Mrsa | MRSA And Its Treatment

1. Introduction

1.1 Staphylococcus aureus

Staphylococcus aureus is a facultative anaerobic, Gram-positive coccus and itappears as grape-like clusters when viewed through a microscope and has large, round, golden-yellow colonies. The carotenoid pigment staphyloxanthin is responsible for Staphylococcus aureus’ characteristic golden colour, which may be seen in colonies of the organism. This pigment acts as a virulence factor with an antioxidant action that helps the microbe evade death by reactive oxygen species used by the host immune system. Staph organisms which lack the pigment are more easily killed by host defenses.

Staphylococcus aureus is catalase-positive and this property is useful in distinguishing staphylococci from enterococci and streptococci. It is primarily coagulase-positive, while most other Staphylococcus species are coagulase-negative.

Depending on the strain, S. aureus is capable of secreting several toxins such as Super antigens, Exfoliative toxins, and other toxins like as alpha-toxin, beta-toxin, delta-toxin, and several bicomponent toxins. Many of these toxins are associated with specific diseases.

It is frequently part of the skin flora found in the nose and on skin. Staphylococcus aureus commonly carried on the skin or in the nose of healthy people. Approximately 25% to 30% of the human populations are long-term carriers of Staphylococcus aureus in the nose. It can also be carried in the armpit, groin, or genital area. Staph bacteria are one of the most common causes of skin infections in the United States. Most of these skin infections are minor such as pimples and boils and can be treated without antibiotics. However, it can also cause serious infections such as pneumonia, bloodstream infections, and joint infections

Staphylococcus aureus is an important nosocomial and community-acquired pathogen. It is the most common cause of hospital acquired infection, causing clinical disease. In the past, these staph infections typically have been easy to treat with an inexpensive, short course, usually well-tolerated antibiotics. Now over half of the staph causing skin infections are resistant to commonly used antibiotics and the infections often return in spite of apparently successful initial treatment.

1.2 Methicillin resistant Staphylococcus aureus

MRSA strain is a strain of Staphylococcus aureus bacterium,resistant to antibiotic methicillin and other commonly used anyibiotics such as penicillin.

MRSA has undergone rapid evolutionary changes and epidemiologic expansion to become a major cause of nosocomial and community-acquired infections worldwide since its discovery 4 decades ago.

Meticillin or methicillin is a narrow spectrum beta-lactam antibiotic of the penicillin class developed in 1959 and was previously used to treat infections caused by beta-lactamase producing Staphylococcus aureus ; a semi-synthetic penicillin-related antibiotic, also known as Staphcillin, was once effective against staphylococci resistant to penicillin because they produce the enzyme penicillinase. European hospitals observed methicillin-resistant strains of S. aureus just two years later, and by the 1980s MRSA had become widespread in hospitals throughout the world, including Siberia and India.

The first few cases of MRSA from India were reported in 1996.

Originally MRSA was confined to hospitals and long-term care facilities; taking antibiotics was a risk factor for infection with MRSA. Infected and colonized residents may serve as potential sources for the spread of MRSA in long-term care facilities. Elderly residents are at increased risk for colonization with MRSA, in addition to having the potential to carry MRSA for long periods of time.

Methicillin has been superceded by Vancomycin. Distribution of Staphylococcus aureus is worldwide: As many as 11%-40% of the population is estimated to be colonized. Bacterial strains of Staphylococcus aureus can produce proteolytic enzymes, exfoliative, and exotoxin TSST-1. Adding antibiotic resistance to this long list of pathogenic mechanisms makes MRSA a formidable superbug. Because MRSA is so antibiotic resistant, it is termed a “super bug” by some investigators.

2. Categories of MRSA

MRSA has been classified into two categories based on the circumstances of acquiring diseases.

