Methicillin Resistant Staphylococcal Aureus: An Emerging Threat With Increasing Pathogenicity and Antibiotic Resistance

By: Cortney A. Stringer, PA-SMentor: Dr. Frank Romanelli

WHERE IT ISColonizes 1/3 US population

Salt and heat tolerant up to 140 degrees Fahrenheit

S. aureus can be opportunistic to cause infection dwelling on inanimate objects for up to 2 mos (Bauman, 2004)

Prevalent in hospital settings, termed hospital associated (HA)MRSA

Smaller incidence in community setting with historically less pathogenicity and resistance, CA-MRSA

HA-MRSACan spread via contaminated hands or garments of healthcare workers to vulnerable patients

Secondary transmission from contaminated objects and hospital equipment

Immunocompromised patients are a particular target

Pts with HIV, CA, diabetes, pneumonia, dermatological abrasions or psoriasis, and dialysis pts; pts needing routine procedures with catheters, post op pts introduced to prosthetics

CA-MRSAStrains of MRSA that have arisen in community apart from nosocomial strains

Becoming a more frequent occurrence

Among people having healthcare contact or no healthcare contact

Babies coddled by healthcare parents, esp problem with small immunities

School age children spreading bacteria to classmates

Locker rooms and athletic equipment in gyms and organized sports leagues

Nursing homes, rehabilitation centers, prisons

CA-MRSAUntil recently, MRSA infections in community have presented as skin infections perhaps necessitating I&D and sometimes Abx prophylaxis

These strains resembling HA counterparts molecularly and in morbidity/mortality consequence

Other infections are including diseases of increased severity (e.g. sepsis, endocarditis, pulmonary emboli, extensive soft tissue infections, bone destruction)

Baba, et. al studies CA-MRSA41 strains typified using BURST technology and are mutating to resemble HA strains

Strains including SCC type III and IV

Concluded that type IV SCC strains exhibited increased mobility and thus increased propensity for genetic diversity

CA-MRSA bigger problem?ALL type IV strains demonstrated resistance to one additional Abx aside from beta lactams and 3 of such strains demonstrated multi dx resistance

In addition, such CA-MRSA strains were differentiated from others with 19 more genes for virulence

HOW DID WE GET TO THIS POINT?

S. aureus Evolutionary HXIncidents of resistance to penicillin first reported in 1920s

By 1940s nosocomial resistance approaching 25%

Methicillin introduced in 1959

By 1961 United Kingdom reports MRSA

By 1970s MRSA reported in 25% of hospitalized pts (CDC 2001)

HX cont.Staphylococcus aureus first evolutionary change included a penicillinase enzyme to inactivate the beta lactam ring, the bactericidal element of penicillin

Next change, mecA gene that encodes for altered penicillin binding protein. This mecA gene resides within a mobile cassette chromosome (SCC element), allowing for easy evolutionary change. As a locus on SCC, the mecA gene can code for resistance and pathogenicity to transfer to descendent staph strains

Result, penicillin and other beta lactam ring Abx useless (Enright, et al)

HX cont.

Some researchers think MRSA strains originated from a single methicillin susceptible s. aureus (MSSA) progenitor

Others hypothesize that these methicillin resistant strains stem from many different MSSA ancestors

Studying LineageDesirable because determining MRSA lineage from MSSA with respect to mutations can enable prediction of future strains can generate better tx options

912 typified staphylococcus aureus strains

Results show that these strains have developed genetic components allowing for easy transmission into hospitals, and then acquisition of mecA

Researchers (Enright, et. al) tell of “depressing evolutionary resistance” if this mechanism occurs with vancomycin

Another study reports 8 case studies of s. aureus infections with vancomycin resistance (Chang et. al)

Elements for pathogenisisVia enzymes and toxins

Hyaluronidases potentiate infection by attacking ground membranes of connective tissue

Kinases activates plasmin, which prevents blood clotting with fibrinolysis. bacterial diffusion can occur in absence of clotting factors

Hemolysins lyse RBCs

Lipases digest lipids allowing for colonization on skin surfaces and oil glands

PATHO elements cont.Staphylococcal coagulase perhaps contribute to virulence by providing antigenic disguise preventing the recognition of bacterial antigen surfaces

Protein A molecule inhibits phagocytic ingestion

Beta lactamase facilitates survival in face of Abx

Toxins of pathogenesisCytolytic toxins disrupt cell membranes by lysing phagocytes and granules involved in immunological defenses

Exfoliate toxins dissolute desmosomes that bridge skin cells to one another resulting in skin flaking and sloughing

TSS, toxic shock syndrome, toxin causing N/V similar to food poisoning

Panton-Valentine Leukocidin ass. with extreme virulence (e.g. necrotizing pneumonia)

Studying PathologyA Rocky Mountain Lab group suggests that the PVL toxin cannot be causative of extreme virulence

