Methicillin resistant Staphylococcus aureus (MRSA)

Common nosocomial isolate and accounts for more than 50% of Staph aureus isolates in ICU’s in the U.S.

Estimated by the CDC 18,650 deaths in the U.S. in 2005.

In 2017 there was an estimated 120,000 cases of staphylococcal aureus bacteremia resulting in 20,000 deaths.

Currently MRSA infections estimated to affect approximately 80,000 hospitalizations and causes 11,000 related deaths in the US each year.

Hospitals are the primary reservoir and hospital contact accounts for most cases of MRSA infections in the community.

Methicillin-resistant Staphylococcus aureus is found in approximately 50% of isolates in acute care hospitals in the United States.

It is the most common cause of skin, soft tissue, and procedure related infections.

Rates of invasive MRSA infections are highest within six months after hospital discharge and do not normalize for one year.

Screening usually involve the anterior nares, but one fourth of carriers are colonized only in the throat.

About 2% of the general population are methicillin-resistant staphylococcal aureus (MRSA) carriers.

MRSA carriers have a higher risk of infection and post discharge re-hospitalization.

CLEAR trial of use of topical decolonization with chlorine icing and muciprocin in MRSA carriers leads to lower risk of infections and readmissions than hygiene educational alone.

Throat carriers usually have absence of exposure to the health care system and are of younger age than those who are nares carriers.

Taking swabs only from the anterior nares and not from the throat will result in limited success to control MRSA by hospital screening.

Increasing emergence of community acquired isolates.

Majority of MRSA infections involve skin and soft tissues, and a minority are invasive and life-threatening.

Compared with a patient with methicillin susceptible staphylococcal infection, a patient with MRSA has a higher all- cause mortality rate, bacteria associated mortality, longer hospital stay, and a 2 fold higher risk of being discharged to a skilled nursing facility.

Overall incidence of invasive disease is declining (Dante’s R et al).

Incidence of health care associated and hospital associated invasive MRSA have declined.

Healthcare related disease associated with invasive infection, healthcare exposure, and multidrug resistance.

Community acquired disease mainly in young and healthy patients with no recent healthcare exposure, with strains of generally sensitive to non-ß-lactam antibiotics.

Community associated MRSA strains account for more than half of all noninvasive MRSA infections.

A CDC study showed that nearly 80% of the total number of cases of invasive MRSA infections during the study in 2011 were in the community setting, which included both community acquired infections and healthcare associated outpatient infections.

In the above study the overall rate of invasive M RSA infections decreased, but the decrease was evident mostly in healthcare settings and much less so in the community setting.

In the above steady there was a higher proportion of people with intravenous drug use, HIV, and smoking history with the community acquired MRSA.

Health care associated MRSA generally in older patients with comorbidities.

Community associated MRSA strains are frequently susceptible to gentamicin, tetracyclines, lincosamides, and trimethoprim sulfamethoxazole.

Many community associated MR SA infections are limited to superficial skin and skin structure infections.

Individuals living near high-density farms or near crop fields using manure from high- density livestock farms are at increased risk of developing MRSA soft tissue infections.

Community associated MR SA disease can cause severe systemic infections, including pneumonia and blood stream infections.

More than 10% of sepsis infections in hospitals due to such infections.

Sepsis in patients with MRSA associated with a worse outlook than in patients with methicillin sensitive S aureus sepsis.

Community acquired infections can cause wide range of disease processes, it most commonly is associated with skin and soft tissue infections: including-furunculosis, impetigo, cellulitis, abscesses and pustulosis.

Approximately 50% of community acquired infections occur among injection drug users.

Skin infections have a tendency to recur and can occur in close contacts of such patients.

Community outbreaks have occurred in groups of athletes, military recruits, inmates at correctional facilities and in religious communities.

Central line bloodstream infections have declined in incidence in recent years in all major ICU types and has remained stable in pediatric ICU’s suggesting prevention efforts are succeeding (Burton).

Resistant to all beta-lactam antibiotics.

Resistance is mediated by a chromosomally incorporated resistance gene, mecA, which causes the altered binding of beta-lactams to penicillin binding protein 2a.