2.1 Hospital-Associated MRSA (HA-MRSA)

HA-MRSA occurs most frequently among patients who undergo invasive medical procedures or who have weakened immune systems and are being treated in hospitals and healthcare facilities such as nursing homes and dialysis centers. MRSA in healthcare settings commonly causes serious and potentially life threatening infections, such as bloodstream infections, surgical site infections or pneumonia.
The most common sources of transmission in the case of HA- MRSA, are patients who already have an MRSA infection or who carry the bacteria on their bodies but do not have symptoms (colonized).

2.2 Community-Associated MRSA (CA-MRSA)

MRSA infections that occur in otherwise healthy people who have not been recently hospitalized nor had a medical procedure such as dialysis, surgery, catheters are categorized as community-associated (CA-MRSA) infections. These are usually skin infections, such as abscesses, boils, and other pus-filled lesions.

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, spread more rapidly and cause more severe illnessthan traditional HA-MRSA infections, and can affect vital organs leading to widespread infection, sepsis, toxic shock syndrome and pneumonia. The origin of CA-MRSA infection can be elusive.

CA-MRSA skin infections have been identified among certain populations that share close quarters or experience more skin-to-skin contact, in situations where there is close skin-to-skin contact; when personal items such as towels, razors, and sporting equipment is shared; when personal hygiene is compromised; and when healthcare is limited. CA-MRSA is genetically distinct from the strains prevalent in hospitals, and can cause infections in young people with no connection to healthcare environments. Examples are team athletes, military recruits, and prisoners.

3. History

Brief timeline:

1940 Penicillin introduced

1942 Penicillin-resistant Staphylococcus aureus appears

1959 Methicillin introduced; most Staphylococcus aureus strains in both hospital and community settings are peniciillin resistant

1961 Methicillin-resistant Staphylococcus aureus (MRSA) appears

1963 First hospital outbreak of methicillin-resistant Staphylococcus aureus

1996 Vancomycin-resistant Staphylococcus aureus (VRSA) reported in Japan

The Staphylococcus aureus bacterium was discovered in the 1880s. In the 1940s, medical treatment for Staphylococcus aureus infections became routine and successful with the discovery and introduction of antibiotic medication, such as penicillin. Since then the use of antibiotic i.e. both 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 all through the 1950s, Staphylococcus aureus developed resistance to penicillin.

Methicillin, a form of penicillin, was introduced to counter the increasing crisis of penicillin-resistant Staphylococcus aureus . Methicillin was one of most common types of antibiotics used to treat Staphylococcus aureus infections; but, in 1961, scientists identified the first strains of Staphylococcus aureus bacteria that resisted methicillin. This was the supposed birth of MRSA.

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

In 2002, physicians in the United States recognized the first Staphylococcus aureus strains resistant to the antibiotic, vancomycin, which had been one of a handful of alternative antibiotics against Staphylococcus aureus . Though it is feared that this could rapidly become a major concern in antibiotic resistance, thus far, vancomycin-resistant strains are still rare at this time.

4. Causes

A genetic element that can be transferred from one bacterium to another causes Staphylococcus aureus to develop resistance to antibiotics. At least five types of genetic material SCCmec genes I-V are known. HA-MRSA usually have genes I-III while CA-MRSA have genes IV-V. HA-MRSA is resistant to more antibiotics than CA-MRSA.

MRSA can be transmitted by direct contact through 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 and can transmit MRSA to others.

Statistics show that CA-MRSA is the predominant MRSA type found in the population. Leading causes of antibiotic resistance includes unnecessary antibiotic use in humans. MRSA super bug is the result of decades of excessive and unnecessary antibiotic use. For years, antibiotics have been prescribed for colds, flu and other viral infections that don’t respond to these drugs, as well as for simple bacterial infections that normally clear on their own.

