Methicillin-resistant Staphylococcus aureus (MRSA)
Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for several difficult-to-treat infections in humans. It may also be referred to as multidrug-resistant Staphylococcus aureus or oxacillin-resistant Staphylococcus aureus (ORSA) or simply "Staph." MRSA is by definition any strain of Staphylococcus aureus bacteria that is resistant to a large group of antibiotics called the beta-lactams, which include the penicillins and the cephalosporins.
MRSA has adapted to survive treatment with beta-lactam antibiotics, including methicillin, dicloxacillin, nafcillin, and oxacillin. MRSA is especially troublesome in hospital-associated (nosocomial) infections. In hospitals, patients with open wounds, invasive devices, and weakened immune systems are at greater risk for infection than the general public. Hospital staff who do not follow proper sanitary procedures may transfer bacteria from patient to patient. Visitors to patients with MRSA infections or MRSA colonization are advised to follow hospital isolation protocol by using gloves, gowns, and masks when indicated. Visitors, including health care providers, who do not follow such protocols are capable of spreading the bacteria to areas such as cafeterias, bathrooms, elevators, or various other surfaces.
MRSA is often sub-categorized as community-acquired MRSA (CA-MRSA) or health care-associated MRSA (HA-MRSA) although this distinction is complex. Some have defined CA-MRSA by characteristics of patients who develop an MRSA infection while other authors have defined CA-MRSA by genetic characteristics of the bacteria themselves. The first reported cases of community-acquired MRSA began to appear in the mid-1990s from Australia, New Zealand, the United States, the United Kingdom, France, Finland, Canada, and Samoa, notable because they involved people who had not been exposed to a health-care setting. The new CA-MRSA strains have rapidly become the most common cause of cultured skin infections among individuals seeking emergency medical care in urban areas of the United States. These strains also commonly cause skin infections in athletes, prisoners and soldiers. However, in a 2002 report about CRSA, many cases were children who required hospitalization. MRSA kills about 18,000 Americans annually.
Clinical presentation and concerns
S. aureus most commonly colonizes the anterior nares (the nostrils), although the respiratory tract, opened wounds, intravenous catheters, and urinary tract are also potential sites for infection. Healthy individuals may carry MRSA asymptomatically for periods ranging from a few weeks to many years. Patients with compromised immune systems are at a significantly greater risk of symptomatic secondary infection.
MRSA can be detected by swabbing the nostrils of patients and isolating the bacteria found inside. Combined with extra sanitary measures for those in contact with infected patients, screening patients admitted to hospitals has been found to be effective in minimizing the spread of MRSA in hospitals in the United States, Denmark, Finland, and the Netherlands.
MRSA progresses substantially within 24–48 hours of initial topical symptoms. After 72 hours, MRSA can take hold in human tissues and become resistant to treatment. The initial presentation of MRSA is small red bumps that resemble pimples, spider bites, or boils that may be accompanied by fever and occasionally rashes. Within a few days the bumps become larger, more painful, and eventually open into deep, pus-filled boils. About 75 percent of CA-MRSA infections are localized to skin and soft tissue and usually can be treated effectively. However CA-MRSA strains display enhanced virulence, spreading more rapidly and causing illness much more severe than traditional HA-MRSA infections, and they can affect vital organs and lead to widespread infection (sepsis), toxic shock syndrome and necrotizing ("flesh-eating") pneumonia. This is thought to be due to toxins carried by CA-MRSA strains, such as PVL and PSM, though PVL was recently found to not be a factor in a study by the National Institute of Allergy and Infectious Diseases (NIAID) at the NIH. It is not known why some healthy people develop CA-MRSA skin infections that are treatable whereas others infected with the same strain develop severe infections or die.
The most common manifestations of CA-MRSA are skin infections such as necrotizing fasciitis or pyomyositis (most commonly found in the tropics), necrotizing pneumonia, infective endocarditis (which affects the valves of the heart), or bone or joint infections. CA-MRSA often results in abscess formation that requires incision and drainage. Before the spread of MRSA into the community, abscesses were not considered contagious because it was assumed that infection required violation of skin integrity and the introduction of staphylococci from normal skin colonization. However, newly emerging CA-MRSA is transmissible (similar, but with very important differences) from Hospital-Associated MRSA. CA-MRSA is less likely than other forms of MRSA to cause cellulitis.
Both CA-MRSA and HA-MRSA are resistant to traditional anti-staphylococcal beta-lactam antibiotics, such as cephalexin. CA-MRSA has a greater spectrum of antimicrobial susceptibility, including to sulfa drugs (like co-trimoxazole/trimethoprim-sulfamethoxazole), tetracyclines (like doxycycline and minocycline) and clindamycin, but the drug of choice for treating CA-MRSA has not been established. HA-MRSA is resistant even to these antibiotics and often is susceptible only to vancomycin. Newer drugs, such as linezolid (belonging to the newer oxazolidinones class), may be effective against both CA-MRSA and HA-MRSA.
