MRSA

 

by Alan Pontious

 

·         Disease name, means of transmission and usual reservoirs

      Methicillin-resistant Staphylococcus aureus (MRSA) is transmitted by skin-to-skin contact. (1)

      Usual reservoirs for MRSA in hospital and institutions are staff, patients, and inanimate objects such as beds, linen, and utensils.  By far, the most important reservoir is patients who may be colonized with MRSA without evidence of infection. (2)

·         Etiologic agent, its general characteristics and key tests for identification (be specific for this microbe!)

      MRSA is, itself, the etiological agent for MRSA (staph) infection. (3)

The general characteristics of MRSA infections are the same as that of (methicillin-susceptible) Staphylococcus aureus infections.

The organism is a gram-positive coccus (0.7 - 1.2 µm), usually in clusters, pyogenic (pus-eliciting), "tissue" invasive, produces purulent (pus-filled) lesions, is an extracellular pathogen (destroyed within leukocytes), non-motile, non spore-forming, causes acute illnesses, is facultatively anaerobic, its peptidoglycan are distinguished by the pentaglycine cross-bridge, its colonies are often surrounded by a clear zone of hemolysis (beta hemolysis) due to production of hemolysins, it can withstand heat at 60°C for 30 min. It will grow in media containing 7.5% to 10% NaCl, it can remain viable for months on agar plates stored at 4°C, it can grow at 6.5°C to 46°C, grows at pH 4.2 - 9.3. (4)

To diagnose S. aureus, a sample is obtained from the infection site and sent to a microbiology laboratory for testing. If S. aureus is found, the organism should be further tested to determine which antibiotic would be effective for treatment.

Doctors often diagnose MRSA by checking a tissue sample or nasal secretions for signs of drug-resistant bacteria. Current diagnostic procedures involve sending a sample to a lab where it is placed in a dish of nutrients that encourage a culture. The tests involve subjecting it to the physical and chemical environments with the aforementioned characteristics. It takes about 48 hours for the bacteria to grow. (5)

The term methicillin resistant is historically used to describe resistance to any of this class of antimicrobials. (6) After cultures have been grown, they will be exposed to these antimicrobials to discern S. aureus from MRSA. However, newer tests that can detect staph DNA in a matter of hours are now becoming more widely available. This will help healthcare providers decide on the proper treatment regimen for a patient more quickly, after an official diagnosis has been made. (5)

·         Historical information to include when and who isolated the microbe and any significance of its name

The S. aureus bacterium, commonly known as staph, was discovered in the 1880s. During this era, S. aureus infection commonly caused painful skin and soft tissue conditions such as boils, scalded-skin syndrome, and impetigo. More serious forms of S. aureus infection can progress to bacterial pneumonia and bacteria in the bloodstream—both of which can be fatal. S. aureus acquired from improperly prepared or stored food can also cause a form of food poisoning

In the 1940s, medical treatment for S. aureus infections became routine and successful with the discovery and introduction of antibiotic medication, such as penicillin.

From that point on, however, use of antibiotics—including misuse and overuse—has aided natural bacterial evolution by helping the microbes become resistant to drugs designed to help fight these infections.  In the late 1940s and throughout the 1950s, S. aureus developed resistance to penicillin. Methicillin, a form of penicillin, was introduced to counter the increasing problem of penicillin-resistant S. aureus. Methicillin was one of most common types of antibiotics used to treat S. aureus infections; but, in 1961, British scientists identified the first strains of S. aureus bacteria that resisted methicillin. This was the so-called birth of MRSA.

The first reported human case of MRSA in the United States came in 1968. Subsequently, new strains of bacteria have developed that can now resist previously effective drugs, such as methicillin and most related antibiotics.

MRSA is actually resistant to an entire class of penicillin-like antibiotics called beta-lactams. This class of antibiotics includes penicillin, amoxicillin, oxacillin, methicillin, and others.

S. aureus is evolving even more and has begun to show resistance to additional antibiotics. In 2002, physicians in the United States documented the first S. aureus strains resistant to the antibiotic, vancomycin, which had been one of a handful of antibiotics of last resort for use against S. aureus. Though it is feared that this could quickly become a major issue in antibiotic resistance, thus far, vancomycin-resistant strains are still rare at this time. (7)

·        Signs and symptoms of the disease

Severe Infections

MRSA in healthcare settings usually causes more severe and potentially life-threatening infections, such as bloodstream infections, surgical site infections, or pneumonia. The signs and symptoms will vary by the type and stage of the infection.