4.1 Common risk factors for acquiring MRSA

1. Hospitalization or confinement in a place where MRSA is endemic

2. Prolonged or multiple hospital stay

3. Age over 65 years

4. Invasive devices e.g., catheters, surgical drains, gastric endotracheal tubes

5. Treatment with multiple broad-spectrum antibiotics

6. Any conditions that suppress immune system function

7. Open wound or breaks in the skin e.g., scratches, abrasions, or punctures

8. Hospitalized patients usually have sites that are easily contaminated with MRSA

9. Unsanitary or crowded living conditions like dormitories or military barracks

10. Sharing towels or other personal items

11. Playing contact sport

12. Inpatient in a neonatal or surgical ICU

5. Symptoms

Staphylococcus aureus can cause a range of illnesses from minor skin infections, such as pimples, impetigo, boils or furuncles, cellulitis folliculitis, carbuncles, scalded skin syndrome, and abscesses, to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome (TSS), chest pain, bacteremia, and sepsis. Its incidence is from skin, soft tissue, respiratory, bone, joint, endovascular to wound infections. It is one of the five most common causes of nosocomial infections, often causing post surgical wound infections.

The symptoms of MRSA depend on the place of infection. Often, it causes mild infections on the skin, causing pimples or boils. But it can also cause more serious skin infections or infect surgical wounds, the bloodstream, the lungs, or the urinary tract.

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, abscesses, carbuncles, sty, and impetigo. Cellulitis usually does not have pus but begins with small red bumps on skin and also may be due to MRSA. These symptoms are most often found in CA-MRSA but can also be found in HA-MRSA. When antibiotic therapy fails, CA- and HA-MRSA should be considered as a potential cause of infection.

5.1 Symptoms of HA-MRSA

HA-MRSA infections are usually suspected when the hospitalized patient develops signs of sepsis like fever, chills, low blood pressure, weakness, and mental deterioration, even if the patient is being treated with an antibiotic.

5.2 Symptoms of CA-MRSA

CA-MRSA patients that develop sepsis or pneumonia (lung infection) need immediate hospitalization. However, hospitalized patients do not need to have a primary site of MRSA infection, only a site where MRSA can invade (invasive or serious MRSA) and proliferate e.g., any surgical site, IV site, or site of an implanted device. Consequently, symptoms of pus production or signs of sepsis in any hospitalized patient, especially those with immune compromise for example, HIV, cancer, or the elderly could be due to MRSA.

MRSA skin infections can look precisely like ordinary staph infections of the skin: a small red bump, pimple, or boil. The area may be red, painful, swollen, or warm to the touch. Pus or other fluids may drain from the sore. Most MRSA skin infections are mild, but they can change, becoming deeper and more serious.

Bug bites, rashes, and other skin conditions can be confused with MRSA because the symptoms may be similar: red, swollen, warm, or tender.

When a skin infection spreads or does not improve after 2-3 days on usual antibiotics, it may be MRSA.

Most MRSA infections are skin infections that produce the following signs and symptoms:

6. Diagnosis

MRSA infection can be diagnosed by positive culture together with signs/symptoms of infection. In positive culture case, MRSA is usually cultured from blood, wounds, respiratory secretions, urine, or surgical specimens. Common sites of infection and colonization include wounds, tracheostomy sites, respiratory tract of in-tubated patients, and IV catheter sites.

Colonization can be detected by culture of the organism from an asymptomatic patient. In this case, MRSA is usually cultured from the skin, nares, or rectum. After Staphylococcus aureus is identified, antibiotic susceptibility testing should be performed.

Certain patient populations, such as hemodialysis patients, intravenous drug users, those with dermatological diseases such as eczema, and patients with insulin-dependent diabetes mellitus, have increased rates of staphylococcal carriage.

The diagnosis of MRSA is established by culture of the bacteria obtained 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.

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

The definitive laboratory studies to diagnose that a person is infected with MRSA are straightforward. Staphylococcus 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 Staphylococcus aureus to produce the enzyme coagulase that ultimately leads to the formation of a blood clot. After Staphylococcus aureus bacteria are isolated, the bacteria are then cultured in the presence of methicillin (and usually other antibiotics). If Staphylococcus aureus grows in the presence of methicillin, the bacteria are termed MRSA.

Carriers of MRSA are detected by swabbing the skin, nasal passages, or throat of asymptomatic people and performing the culture techniques described above.