Vancomycin and teicoplanin are glycopeptide antibiotics used to treat MRSA infections. Teicoplanin is a structural congener of vancomycin that has a similar activity spectrum but a longer half-life. Because the oral absorption of vancomycin and teicoplanin is very low, these agents must be administered intravenously to control systemic infections. Treatment of MRSA infection with vancomycin can be complicated, due to its inconvenient route of administration. Moreover, many clinicians believe that the efficacy of vancomycin against MRSA is inferior to that of anti-staphylococcal beta-lactam antibiotics against MSSA.
Several newly discovered strains of MRSA show antibiotic resistance even to vancomycin and teicoplanin. These new evolutions of the MRSA bacterium have been dubbed Vancomycin intermediate-resistant Staphylococcus aureus (VISA). Linezolid, quinupristin/dalfopristin, daptomycin, and tigecycline are used to treat more severe infections that do not respond to glycopeptides such as vancomycin.
Treatments in clinical trials
It has been reported that maggot therapy to clean out necrotic tissue of MRSA infection has been successful. Studies in diabetic patients reported significantly shorter treatment times than those achieved with standard treatments.
Many antibiotics against MRSA are in phase II and phase III clinical trials. eg:
Phase III : ceftobiprole, Ceftaroline, Dalbavancin, Telavancin, Aurograb, torezolid, iclaprim…
Phase II : nemonoxacin.
An entirely different and promising approach is phage therapy (e.g., at the Eliava Institute in Georgia), which in mice had a reported efficacy against up to 95% of tested Staphylococcus isolates.
On May 18, 2006, a report in Nature identified a new antibiotic, called platensimycin, that had demonstrated successful use against MRSA.
Ocean-dwelling living sponges produce compounds that may make MRSA more susceptible to antibiotics.
At risk populations include:
- People with weak immune systems (people living with HIV/AIDS, cancer patients, transplant recipients, severe asthmatics, etc.)
- Intravenous drug users
- Use of quinolone antibiotics
- Young children
- The elderly
- College students living in dormitories
- Persons staying or working in a health care facility for an extended period of time
- People who spend time in coastal waters where MRSA is present, such as some beaches in Florida and the west coast of the United States
- People who spend time in confined spaces with other people, including prison inmates, soldiers in basic training, and individuals who spend considerable time in changing rooms or gyms
MRSA infections occur mostly in hospitals and healthcare facilities, with a higher incident rate in nursing homes or long-term care facilities. Rates of MRSA infection are also increased in hospitalised patients who are treated with quinolones. Healthcare provider to patient transfer is common, especially when healthcare providers move from patient to patient without performing necessary handwashing techniques between patients. However, it should be noted that MRSA can cause infections outside of hospitals as well.
In one hospital in Texas 12% of staff were carriers of MRSA; it was found that 15% of the staff in an Illinois emergency room were carriers.
In confined environments such as prisons, with continual admission of new members who may typically be in poor health and adopt poor hygiene practices, there have been a number of challenges reported first in the U.S. and then in Canada. The earliest reports were made by the CDC in state prisons. Subsequently reports of a massive rise in skin and soft tissue infections were reported by the CDC in the Los Angeles County Jail system in 2001, and this has continued. Pan et al. reported on the changing epidemiology of MRSA skin infection in the San Francisco County Jail, noting the MRSA accounted for >70% of S. aureus infection in the jail by 2002. Lowy and colleagues reported on frequent MRSA skin infections in New York State Prisons. Two reports on inmates in Maryland have demonstrated frequent colonization with MRSA.
In the news media hundreds of reports of MRSA outbreaks in prisons appeared between 2000 and 2008. For example, in February 2008, The Tulsa County Jail in the U.S. State of Oklahoma started treating an average of twelve Staphylococcus cases per month. A report on skin and soft tissue infections in the Cook County Jail in Chicago in 2004-5 demonstrated that MRSA was the most common cause of these infections among cultured lesions and furthermore that few risk factors were more strongly associated with MRSA infections than infections caused by methicillin-susceptible S. aureus. In response to these and many other reports on MRSA infections among incarcerated and recently incarcerated persons, the Federal Bureau of Prisons has released guidelines for the management and control of the infections although few studies provide an evidence base for these guidelines.
People in contact with live food-producing animals
Cases of MRSA have increased in livestock animals. CC398 is a new clone of MRSA that has emerged in animals and is found in intensively reared production animals (primarily pigs, but also cattle and poultry), where it can be transmitted to humans. Although being dangerous to humans CC398 is often asymptomatic in food-producing animals.
In the United States, there have been increasing numbers of reports of outbreaks of MRSA colonization and infection through skin contact in locker rooms and gyms, even among healthy populations. A study published in the New England Journal of Medicine linked MRSA to the abrasions caused by artificial turf. Three studies by the Texas State Department of Health found that the infection rate among football players was 16 times the national average. In October 2006, a high school football player was temporarily paralyzed from MRSA-infected turf burns. His infection returned in January 2007 and required three surgeries to remove infected tissue, as well as three weeks of hospital stay. MRSA has also been found in the public school systems throughout the country.
