A colorized SEM of MRSA

Methicillin-resistant Staphylococcus aureus was discovered in 1961 in the United Kingdom. It made its first major appearance in the United States in 1981 among intravenous drug users. MRSA is often referred to in the press as a “superbug.”

In 1997, four fatal cases were reported involving children from Minnesota and North Dakota.  Over the next several years, it became clear that CA-MRSA infections were caused by strains of MRSA that differed from the older and better studied health care-associated strains.

The number of MRSA infections in the United States has been increasing significantly. A 2007 report in Emerging Infectious Diseases, a publication of the Centers for Disease Control and Prevention (CDC), estimated the number of MRSA infections in hospitals doubled nationwide, from approximately 127,000 in 1999 to 278,000 in 2005, while at the same time annual deaths increased from 11,000 to more than 17,000.  Another study led by the CDC and published in the October 17, 2007 issue of the Journal of the American Medical Association estimated that MRSA would have been responsible for 94,360 serious infections and associated with 18,650 hospital stay-related deaths in the United States in 2005.  These figures suggest that MRSA infections are responsible for more deaths in the U.S. each year than AIDS.

The Office for National Statistics reported 1,629 MRSA-related deaths in England and Wales during 2005, indicating a MRSA-related mortality rate half the rate of that in the United States for 2005, even though the figures from the British source were explained to be high because of “improved levels of reporting, possibly brought about by the continued high public profile of the disease” during the time of the 2005 United Kingdom General Election. MRSA is thought to have caused 1,652 deaths in 2006 in UK up from 51 in 1993.

It has been argued that the observed increased mortality among MRSA-infected patients may be the result of the increased underlying morbidity of these patients. Several studies, however, including one by Blot and colleagues, that have adjusted for underlying disease still found MRSA bacteremia to have a higher attributable mortality than methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia.

While the statistics suggest a national epidemic growing out of control, it has been difficult to quantify the degree of morbidity and mortality attributable to MRSA. A population-based study of the incidence of MRSA infections in San Francisco during 2004-5 demonstrated that nearly 1 in 300 residents suffered from such an infection in the course of a year and that greater than 85% of these infections occurred outside of the health care setting.  A 2004 study showed that patients in the United States with S. aureus infection had, on average, three times the length of hospital stay (14.3 vs. 4.5 days), incurred three times the total cost ($48,824 vs $14,141), and experienced five times the risk of in-hospital death (11.2% vs 2.3%) than patients without this infection.  In a meta-analysis of 31 studies, Cosgrove et al.,  concluded that MRSA bacteremia is associated with increased mortality as compared with MSSA bacteremia (odds ratio = 1.93; 95% CI = 1.93±0.39).  In addition, Wyllie et al. report a death rate of 34% within 30 days among patients infected with MRSA, a rate similar to the death rate of 27% seen among MSSA-infected patients.

Clinical presentation and concerns

A ruptured MRSA abscess

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.

Treatment

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.  (Methicillin-Sensitive Staphylococcus Aureus)

[What is the antibiotic resistance phenotype of methicilin sensitive staphylococcus aureus (MSSA)?  The phenotype is the expression of the genotype and it is implied in the name- it is sensitive to methicilin vs MRSA which is methicilin resistant staphylococcus aureus.]

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.

On May 18, 2006, a report in Nature identified a new antibiotic, called platensimycin, that had demonstrated successful use against MRSA.

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.

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.

Ocean-dwelling living sponges produce compounds that may make MRSA more susceptible to antibiotics.

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