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 bacterial growth (a culture). It takes about 48 hours for the bacteria to grow. 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.

7. Treatment

MRSA is of special concern in regards to treatment because it is usually multi-drug resistant.

Hence pointless use of antibiotics should be discouraged . This reduces the survival advantage of MRSA and other resistant bacteria. Basic infection-control measures are critical to success. Careful evaluation of culture and sensitivity report should be taken into account.Infection is often confused with colonization and can lead to unnecessary utilization of antimicrobial agents. Potential anatomical sites of colonization include the anterior nares, axillae, upper extremities, urinary tract and perineum

The treatment of choice for Staphylococcus aureus infection was penicillin; but, in most countries, penicillin-resistance is extremely common and first-line therapy is most commonly a penicillinase-resistant -lactam antibiotic for example, oxacillin or flucloxacillin

Healthcare providers can treat many S. aureus skin infections by draining the abscess or boil and may not need to use antibiotics. Drainage of pus is the main surgical treatment of MRSA infections. Items that can serve as sources of infection such as tampons; intravenous lines etc should be removed. Other foreign bodies present that are probable 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 osteomyelitis. 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. The drainage of pus should be followed by appropriate antibiotic therapy.

Bactrim and Vancomycin are now often the first drugs used for treating most MRSA infections caused by multi-drug resistant strains. Vancomycin has been effective in treating invasive MRSA, but must be administered intravenously.

There is substantial indication that active screening of high-risk patients, when combined with contact precautions, appropriate hand hygiene and education of personnel, can reduce transmission of MRSA, even in facilities where it is highly endemic.

1. Many minor MRSA infections can be successfully treated with trimethoprim sulfamethoxazole, if susceptibility is established by testing. Uses of topical agents such as mupirocin, and antibacterial soaps have had some worth in the absence of foci of active infection. Mupirocin is a bacteriostatic antibiotic used exclusively as a topical agent and its intranasal application is effective in reducing surgical site infections and the likelihood of bronchopulmonary infection. It exerts its antimicrobial effect by specifically and irreversibly binding to bacterial isoleucyl tRNA synthetase, thus preventing protein synthesis. It has been used widely for the clearance of nasal MRSA carriage during outbreaks.

2. Clindamycin, co-trimoxazole, fluoroquinolones or minocycline may be useful when patients do not have life-threatening infections caused by strains susceptible to these agents.

3. For serious infections caused by strains that are susceptible to rifampin, combination therapy with vancomycin or fluoroquinolone may contribute to improved outcomes. Rifampin should not be used alone to treat MRSA infections due to the rapid development of resistance. The infecting strain always should be tested for susceptibility prior to initiating any of the therapies .

The two newest antimicrobials, quinupristin-dalfopristin (Synercid) and linezolid (Zyvox) also are effective for MRSA infections, though routine use is usually discouraged to prevent further resistance to these agents. Other investigational agents are in research stages but not yet approved for use.

The majority of serious MRSA infections are treated with two or more intravenous antibiotics that, in combination, are effective against MRSA for example, vancomycin, linezolid, rifampin, sulfamethoxazole-trimethoprim, and others. Combination therapy with gentamicin may be used to treat serious infections like endocarditis, but its use is controversial because of the high risk of damage to the kidneys.

The duration of treatment depends on the site of infection and on severity. Treatment with fluoroquinolones or cephalosporin antibiotics can however increase the risk of HA-MRSA.
That is why in addition to most beta-lactams, MRSA is also becoming resistant to erythromycin, aminoglycosides, fluoroquinolones, co-trimoxazole and rifampin.

