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Methicillin-resistant staphylococcus aureus (MRSA)

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Related Terms
  • Antibiotic pressure, antibiotic resistance, antibiotics, CA-MRSA, community-associated-MRSA, enterotoxin, HA-MRSA, hospital-acquired-MRSA, mecA, methicillin resistance, MRSA, mutation, SFP, SSSS, staphylococcal food poisoning, staphylococcal scalded-skin syndrome, Staphylococcusaureus, toxic shock syndrome, TSS.

Background
  • Staphylococcus aureus (S. aureus) is an extremely versatile bacterium that can cause infections ranging in severity from mild to severe in humans and animals. S. aureus is normally found on the skin or in the nasal passages of about one third of the population. Most individuals harboring S. aureus are not ill but are "colonized" with the bacteria. Individuals who are colonized with S. aureus may develop infection if the bacteria enter the body through a break in the skin or nasal passages. Individuals who are colonized have the ability to spread the organism, even if they are not ill. If the bacteria are transmitted to another individual, they may cause infection in that individual. The ability of bacteria to resist the effects of an antibiotic is called antibiotic resistance. During the past decade, antibiotic resistance has increased tremendously worldwide.
  • Methicillin is a type of penicillin that was developed in 1959 to treat infections from S. aureus and other bacteria that were resistant to earlier forms of penicillin. Since that time, however, S. aureus and other bacteria have developed resistance to methicillin. Methicillin-resistant Staphylococcus aureus (MRSA) is now a global health concern. MRSA is highly virulent and can cause a large number of serious illnesses that do not respond well to current medical treatment.
  • MRSA has adapted in ways that allow it to be resistant to a number of antibiotics, including penicillin, methicillin, and cephalosporins. This adaptation or evolution, has been accomplished by mutation of the genetic material contained in S. aureus. The mutated bacteria are less or no longer susceptible to damage from methicillin.
  • MRSA was first noted in 1961, about two years after methicillin was initially used to treat S. aureus and other infectious bacteria. The resistance to methicillin was caused by a penicillin-binding protein coded for by a mobile genetic element (MGE). An MGE is a type of genetic material that has the ability to move genetic material from one organism to another. The MRSA MGA gene is called the methicillin-resistant gene (mecA). This gene has continued to evolve and, thus, many MRSA strains are currently resistant to several different antibiotics.
  • MRSA infections commonly occur in hospitals and other healthcare facilities, such as nursing homes. MRSA acquired in a hospital is known as hospital-acquired-MRSA (HA-MRSA) and infections transmitted within a hospital are known as nosocomial infections. Patients in healthcare facilities often have had a recent bacterial infection and have received antibiotics. A number of these patients have become colonized with bacterial strains that are resistant to antibiotics. Hospital workers who care for these patients may also become colonized.
  • MRSA infections that occur in healthy people who have not undergone a medical procedure or hospitalization within the past year are known as community-associated-MRSA (CA-MRSA) infections. These infections are usually located on the skin and appear as abscesses, boils, and other pus-filled lesions. Currently 10% of all MRSA infections in the United States are CA-MRSA. Individuals with a weakened immune system are particularly susceptible to MRSA.
  • Not only has S. aureus developed resistance to methicillin, it has developed resistance to newer antibiotics. As new antibiotics are developed, it is likely that this highly-adaptable bacterium will develop resistance to them as well.
  • Research in the field of genomics may aid in the treatment of MRSA infection. As researchers gain further understanding of the MRSA genome, the outlook for patients with this disease may improve.

Signs and symptoms
  • Staphylococcal skin infections, including methicillin-resistant Staphylococcus aureus (MRSA), often remain on the skin. However, they sometimes penetrate into the body and can cause life-threatening infections in the bloodstream, lungs, heart valves, surgical incisions, bones, and joints.
  • MRSA infections on the skin usually start as small red bumps that look like pimples, boils, or spider bites. These infections can quickly become deep, painful abscesses.

Diagnosis
  • Diagnosis of methicillin-resistant Staphylococcus aureus (MRS) is made by obtaining a culture from an infected area. Any area of the skin that has blisters, pus, or abscesses should be swabbed for MRSA. Cultures can also be obtained from the nasal passages, mouth, bone marrow, joint fluid, or surgical sites to test for MRSA.
  • Cultures are grown in a standard laboratory technique and exposed to methicillin. If Staphylococcus aureus continues to grow in the presence of methicillin, the bacteria are considered MRSA.
  • Carriers of MRSA can be diagnosed by swabbing the skin, nasal passages, or throat of individuals with no symptoms of infection and performing the same laboratory techniques described above.

