Introduction

MRSA is the abbreviation for methicillin-resistant Staphylococcus aureus. Staphylococcus is a group of bacteria, familiarly known as Staph (pronounced "staff"), that can cause a multitude of diseases as a result of infection of various tissues of the body. Distribution of S. aureus is worldwide: As many as 11%-40% of the population is estimated to be colonized. However, in 1959, methicillin, an antibiotic closely related to penicillin, was introduced to treat Staphylococcus and other bacterial infections. Within one to two years, Staphylococcus aureus bacteria (S. aureus) started to be isolated that were resistant to methicillin. These S. aureus bacteria were then termed methicillin-resistant. MRSA usually show resistance to many antibiotics. Methicillin-resistant Staphylococcus Aureus (MRSA) is a type of staph bacteria that is resistant to certain antibiotics called beta-lactams. These antibiotics include methicillin and other more common antibiotics such as oxacillin, penicillin, and amoxicillin. In the community, most MRSA infections are skin infections. More severe or potentially life-threatening MRSA infections occur most frequently among patients in healthcare settings. While 25% to 30% of people are colonized in the nose with staph, less than 2% are colonized with MRSA. Because MRSA is so antibiotic resistant, it is termed a "superbug" by some investigators. This superbug is a variation of an already recognized human pathogen, S. aureus, gram-positive bacteria that occur in grape-like clusters termed cocci. The bacteria are usually found in the human armpit, groin, nose (most frequently), and throat.

Figure 1 : Shows the microscopic image of MRSA (Methicillin Resisstant Staphylococcus Aureus ).

Literature Review.
Causes of MRSA. Plasmids, genetic elements that can be transferred from one bacterium to another, cause S. aureus to develop resistance to antibiotics. At least five types of genetic material (SCCmec genes I-V) have been identified. Hospital-acquired MRSA (HA-MRSA) usually have genes I-III while community-acquired MRSA (CA-MRSA) have genes IV-V. HA-MRSA is resistant to more antibiotics than CA-MRSA. These plasmids are strands of DNA, separate from the bacterial genome, which can self-replicate and frequently are responsible for the synthesis of compounds that cause antibiotic resistance in bacteria. MRSA bacteria can be transmitted by direct (though skin and body fluids) and indirect contact (from towels, diapers, and toys) to uninfected people. Also, some individuals have MRSA on their body (on their skin or in their nose or throat) but show no symptoms of infection; these people are termed MRSA carriers (see above) and can transmit MRSA to others. Statistics show that CA-MRSA is the predominant MRSA type found in the population. Most carriers are best detected by culturing MRSA from nasal swabs.

Hospital-Associated MRSA and Community-Associated MRSA The cartoon above illustrates the difference between hospital-associated (HA) and community-associated (CA) MRSA. The methicillin-resistance gene (mecA) can be passed from one bacterial cell to another as a transposable element (a piece of DNA that inserts itself into the bacterial chromosome). The pvl gene is normally present in the genome of the S. aureus bacteriophage and encodes a toxin known as the PVL protein. Upon infection, the phage can insert its DNA into the bacterial chromosome transforming a non-toxic bacterial cell into a bacterium capable of producing the PVL

toxin. The mecA gene can be acquired by both CA-MRSA and HA-MRSA. The pvl gene, on the other hand, is found normally in CA-MRSA but not in HA-MRSA.
Symptoms of MRSA. Methicillin-resistant staphylococcus aureus produces symptoms no different from any other type of Staphylococcus aureus bacteria. The skin will appear red and inflamed around wound sites. Symptoms in serious cases may include fever, lethargy, and headache. MRSA can cause urinary tract infections, pneumonia, toxic shock syndrome, and even death. Symptoms of MRSA infections are variable; however, pus production is often found in the infected area. Classic examples of pus-containing areas in patients are boils (pus in hair follicles), abscesses (collections of pus), carbuncles (large abscesses with pus draining), sty (pus in an eyelid gland), and impetigo (pus in blisters on the skin). Cellulitis (infection under the skin or fatty tissue) usually does not have pus but begins with small red bumps on the skin, sometimes with itching, and also may be due to MRSA.

Figure 2 : Shows Pus as one of the symptom of MRSA.

Risk Factor. Because hospital and community strains of MRSA generally occur in different settings, the risk factors for the two strains differ. Risk factors for HA-MRSA

Being hospitalized. MRSA remains a concern in hospitals, where it can attack those most vulnerable older adults and people with weakened immune systems. Having an invasive medical device. Medical tubing such as intravenous lines or urinary catheters can provide a pathway for MRSA to travel into your body. Residing in a long-term care facility. MRSA is prevalent in nursing homes. Carriers of MRSA have the ability to spread it, even if they're not sick themselves.