Of late, there have been reports of vancomycin failure due to either relative vancomycin resistance or MRSA infections in sites that have poor vancomycin penetration. Few drugs like linezolid, tigecycline, and daptomycin shows potential in treatment. While Daptomycin an acidic lipopeptide with a mode of action requiring calcium has established significantly better bactericidal activity than vancomycin against S. aureus and enterococci and has activity against a small number of glycopeptide-intermediate S. aureus (GISA) strains and vancomycin resistant enterococcus

Antibiotic therapy is still the core of medical care for MRSA, but it is complicated by MRSA’s antibiotic resistance. Therefore, 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 to effectively reduce and stop MRSA growth. Once the antibiotic sensitivities of the patient sample are determined, the patient can be treated appropriately. Regrettably, these tests take time, usually several days before results are available. The earlier the appropriate diagnosis and therapy is done for MRSA, the better the prognosis.

Unfortunately, patients can still die from MRSA infection, even with appropriate antibiotic therapy, if the infection overwhelms the patient’s defense mechanisms i.e. immune system.

8. Protection from MRSA

Spread of MRSA is through human-to-human contact, the infection can also spread through pets. One can get MRSA by touching a person who carries the bacteria or by touching something that an infected person has touched.
Following things have been associated with the spread of MRSA:

1. Close skin-to-skin contact

2. Openings in the skin, like cuts or abrasions

3. Contaminated items and surfaces

4. Crowded living conditions like in hospitals or prisons

5. Poor hygiene

In health care centers, people who carry MRSA are sometimes isolated from other patients to prevent the bacteria from spreading. Carriers of MRSA have the ability to spread it, even if they’re not sick themselves. Because hospital and community strains of MRSA generally occur in different settings, the risk factors for the two strains differ. MRSA remains a concern in hospitals, where it can attack those most vulnerable older adults and people with weakened immune systems, burns, surgical wounds or serious underlying health problems. People who are on dialysis, are catheterized, or have feeding tubes or other invasive devices are at higher risk.

Staphylococcus aureus is an incredibly hardy bacterium; it can survive on polyester for just under three months, polyester being the main material used in hospital privacy curtains is a major area of concern. The bacterium is transported on the hands of healthcare workers who may pick up the bacteria from a seemingly healthy patient carrying a “benign” or commensal strain of S. aureus and then pass it on to the next patient. Introduction of the bacterium into the bloodstream can lead to various complications including, endocarditis, meningitis, and sepsis.

8.1 Protection from hospital-acquired MRSA infections (HA-MRSA):

An important and until now an unrecognized means of community-associated MRSA colonization and transmission is during sexual contact. Some people habitually share razors or combs, since a person can unknowingly carry the bacteria that cause staph infection, using another person’s comb, brush, towel or razor can increase the risk of infection

8.2 Protection from Community -acquired MRSA infections (CA-MRSA):

1. Wash hands. Careful hand washing remains best defense against germs.

2. Keep personal items personal. Avoid sharing personal items such as towels, sheets, razors, clothing and athletic equipment. MRSA spreads on contaminated objects as well as through direct contact.

3. Keep wounds covered. Keep cuts and abrasions clean and covered with sterile, dry bandages until they heal. The pus from infected sores may contain MRSA, and keeping wounds covered will help keep the bacteria from spreading.

4. Shower after athletic games or practices. Shower immediately after each game or practice. Use soap and water. Don’t share towels.

5. Sit out athletic games or practices if you have a concerning infection. If a person has a wound that’s draining or appears infected ” for example is red, swollen, warm to the touch or tender ” consider sitting out athletic games or practices until the wound has healed.

6. Sanitize linens. If a person has a cut or sore, wash towels and bed linens in a washing machine set to the “hot” water setting with added bleach,

7. Get tested. If a person has a skin infection that requires treatment, then doctors may prescribe drugs that aren’t effective against antibiotic-resistant staph, which delays treatment and creates more resistant germs. Testing specifically for MRSA may get the specific antibiotic needed to effectively treat the infection.

8. Use antibiotics appropriately. When prescribed an antibiotic, one should take all of the doses, even if the infection is getting better. Don’t stop until the doctor advises so. One shouldn’t share antibiotics with others or save unfinished antibiotics for another time. Inappropriate use of antibiotics, including not taking all of the prescribed medicines and overuse, contributes to resistance.

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