Skin Infections

In the community, most MRSA infections are skin infections that may appear as pustules or boils which often are red, swollen, painful, or have pus or other drainage. They often first look like spider bites or bumps that are red, swollen, and painful. These skin infections commonly occur at sites of visible skin trauma, such as cuts and abrasions, and areas of the body covered by hair (e.g., back of neck, groin, buttock, armpit, beard area of men).  (8)

MRSA image 003
Photo from
http://www.cdc.gov/mrsa/mrsa_initiative/skin_infection/mrsa_photo_003.html

·         Microbial virulence mechanisms contributing to the disease process

S. aureus strains can express a wide array of potential virulence factors, including surface proteins that promote adherence to damaged tissue, bind proteins in blood to help evade antibody-mediated immune responses, and promote iron uptake. The organism also expresses a number of membrane-damaging toxins and superantigen toxins that can cause tissue damage and the symptoms of septic shock, respectively. There is a growing realization that S. aureus has multiple mechanisms for evading both innate immunity mediated by polymorphonuclear leukocytes and induced immunity mediated by both B and T cells. Some virulence factors are expressed by genes that are located on mobile genetic elements called pathogenicity islands (e.g., toxic shock syndrome toxin–1 and some enterotoxins) or lysogenic bacteriophages (e.g., Panton-Valentine leucocidin [PVL]) and factors associated with suppressing innate immunity such as the chemotaxis inhibitory protein and staphylokinase, which are integrated in the bacterial chromosome. (9)

·         Control or treatment for the disease

As stated by the U.S. Centers for Disease Control and Prevention (CDC):

·         "First-line treatment for mild abscesses is incision and drainage."

·         "If antibiotic treatment is clinically indicated, it should be guided by the susceptibility profile of the organism." When the tests are run to determine that the Staph bacteria isolated from a given patient are methicillin resistant, these tests also provide information about which antibiotics can successfully kill the bacteria (its susceptibility profile)."

Fortunately, most MRSA still can be treated by certain specific antibiotics (for example, vancomycin [Vancocin], linezolid [Zyvox], and others, often in combination with vancomycin). Most moderate to severe infections need to be treated by intravenous antibiotics, usually given in the hospital setting. Some CA-MRSA strains are susceptible to trimethoprim-sulfamethoxazole (Bactrim) doxycycline (Vibramycin), and clindamycin (Cleocin); although reports suggest clindamycin resistance is increasing rapidly. In addition, some strains are now resistant to vancomycin. (10)

·         Current outbreaks or cases, both globally and locally (include incidence figures for each)

The estimated number of people developing a serious MRSA infection (i.e., invasive) in 2005 was about 94,360; this is higher than estimates using other methods.

Approximately 18,650 persons died during a hospital stay related to these serious MRSA infections.

Serious MRSA disease is still predominantly related to exposures to healthcare delivery:

·         About 85% of all invasive MRSA infections were associated with healthcare, and of those, about two-thirds occurred outside of the hospital, while about one third occurred during hospitalization.

·         About 14% of all the infections occurred in persons without obvious exposures to healthcare.

Although the rates of disease varied between the geographically diverse sites participating in the surveillance, overall rates of disease were consistently highest among older persons (age >65), Blacks, and males.

Evaluation of the pathogens causing these infections confirmed that most of the strains associated with these serious MRSA infections were caused by strains traditionally associated with healthcare. However, the strains traditionally associated with transmission in the community are now being identified in healthcare. (11)

http://www.cddep.org/sites/cddep.org/files/ETCfig1-4.gif
photo from
http://www.cddep.org/sites/cddep.org/files/ETCfig1-4.gif

·         Prevention, particularly current research about a vaccine or other means of control/prevention

A good medical practice is to determine, by microbiological techniques done in a lab, which antibiotic(s) can kill the MRSA and use it alone or, more often, in combination with additional antibiotics to treat the infected patient. Since resistance can change quickly, antibiotic treatments may need to change also. Many people think they are "cured" after a few antibiotic doses and stop taking the medicine. This is a bad decision because the MRSA may still be viable in or on the person and thus is capable of reinfecting the person. Also, the surviving MRSA may be exposed to low antibiotic doses when the medicine is stopped too soon; this low dose may allow MRSA enough time to become resistant to the medicine. Consequently, MRSA patients (in fact, all patients) treated with appropriate antibiotics should take the entire course of the antibiotic as directed by their doctor. A note of caution is that, in the last few years, there have been reports of a new strain of MRSA that is resistant to vancomycin (VRSA or vancomycin-resistant S. aureus) and other antibiotics. Currently, VRSA is detected more often than a few years ago, but if it becomes widespread, it may be the next "superbug." (10)         

A protein-polysaccharide conjugate vaccine has been developed and has shown promise for preventing the most serious infections in one high risk group, dialysis patients. However this has not been tested in otherwise healthy persons. This vaccine has not been approved by the FDA and approval will require further evidence of effectiveness. (12)

References

(1)  http://www.mayoclinic.com/health/mrsa/DS00735

(2)  http://dermnetnz.mobify.me/bacterial/methicillin-resistance.html

(3)  http://medscape.com/viewarticle/718531

(4)  http://www.channing.harvard.edu/4a.htm

(5)  http://www.niaid.nih.gov/topics/antimicrobialResistance/Examples/mrsa/Pages/diagnosis.aspx

(6)   http://www.rapidmicrobiology.com/test-methods/MRSA.php

(7)  http://www.niaid.nih.gov/topics/antimicrobialResistance/Examples/mrsa/Pages/history.aspx

(8)  http://www.cdc.gov/mrsa/symptoms/index.html

(9)  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC535074/

(10)  http://www.medicinenet.com/mrsa_infection/page6.htm       

(11)  http://www.cdc.gov/mrsa/library/index.html

(12)  http://www.cdc.gov/ncidod/aip/research/mrsa.html#mrsa_prevention