRSA CDC: 94,000 life threatening hosp MRSA infs

and 19,000 deaths!!!! STAY HEALTHY

Frazee Study (Frazee et al, Annals of Emergency Med, 2005;45:31-20

Done in ER in Alameda County, CA 18% homeless, 28% IDU, 63% w abscess,

26% admitted to hosp

Nearly 50% patients w/ skin and soft tissue infections MRSA

74% of staph was MRSA “When skin and soft tissue infections require

antibiotic therapy, we recommend choosing an agent that is active against MRSA”

Findings of Huang et al

45% of pts w/MRSA had community associated MRSA

Not susceptible to usual abx’s for soft tissue infections but susceptible to:– TMP/SMX (Bactrim or Septra)– Gentamicin– Rifampin– Vancomicin– Clindamicin

Necrotizing Fasciitis

“flesh eating bacteria” Fairly rate Spectacular Life-threatening Surgical emergency Polymicrobial

– Toxin producing– Necrosis of fascia

Historical Background

Hippocrates 5th Cent BCE 19th C:

– “gangrenous ulcer”, “malignant ulcer”, “putrid ulcer”, phagedema gangrenosa

1800’s– Feared in the military…

Confused by multiple terms@ present

Epidemiology

Estimated 500-150 cases/yr in US Not specific by age or sex Increased risk in:

– IVDU– Alcoholics– Immunosuppressed– Peripheral vascular disease– diabetics

Typical Presentation

Any break in the skin Increased risk w/trauma

– Penetrating– Blunt– Surgical wound– IVDU– SC drug use– Perirectal abscesses– Bites– Da da da da

Clinical Presentation

Within 7 days of “injury” Red, swollen, tender, hot, painful

area Pain out of proportion to

physical findings Pain extends beyond boundaries

of erythematous area Rapid, rapid expansion

CFR

Typically 75%– Sepsis– ARDS

Higher at Harborview

WARNING: SOME SLIDES AFTER THIS GET VERY GRAPHIC. NO KIDDING

Hsiao F and Hsieh C. N Engl J Med 2008;358:940

A 65-year-old woman with a 15-year history of diabetes presented with fever (temperature, 38.5{degrees}C), chills, malaise, and a rash on the medial surface of the right thigh, vulva, and

lower abdominal wall (Panel A)

Necrotizing Fasciitis of Left Lower Leg

Source: Kihiczak et al, JEADV

Nec Fasc of the Perineum

Infections and Layers

Source: Chest 1996

NDM-1New Delhi Metallo-beta-

lactamase-1

HUH????

“What’d the dude say?” “Sounded like he was barfing” “I’m texting my girlfriend. How

do you spell that?” “Will it be on the test?” “You mean this isn’t Philosophy

101”?

NDM-1

Not a specific bacterium A genetically coded mechanism in

gram negatives (klebsiella, etc), E. coli

Cleaves ring in carbapenems (carbapenamase)

Relatively new broad spectrum antibiotics including imipenem, meropenem

Why should we care?

Renders a major class of antibiotics useless

These antibiotics are frequently the only effective ones against enterobaceteriacae

Also many other pathogens Few if any treatments then work

Lancet ID, April 7, 2011

“such pathogens typically are resistant to multiple other antibiotic classes, leaving very few treatment options available”

So let me explain

Enzyme is made by the bacterium based on instructions from its genome

This attacks the chemical structure of the “new” class of antibiotics

Cuts a ring Neutralizes the antibiotic

Journal of Chinese Medical Association, Nov. 2010

NDM-1 in Water Supply, New Delhi Source: Lancet ID, 4-2011