CA-MRSA An update

Dr.T.V.Rao MD

What Are Staphylococcus aureus?Staphylococcus aureus (S. aureus) is a bacteria normally found on the skin or in the nose of 20 to 30 percent of healthy individuals. When S. aureus is present without causing symptoms, it is called colonization. If symptoms are present, it is called an infection.

What are MRSA?Methicillin-resistant Staphylococcus aureus (MRSA) is a strain of S. aureus that is resistant to methicillin, an antibiotic in the same class as penicillin, and is traditionally seen in people who have been recently hospitalized or who have been treated at a health care facility (such as treatment at a dialysis centre).

What are MRSAMethicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for several difficult-to-treat infections in humans. It is also called oxacillin-resistant Staphylococcus aureus (ORSA). MRSA is any strain of Staphylococcus aureus that has developed, through the process of natural selection, resistance to beta-lactam antibiotics, which include the penicillins (methicillin, dicloxacillin, nafcillin, oxacillin, etc.) and the cephalosporins.

What are MSSAStrains unable to resist these antibiotics are classified as methicillin-sensitive Staphylococcus aureus, or MSSA. The evolution of such resistance does not cause the organism to be more intrinsically virulent than strains of Staphylococcus aureus that have no antibiotic resistance, but resistance does make MRSA infection more difficult to treat with standard types of antibiotics and thus more dangerous.

What is CA-MRSA?

Community-associated MRSA infections (CA-MRSA) are MRSA infections in healthy people who have not been hospitalized or had a medical procedure (such as dialysis or surgery) within the past year.

Staphylococcus aureus are HA- MRSA and CA- MRSA

• S. aureus is most common cause of healthcare-associated infections

• MRSA is the major antibiotic-resistant organism in hospitals; however CA-MRSA increasing

Newer type of MRSA Emerging

Another type of MRSA infection has occurred in the wider community — among healthy people. This form, community-associated MRSA (CA-MRSA), often begins as a painful skin boil. It's spread by skin-to-skin contact. At-risk populations include groups such as high school wrestlers, child care workers and people who live in crowded conditions.

What are the symptoms associated with CA-MRSA

infection?CA-MRSA infections typically begin as skin infections. They first appear as reddened areas on the skin, or can resemble pimples that develop into skin abscesses or boils causing fever, pus, swelling, or pain.

Complications with MRSA

MRSA infections can resist the effects of many common antibiotics, so they are

more difficult to treat. This can allow the infections to spread and sometimes

become life-threatening.

MRSA infections may affect your:

Bloodstream

Lungs Heart

Bones

Joints

Molecular Epidemiology of CA-MRSA

Otter, Lancet ID, 2010

S. aureus acquires resistance to methicillin and its ability to express

different virulence factors

MRSA Colonizes S. aureus most commonly colonizes the anterior nares (the nostrils). The rest of the respiratory tract, open wounds, intravenous catheters, and the urinary tract are also potential sites for infection. Healthy individuals may carry MRSA asymptomatically for periods ranging from a few weeks to many years.

Immune compromised at increased Risk with MRSAPatients with compromised immune systems are at a significantly greater risk of symptomatic secondary infection.

CA-MRSA Epidemiologyneonates, children

homeless, incarcerated, IVDU

MSM, HIV-infected

military personnel

athletes (contact sports)

native aboriginals

household contacts

veterinarians, livestock handlersDavid, Clin Microbiol Rev 2010

Risk factors for CA-MRSA

Participating in contact sports. MRSA can spread easily through cuts and abrasions and skin-to-skin contact.

Living in crowded or unsanitary conditions. Outbreaks of MRSA have occurred in military training camps, child care centres and jails.

Men having sex with men. Homosexual men have a higher risk of developing MRSA infections.

MRSA in Domestic PetsReported in cats, dogs, guinea pigs, parrots

a variety of clones, often HA-MRSA

(Weese, Vet Microbiol 2006;

David, Clin Microbiol Rev 2010)

CA-MRSA as a Cause of Healthcare-Associated Infections

• USA400 post-partum infections, NY mastitis, cellulitis, abscesses (Saiman, CID 2003)

• USA300 prosthetic joint infections, SSIs (Kourbatova, Am J Infect Control 2005; Patel, J Clin Microbiol 2007)

• USA300 accounted for 28% healthcare-associated bacteremias, 20% nosocomomial MRSA BSIs, Atlanta, GA (Seybold, CID 2006)

• USA300 transmission in a Canadian Burn unit (McGuire, SHEA 2007)

CA-MRSA: Enhanced Virulence?