Treatment of MRSA infection with first line beta-lactam antibiotics is ineffective but also maybe harmful as it activates a gene mecA which in turn activates a back up pathway for cell wall synthesis that can trigger an inflammatory response.

Isolates that have oxacillin minimum inhibitory concentration of >2 micrg/mL or harbor the mecA gene.

Isolates are preferably identified by detecting the mecA gene or its protein product, PBP2a.

Majority of community associated MRSA skin and soft tissue infections in the U.S. caused by single pulsed field type isolates, USA 300, which are typically resistant to beta lactam and macrolide antibiotics and contain genes for the PVL toxin, which lyses white blood cells.

USA300 clone has been responsible for the majority of community and health care associated outbreaks since the 1990s.

6% of community acquired MRSA infections are invasive (Fridkin) and in a pediatric study 9% of children hospitalized with this process had invasive disease (Bancroft).

MRSA intervention programs with the use of intranasal mupirocin and patients colonized with MRSA receiving vancomycin prophylaxis has resulted in a near complete elimination of MRSA surgical site wound infections after cardiac surgery (Walsh EE et al).

USA300 clone and USA400 variant are the predominant causes of community associated S aureus skin and soft tissue infections and empirical use of agents active against community associated MRSA (Vancomycin or trimethoprin-sulfamethoxazole management is warranted in serious skin and soft tissue infections (King).

USA300 isolates carry the Pantonn-Valentine leukocidin genesin the arginine catabolic mobile element.

USA300 isolates have increasingly develop resistance to antibiotics including: clindamycin quinolones, tetracyclines, mupirocin, vancomycin and daptomycin. macrolides.

MRSA organisms have the capability to form abscesses.

MRSA commonly causes soft tissue injections including furuncles, abscesses and purulent cellulitis.

MRSA may be associated with pneumonia, especially with prior recent influenza infection, endovascular infections, and osteomyelitis.

MRSA associated with wound and postoperative infections, prosthetic joint infections, endovascular infections, catheter associated blood stream infections, and healthcare associated pneumonias.

Initially low level resistance to Vancomycin associated with increased thickness of bacterial cell walls.

Low level resistance designated VISA or GISA for Vancomycin or glycopeptide intermediate resistant S aureus.

High level resistance to Vancomycin (VRSA) is due to the acquisition of vanA gene cluster.

While there are few strains of VRSA such strains are also resistant to clindamycin, aminoglycosides, trimethoprin-sulfamethoxazole, and fluoroquinolones.

Infection with multiorgan resistant USA300 MRSA common among men having sex with men.

Strains of healthcare associated MRSA do not typically contain genes for the PVL toxin.

Precautions to disinfect all ICU patients as if they had methicillin-resistant Staphylococcus aureus (MRSA) cut infections substantially more than other more targeted strategies: that is universal decolonization reduced the likelihood of MRSA infection in the ICU by 37% and brings down the risk of any bloodstream infection by 44% (Huang, SS et al).

In the above study the number of patients needed to treat to prevent one bloodstream infection was 54.

MRSA Bacteremia is associated with mortality of more than 20%.
Screening and then isolating MRSA-colonized patients was found to be the least effective option among the three tested in the trial and had almost no impact on the prevalence of MRSA or blood stream infection.

Isolating patients with MRSA does not necessarily result in fewer infections since most MRSA infections are endogenous, meaning the infectious strain colonized the patient for sometime prior to infection, and contact precautions do not prevent infections in already colonized patients.

Contact precautions prevent MRSA acquisition by patients who are non carriers.

MRSA acquisition events are uncommon at approximately 2% of higher risk patients in an ICU, and only 20% of apparent acquisitions are attributed to patient-patient transmission.

Targeted decolonization with chlorhexidine baths and nasal mupirocin (Bactroban) has an intermediate impact on effectiveness.

Across-the-board decolonization benefit patients by cutting down on contact precautions.

Universal decolonization involves a 5-day regimen of twice-daily intranasal mupirocin and daily bathing with chlorhexidine cloths during the ICU stay.

Current standard therapy for MRSA bacteremia is vancomycin or daptomycin.

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