Studies have shown s. aureus infections result in similar presentations with or without the PVL gene (Voyich, et. al, 2006)

Another thought, MSSA has same propensities and molecular mechanisms to cause disease as MRSA, and with developing Abx resistance opportunism for infection occurs when tx fails (Layer, et.al, 2006)

What it looks like

Clinical SignificanceSkin infections include impetigo, folliculitis, carbuncles, styes or boils

Other skin infections include furuncles and abscesses can begin as painful red papules with surrounding erythema and can develop necrotic centers (Dale, Federman 2007)

Clinical Significance cont.More serious problems include penetration beyond cutaneous and soft tissue manifestations

(e.g. pneumonia, deep abscesses, osteomyelitis, endocarditis, phlebitis, mastitis, and/or meningitis, Baron, et. al)

Atypicals include toxic shock syndrome, bacteremia, endocarditis, pneumnoia, osteomyelitis, necrotizing fasciitis

Such disease states are becoming consequence of CA-MRSA infections, no longer limited to hospital settings and very sick populations representative of HA-MRSA

In many of these cases, complications arise with the absence of underlying medical conditions and mortality rates are approaching 64% (Crum, 2004)

Epidmiology

HA MRSA infections have increased from 2% in 1974 to 22% in 1995 (CDC, 2007)

and to 64% in 2004

Each year from the years 2001 to 2003 12 million people were treated for soft tissue infections attributed to s. aureus (CDC, 2007)

Studying the Epi

94,000 acquire invasive MRSA ea year, with a death toll of 19,000 (Klevins, et. al)

Media reports that MRSA kills more than AIDS

9 metropolitan areas were followed for more than a year concluding in a statement that MRSA is a serious problem affecting populations disproportionately

AMA says...MRSA is no longer a problem confined to intensive care units, but a problem affecting 31.8 per 100,000 people

During the course of surveillance 8987 cases of MRSA

58.4% HA, 26.6% CA, 1.3% undetermined (Klevins, et. al)

How to treatTrimethoprim sulfamethoxazole/Bactrim usually a successful DOC

With more severe infections with debridgment or necrosis of soft tissue increased chance of systemic illness--signs to recognize are fever, chills, fatigue, muscle aches, H/A, and/or rash

In such cases of threatened systemic illness, determine the strain type and origin b/c tx is different

TXFor more aggressive CA-MRSA infections tx with Bactrim, doxycycline, minocycline, rifampin,or Zylox for very resistant strains

Tx for active HA-MRSA infections include paraenteral Abx, vancomycin, clindamycin, linelozid, or combo dxs

Additional outpt tx should include keeping nails short and clean, change sleepwear, linens, towels, and wash cloths;

TXMupirocin/Bactroban ointment BID to eliminate nasal carriage

Bleach/water solution for skin colonization BID, twice a week for 15 min

Hibiclens soap

Oral Abx for ten days, followed by rifampin 10mg/kg/dose BID for two days

Tx family members and pets too

In England and Wales

Things I don’t think you’ve heard

New treatments with honey and maggots

Groups are questioning the benefit of circumcision when s.aureus presence in hospitals is increasing

Can MRSA be a sexually transmitted infection?

Streptococcus has historically been causative organism for ‘flesh eating virus’ infections, yet new research shows s.aureus cultured from such wounds

MRSA strains responsible for outbreak type infections in the UK are titled EMRSA 15 and 16 (NIH)

In ConclusionMRSA publications on the rise

No doubt Abx resistance has been problem for years

Now evidence of increased virulence

Evidence of increased incidence, though it is difficult to ascertain true numbers without cohesive federal tracking

No standard/law to report MRSA infections in hospitals. It is not classified as a reportable infection

In ConclusionDO WE KNOW THE TRUTH?

To what degree is the severity? More research needed.

Can we gage the problem accurately? (i.e. hospitals not reporting or under reporting)

Despite varying incidence numbers among population, AMA says it best, I think. Affects populations disproportionately.

Nonetheless, a problem you will encounter. Know how to dx and tx before it is a problem.

Law suits in the UKNumber

• Notification year

• Open claims

• Claims closed with no damages

• Claims settled with damages

• Total claims

• 1999-2000

• 0

• 1

• 1

• 2

• 2000-01

• 0

• 3

• 0

• 3

• 2001-02

• 0

• 2

• 8

• 10

• 2002-03

• 3

• 15

• 24

• 42

• 2003-04

• 4

• 34

• 28

• 66

• 2004-05

• 10

• 47

• 15

• 72

• 2005-06

• 35

• 50

• 12

• 97

• 2006-07

• 90

• 26

• 12

• 128

• 2007-08(1)

• 101

• 5

• 4

• 110

• Total

• 243

• 180

• 107

• 530

• (1) Denotes data to date for current period.

• Source:

• NHS Litigation Authority.

Unsure of need for frenzied plans of action. Sure of need for Education

Otherwise...

Scary Media Propaganda

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