Associated with severe and recurrent SSTI, often in individuals without predisposing risk factors

Associated with necrotizing pneumonia

Appears to be easily transmitted in hospitals, households, and the community

MRSA USA300 Virulence Factors

David, Clin Microbiol Rev 2010

CA-MRSAVirulence

Panton-Valentine Leukocidin (PVL)

-hemolysin (increased expression in CA-MRSA; -hemolysin antibody protective in mouse model) (Wardenburg, Nature Med 2007)

Argenine catabolic mobile element (ACME; unique to CA-MRSA, S. epidermidis; may help strain evade host response and facilitate colonization) (Goering, J Clin Microbiol 2007)

How is it transmitted?

CA-MRSA is spread in the same way as an MRSA infection, mainly through person-to-person contact or contact with a contaminated item such as a towel, clothing or athletic equipment.

How is it transmitted?Bacteria that

exist normally on the skin cause CA-MRSA and so it is possible to infect a pre-existing cut not protected by a dressing or other bandage.

PVL Gene and VirulenceUsing isogenic PVL

knockout mutants in murine models (subcut abscess, pneumonia) has given conflicting results (Voyich, J Infect Dis 2006; Labandeira-Rey, Science 2007)

PVL does appear to contribute to virulence in a rabbit bacteremia model (An Diep, PLoS ONE 2008)

MRSA Impact• Attributable mortality

and morbidity (Whitby, Med J Austr 2001; Cosgrove, Clin Infect Dis 2003)

• Prolonged hospital length of stay (Engemann, Clin Infect Dis 2003; Cosgrove, Infect Control Hosp

Epidemiol 2005)

Antibiotic resistance

MRSA is the result of decades of often unnecessary antibiotic use. For years, antibiotics have been prescribed for colds, flu and other viral infections that don't respond to these drugs. Even when antibiotics are used appropriately, they contribute to the rise of drug-resistant bacteria because they don't destroy every bacteria they target. Bacteria live on an evolutionary fast track, so germs that survive treatment with one antibiotic soon learn to resist others.

What about hVISA?hVISA (heteroresistant): MIC susceptible (< 4 µg/ml), but with a resistant sub-population; detected by PAP-AUC

preliminary step towards development of VISA (Hiramatsu, Lancet ID 2001)

may be associated with treatment failure (Sakoulas, Antimicrob Agents Chemother 2005)

Vancomycin and Treatment Failure

• higher vancomycin MICs associated with worse outcome

• thus: recommendations to use higher vancomycin doses (target trough: 15-20 µg/ml) (Liu, Clin Infect Dis 2011)

• but, higher troughs not associated with better outcome; associated with increased nephrotoxicity (Hidayat, Arch Intern Med 2006)

MRSA Infection Control Strategies

• Contact precautions

• Screening• Decolonization

MRSA DecolonizationDecolonization to prevent staphylococcal SSI (Bode, N Engl J Med 2010)

Observational studies with mupirocin or other agents as part of infection control measures (Hill, J Antimicrob Chemother 1998; Strausbaugh, ICHE 1992; Sandri, ICHE 2006; Ridenour, ICHE 2007; Bowler, ICHE 2010)

Interrupted time-series analysis in 2 UK ICUs: chlorhexidine gluconate baths reduced MRSA transmission, but emergence of strains with reduced susceptibility to CHG (Batra, Clin Infect Dis 2010)

How can the spread of CA-MRSA be controlled?

Careful hand washing is the single most effective way to control the spread of CA-MRSA. Skin infections caused by MRSA should be covered until healed, especially to avoid spreading the infection to others. Family members and others with close contact should wash their hands frequently with soap and water. Personal items that may be contaminated (towels, razors, clothing, etc.) should not be shared

Preventing CA-MRSA

Wash your hands. Careful hand-washing remains your best defence against germs. Scrub hands briskly for at least 15 seconds, then dry them with a disposable towel and use another towel to turn off the faucet.

Keep wounds covered.Keep cuts and

abrasions clean and covered with sterile, dry bandages until they heal. The pus from infected sores may contain MRSA, and keeping wounds covered will help keep the bacteria from spreading.

Keep personal items personal.

Avoid sharing personal items such as towels, sheets, razors, clothing and athletic equipment. MRSA spreads on contaminated objects as well as through direct contact.

Shower after athletic games or practices

Shower immediately after each game or practice. Use soap and water. Don't share towels.

Sanitize linens If you have a cut or sore, wash towels and bed linens in a washing machine set to the hottest water setting (with added bleach, if possible) and dry them in a hot dryer. Wash gym and athletic clothes after each wearing.

How can the spread of CA-MRSA be controlled?

Both the Centres for Disease Control and Prevention (CDC) and the National Collegiate Athletic Association (NCAA) have issued recommendations for preventing the spread of MRSA among athletes. These include practicing good personal hygiene, including showering after practices and competitions and not sharing personal items such as towels

How can the spread of CA-MRSA be Controlled?

Athletes who participate in sports where equipment is often collectively used are encouraged to reduce sharing as much as possible and to regularly wipe-down equipment/mats with commercial disinfectants or a 1:100 solution of diluted bleach (one tablespoon bleach in one quart water).

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