Complications
  • S. aureus can cause toxin-mediated diseases, such as toxic shock syndrome (TSS), staphylococcal food poisoning (SFP), and staphylococcal scalded-skin syndrome (SSSS). TSS is a rare but serious infection that was originally linked with tampon use. It also can occur after bacteria penetrate the skin after a cut or surgical procedure. Symptoms include the sudden onset of a high fever, diarrhea, headache, and muscle aches. Skin and internal organ damage occur because of toxins released by the bacteria.
  • SFP is a common type of food poisoning. Many types of foods can become contaminated with bacteria that produce toxins. Contamination usually occurs in foods that are not kept hot or cold enough. Symptoms appear suddenly and may include nausea, vomiting, and diarrhea. Most people recover completely in two to three days.
  • SSSS appears as a sloughing of an area of skin that turns into a reddish, infected area. Similar to TSS and SFP, the skin damage is caused by a toxin released by the bacteria. The infection occurs mainly in children and newborns. It is rare in adults. Usually, the infected area heals in one to two weeks.

Treatment
  • Staphylococcal skin infections, including MRSA, usually first appear as small red bumps, which can quickly develop into abscesses that require surgical drainage.
  • Antibiotic resistance appears to occur through spontaneous genetic mutations in the bacteria. These mutations reduce the sensitivity of a bacterium to a given antibiotic or class of antibiotics. A single mutation may impart resistance to an antibiotic, but multiple mutations appear to be required for resistance to other drugs.
  • Antibiotic resistance ranges from none (complete sensitivity) to high. In the face of life-threatening infections, a combination of antibiotics is often given to reduce the chance of an infection worsening because of antibiotic resistance.
  • Following the emergence of MRSA, the antibiotic vancomycin became the drug of choice for treating MRSA infections. However, there are now strains of MRSA that have become resistant to vancomycin as well. Other antibiotics used to treat MRSA include teicoplanin, linezolid, and daptomycin.