MRSA is also becoming a problem in pediatric settings, including hospital nurseries. A 2007 study found that 4.6% of patients in U.S. health care facilities were infected or colonized with MRSA.
Prevention and infection-control strategies
Patient screening upon hospital admission, with nasal cultures, prevents the cohabitation of MRSA carriers with non-carriers, and exposure to infected surfaces. The test used (whether a rapid molecular method or traditional culture) is not as important as the implementation of active screening. In the United States and Canada, the Centers for Disease Control and Prevention issued guidelines on October 19, 2006, citing the need for additional research, but declined to recommend such screening.
In some UK hospitals screening for MRSA is performed in every patient and all NHS surgical patients, except for minor surgeries, are previous checked for MRSA.
In a US cohort of 1300 healthy children, 2.4% carried MRSA in their nose.
Alcohol has been proven to be an effective surface sanitizer against MRSA. Quaternary ammonium can be used in conjunction with alcohol to extend the longevity of the sanitizing action. The prevention of nosocomial infections involves routine and terminal cleaning. Non-flammable Alcohol Vapor in Carbon Dioxide systems (NAV-CO2) do not corrode metals or plastics used in medical environments and do not contribute to antibacterial resistance.
In healthcare environments, MRSA can survive on surfaces and fabrics, including privacy curtains or garments worn by care providers. Complete surface sanitation is necessary to eliminate MRSA in areas where patients are recovering from invasive procedures. Testing patients for MRSA upon admission, isolating MRSA-positive patients, decolonization of MRSA-positive patients, and terminal cleaning of patients' rooms and all other clinical areas they occupy is the current best practice protocol for nosocomial MRSA.
At the end of August 2004, after a successful pilot scheme to tackle MRSA, the UK National Health Service announced its Clean Your Hands campaign. Wards were required to ensure that alcohol-based hand rubs are placed near all beds so that staff can hand wash more regularly. It is thought that even if this cuts infection by no more than 1%, the plan will pay for itself many times over.
As with some other bacteria, MRSA is acquiring more resistance to some disinfectants and antiseptics. Although alcohol-based rubs remain somewhat effective, a more effective strategy is to wash hands with running water and an anti-microbial cleanser with persistent killing action, such as Chlorhexidine
A June 2008 report, centered on a survey by the Association for Professionals in Infection Control and Epidemiology, concluded that poor hygiene habits remain the principal barrier to significant reductions in the spread of MRSA.
Essential oil diffusion
An in vitro study on the inhibition of MRSA by essential oil diffusion found that 72 of 91 investigated essential oils exhibited zones of inhibition in soy agar plates streaked with MRSA (strain ATCC 700699). The most effective being lemongrass oil (Cymbopogon flexuosus), lemon myrtle oil (Backhousia citriodora), mountain savory oil (Satureja montana), cinnamon oil (Cinnamomum verum), and melissa oil (Melissa officinalis) essential oils. Of these, lemongrass essential oil was the most effective, completely inhibiting all MRSA colony growth.
Tea tree oil also kills all MRSA strains that have been tested.
After the drainage of boils or other treatment for MRSA, patients can shower at home using chlorhexidine (Hibiclens) or hexachlorophene (Phisohex) antiseptic soap from head to toe, and apply mupirocin (Bactroban) 2% ointment inside each nostril twice daily for 7 days, using a cotton-tipped swab. Household members are recommended to follow the same decolonization protocol.
Doctors may also prescribe antibiotics such as clindamycin, doxycycline or trimethoprim/sulfamethoxazole. However, there is very little evidence that using more antibiotics actually has the effect of preventing recurrent MRSA skin infections.
Proper disposal of hospital gowns
Used paper hospital gowns are associated with MRSA hospital infections, which could be avoided by proper disposal.
Current US guidance does not require workers in the general workplace (excluding medical facilities) with MRSA infections to be routinely excluded from going to work. Therefore, unless directed by a health care provider, exclusion from work should be reserved for those with wound drainage that cannot be covered and contained with a clean, dry bandage and for those who cannot maintain good hygiene practices. Workers with active infections should be excluded from activities where skin-to-skin contact is likely to occur until their infections are healed. Health care workers should follow the Centers for Disease Control and Prevention's Guidelines for Infection Control in Health Care Personnel.
To prevent the spread of staph or MRSA in the workplace, employers should ensure the availability of adequate facilities and supplies that encourage workers to practice good hygiene; that surface sanitizing in the workplace is followed; and that contaminated equipment are sanitized with Environmental Protection Agency (EPA)-registered disinfectants.
Restricting antibiotic use
Glycopeptides, cephalosporins and in particular quinolones are associated with an increased risk of colonisation of MRSA. Reducing use of antibiotic classes which promote MRSA colonisation, especially fluoroquinolones is recommended in current guidelines.