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

MRSA Infection Diagnosis The diagnosis of MRSA is established by culture of the bacteria from an infected area. Any area of the skin with pus, abscesses, or blisters should be cultured for MRSA. Patients with sepsis or pneumonia should have blood cultures drawn. Pus from surgical sites, bone marrow, joint fluid, or almost any body site that may be infected should be cultured for MRSA. Unfortunately, MRSA infections look like almost any staph infection initially, so identification of MRSA strains is important for the patient and doctor to consider. What makes an infection suspicious as being MRSA is when the symptoms worsen and seem unresponsive to antibiotic treatment.

The definitive laboratory studies to diagnose a MRSA are straightforward. S. aureus is isolated and identified from the patient by standard microbiological techniques (growth on Baird-Parker agar plates and a positive coagulase test). The coagulase test is a laboratory test based upon the ability of S. aureus to produce the enzyme coagulase that ultimately leads to the formation of a blood clot. After S. aureus bacteria are isolated, the bacteria are then cultured in the presence of methicillin (and usually other antibiotics). If S. aureus grows in the presence of methicillin, the bacteria are termed MRSA. The Kirby-Bauer method (shown below) shows clear areas where various antibiotics kill bacteria; MRSA bacteria show little or no clear areas to most antibiotics tested

MRSA Infection Treatment Antibiotic therapy is still the mainstay of medical care for MRSA, but antibiotic therapy is complicated by MRSA's antibiotic resistance. Consequently, laboratory determination of MRSA antibiotic resistance and susceptibility is important in establishing effective antibiotic treatment. Definitive antibiotic therapy depends on using those antibiotics shown in microbiological tests (using Kirby-Bauer antibiotic discs on agar plates [see above diagnosis section]) to effectively reduce and stop MRSA growth. Once the antibiotic sensitivities of the patient sample are determined, the patient can be treated appropriately. Unfortunately, these tests take time (usually several days) before results are available. If a patient has been diagnosed with a MRSA infection, as with all antibiotic therapies, it is important for them to take all antibiotics as directed; do not stop the antibiotic even if the symptoms seem to resolve before the prescribed dose is finished. Early stoppage of antibiotics can allow MRSA to survive and develop further antibiotic resistance. If initial medical care (especially antibiotic therapy) does not help to reduce or eliminate the symptoms, do not wait until the symptoms get worse; go back to a health care provider for further care. The majority of serious MRSA infections are treated with two or more intravenous antibiotics that, in combination, often still are effective against MRSA (for example, vancomycin, linezolid [Zyvox], rifampin [Rifadin], sulfamethoxazole-trimethoprim [Bactrim, Bactrim DS, Septra, Septra DS, SMZ-TMP DS, Sulfatrim Pediatric], and others). Minor skin infections, however, may respond well to mupirocin (Bactroban). The earlier the appropriate diagnosis and therapy is instituted for MRSA, the better the prognosis. The CDC suggests that a number of different antibiotic regimens may work to help patients based on the type of infection, its severity, and the state of the patient (child, adult, pregnant, or compromised with health problems); the CDC recommends following guidelines published by the Infectious Diseases Society of America in 2011. Drainage of pus is the main surgical treatment of MRSA infections. Items that can serve as sources of infection (tampons, intravenous lines) should be removed. Other foreign bodies present that are likely sources of infection (for example, artificial grafts, artificial heart valves, or pacemakers) may need to be removed if appropriate antibiotic therapy is unsuccessful. Other areas that can harbor MRSA and may need surgical interventions are joint infections, postoperative abscesses, and infection of the bone (osteomyelitis). This is not an all-inclusive list; any site that continues to harbor and seed MRSA into the patient and is not adequately treated by antibiotic therapy should be considered for surgical intervention. Drainage of pus needs to be followed by appropriate antibiotic therapy as discussed above.

MRSA Infection Prevention The best way to avoid MRSA infection is not making direct contact with skin, clothing, or any items that come in contact with either MRSA patients or MRSA. This is often not possible because MRSA-infected individuals or MRSA carriers are not immediately identifiable. A first step is excellent hygiene practices (for example, hand washing with soap after personal contact or toilet use, washing clothes potentially in contact with MRSA patients or carriers, and using disposable items such as gloves when treating MRSA patients). Antiseptic solutions and wipes are available at most stores to both clean hands and surfaces that may contact MRSA. These are useful at home, in gyms, or almost any public place such as a public restroom. As long as the infected person has viable MRSA in or on the body, they are considered contagious.

Another prevention method is to treat and cover (for example, antiseptic cream and a Band-Aid) any skin breaks. Pregnant women need to consult with their doctors if they are infected or are carriers of MRSA. Although MRSA is not transmitted to infants by breastfeeding unless the nipple(s) are infected, there have been a few reports that infants can be infected by their MRSApositive mothers, but this seems to be an infrequent situation. Some pregnant MRSA carriers have been successfully treated with the antibiotic mupirocin cream (Bactroban). Caregivers to MRSA patients usually can avoid getting infected by good hygiene (hand washing, using towels, linens and clothing that may contact the patient only once and then washing). Disposable gloves should be used when changing dressings or when one is likely to contact body fluids, including saliva. General screening of people is only recommended for high-risk patients who are being admitted to the hospital according to 2010 CDC guidelines. This is usually done by the infection-control group in hospitals. Some hospitals have already instituted this practice: since MRSA infections have begun to decrease, investigators suggest this practice, along with good home care (after diagnosis and treatment), is responsible for the recent decreases in MRSA infections in the U.S.

MRSA and Pregnancy If a pregnant woman is a MRSA carrier, there is no research evidence that her pregnancy will be compromised. In general, MRSA screening is not done routinely during pregnancy. However, if a woman has been diagnosed previously with MRSA, and if she is having a planned Csection, has a high risk for complications, has a MRSA-positive household member, or has been hospitalized in the last three months, she may be screened for MRSA. Some clinicians will offer treatment to suppress the bacteria; other clinicians may not, depending on the mother's circumstances. Pregnant women who get MRSA infections are treated with antibiotics; if they pass MRSA to their infant, the baby can also be treated. Fortunately, serious MRSA infections in infants are rare. Pregnant women with MRSA infections should be treated by specialists, usually a team consisting of an ob-gyn and infectious-disease consultant, since careful choices in antibiotics and close follow-up yield the best outcomes for the mother and baby.

Figure 4 : Shows the image of a pregnant lady having MRSA

Figure 5 : Shows the microscopic image of MRSA

Discussion.
Staphylococcus aureus (S. aureus) is one of the most important bacterial opportunistic pathogens in humans. It easily adapts to the various environmental conditions. Very important is rapid development of resistance to different antimicrobial agents. Especially important is the resistance to beta-lactam antibiotics (so called methicillin-resistant S. aureus: MRSA). MRSA strains differ according to the setting they cause infections to healthcare-acquired strains, community-acquired strains and animal strains. Healthcare-acquired MRSA strains were responsible for the largest epidemic of healthcare-associated infections that ever occurred in the world; community-acquired MRSA strains are huge problem in USA, not so important in Europe. Animal MRSA strains are new addition to human pathogens, but they are not very frequent. In Croatia, MRSA strains are big problem in hospitals but with the tendency of decreasing in recent years; community- acquired MRSA strains are so far very rare, and infections caused by animal MRSA strains are still not described in humans, although they are present in pig farm. An especially important characteristic of the adaptability of S. aureus is the fact that it can obtain very quickly resistance to various antibiotics. Already about ten years after the discovery of penicillin, resistance appeared to penicillin, and today about 80-90% of strains of S. aureus produce beta-lactamase which destroys penicillin directly after the introduction of methicillin into clinical practice (1959-1960), the first methicillin resistant S. aureus (MRSA) was isolated. In 1961 in the United Kingdom, it was found in the blood of a patient with bacteraemia . MRSA strains differ according to their sensitivity to other anti-staphylococcal antibiotics, but they are most often resistant to most of them. Reduced sensitivity and so-called hetero-resistance to vancomycin, today one of the primary drugs used for treating MRSA infection, was described in 1997 , and since 2002 several cases of resistance to vancomycin have been described - but it has not spread further than the few cases described . However, an increase in minimal inhibitory concentrations of vancomycin is developing in MRSA strains, which is resulting in a reduction in the effectiveness of that drug too. The occurrence of MRSA strains has even been described to new drugs available in this country, that is, linezolid and daptomycin.MRSA strains have also developed resistance to all other antibiotics used to treat staphylococcal infection (macrolides, lincosamides, streptogramin B, quinolones, cotrimoxazol, rifampicin, fusidic acid).Resistance to methicillin is mediated by the production of PBP 2a, coded by the gene mecA, located within the staphylococcal chromosomal cassette SCCmec. PBP2a, in contrast to PBP in sensitive strains, has a very weak affinity for beta-lactam antibiotics, and MRSA strain is resistant to all beta-lactam antibiotics.

References.
Books.

1. Wertheim HF, Melles DC, Vos MC (2005). The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis. 751762. 2. Kluytmans J, van Belkum A, Verbrugh H (1997) Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Pg 100-120 3. Williams REO, Jevons MP, Shooter RA, et al.(1959) Nasal staphylococci and sepsis in hospital patients. Pg 65862. Internet Resources.
1. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474459/ 2. http://www2.uwrf.edu/caseit/mrsa.html

3. http://www.mayoclinic.com/health/mrsa/DS00735