Integrative therapies
  • Note: There is currently a lack of scientific evidence for the use of integrative therapies in the treatment or prevention of methicillin-resistant Staphylococcus aureus (MRSA). The therapies listed below have been studied for bacterial infections in general, should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies.
  • Strong scientific evidence:
  • Probiotics: Probiotics are beneficial bacteria (sometimes referred to as "friendly germs") that help to maintain the health of the intestinal tract and aid in digestion. An increasing number of studies support the use of probiotics as a supplement to antibiotic therapy. Probiotic supplementation during a course of antibiotics may reduce the adverse effects of antibiotics in the intestinal environment. This includes reducing growth of Clostridium difficile bacteria, which can lead to colitis, a common complication of antibiotics, especially in the elderly. Some probiotics may also help prevent the development of antibiotic resistance. In acutely ill children, synbiotics have been linked to greater weight gain and fewer bacterial illnesses after antibiotics are ended. The evidence consistently supports supplementation of antibiotics. Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.
  • Good scientific evidence:
  • Probiotics: Antibiotics are the main treatment to eradicate Helicobacter pylori, the cause of most stomach ulcers. Side effects commonly include bloating, diarrhea, and taste disturbances. Probiotics have been shown to reduce these side effects and generally help people tolerate the treatment. They may also reduce levels of H. pylori in children and adults. Yogurt containing probiotics suppresses H. pylori infection and may lead to more complete eradication during antibiotic treatment. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.
  • Unclear or conflicting scientific evidence:
  • Blessed thistle: Blessed thistle leaves, stems, and flowers have traditionally been used in "bitter" tonic drinks and in other preparations taken by mouth to enhance appetite and digestion. Laboratory studies report that blessed thistle (and chemicals in blessed thistle such as cnicin and polyacetylene) has activity against several types of bacteria and a lack of effect on other types. Reliable human study is currently lacking. Further evidence is necessary in this area before a firm conclusion can be drawn. Avoid if allergic to blessed thistle, mugwort, bitter weed, blanket flower, chrysanthemum, coltsfoot, daisy, dandelion, dwarf sunflower, goldenrod, marigold, prairie sage, ragweed, Echinacea or any plants of the Asteraceae or Compositae families. Use cautiously with peptic ulcer disease. Avoid with a history of bleeding diseases or gastroesophageal reflux disease (GERD), or if taking drugs for blood thinning, stroke, stomach diseases, or to control stomach acid. Avoid if pregnant or breastfeeding. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures.
  • Cranberry: Cranberry has been investigated for numerous medicinal uses, and promising areas of investigation include prevention of H. pylori infection and dental plaque. Study results of cranberry as an antibacterial in other conditions show conflicting results. Further study is needed before a conclusion can be drawn. Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium genus. Sweetened cranberry juice can affect blood sugar levels. Use cautiously with history of kidney stones. Avoid more than the amount usually found in foods if pregnant or breastfeeding.
  • Lavender: Lavender is native to the Mediterranean, the Arabian Peninsula, Russia, and Africa. It has been used cosmetically and medicinally throughout history. In modern times, lavender is cultivated around the world and the fragrant oils of its flowers are used in aromatherapy, baked goods, candles, cosmetics, detergents, jellies, massage oils, perfumes, powders, shampoo, soaps, and tea. Early laboratory studies suggest that lavender oils may have antibiotic activity. However, this has not been well tested in animal or human studies. Avoid if allergic or hypersensitive to lavender. Avoid with history of seizures, bleeding disorders, eating disorders (anorexia, bulimia), or anemia (low levels of iron). Avoid if pregnant or breastfeeding.
  • Prayer: Prayer can be defined as a "reverent petition," the act of asking for something while aiming to connect with God or another object of worship. Prayer on behalf of the ill or dying has played a prominent role throughout history and across cultures. Prayer may help reduce the length of hospital stay as well as the duration of fever in patients with infections. However, early study is controversial and additional study is needed before a conclusion can be drawn. Prayer is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Sometimes religious beliefs come into conflict with standard medical approaches, and require an open dialog between patients and caregivers. In limited available human study, patients certain that they were receiving intercessory prayer had a higher incidence of complications following cardiac bypass surgery than those who did not know they were being prayed for.
  • Probiotics: As a bacterial reservoir, the nose may harbor many varieties of potentially disease-causing bacteria. There is limited evidence that probiotic supplementation may reduce the presence of harmful bacteria in the upper respiratory tract. More studies are needed to establish this relationship and its implications for health. Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant.
  • Propolis: Early study suggests that propolis may help treat various types of infections. Initial human research reports possible benefits against bacteria in the mouth, genital herpes, urine bacteria, intestinal giardia infections, or H. pylori. Additional research is needed before a recommendation can be made.
  • Seaweed, kelp, bladderwrack: Fucus vesiculosus is a brown seaweed that grows on the northern coasts of the Atlantic and Pacific oceans, and the North and Baltic seas. Its name is sometimes used for Ascophyllum nodosum, which is another brown seaweed that grows alongside Fucus vesiculosus. These species are often included in kelp preparations along with other types of seaweed. Laboratory study suggests antifungal and antibacterial activity of bladderwrack. Reliable human studies to support use as an antibacterial or antifungal agent are currently lacking. Avoid if allergic or hypersensitive to Fucus vesiculosus and iodine. Avoid with history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke, or diabetes. Avoid if pregnant or breastfeeding.
  • Selenium: Selenium is a trace mineral found in soil, water, and some foods. It is an essential element in several metabolic pathways. Preliminary research reports that selenium can be beneficial in the prevention of several types of infection, including recurrence of erysipelas (bacterial skin infection associated with lymphedema), sepsis, or Mycoplasma pneumonia. Selenium may help prevent infection by stimulating immune function. Further research is needed to confirm these results before a clear recommendation can be made. Avoid if allergic or sensitive to products containing selenium. Avoid with history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.
  • Sorrel: Historically, sorrel has been used as a salad green, spring tonic, diarrhea remedy, weak diuretic, and soothing agent for irritated nasal passages. Sorrel has been used with other herbs to treat bronchitis and sinus conditions in Germany since the 1930s. There is currently insufficient evidence to support the use of sorrel as an antibacterial. More research of sorrel alone is needed. Avoid with a known allergy to sorrel. Avoid large doses of sorrel because there have been reports of toxicity and death, possibly due to the oxalate found in sorrel. Many tinctures contain high levels of alcohol and should be avoided when driving or operating heavy machinery. High alcohol sorrel formulations may also cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding.
  • Fair negative scientific evidence:
  • Macrobiotic diet: A macrobiotic diet has been advocated to preserve intestinal health. However, it apparently does not reduce incidence of drug-resistant bacteria in the intestinal flora, nor infections caused by resistant strains in the gastrointestinal tract, compared to a diet with animal products.
  • Probiotics: Bacterial translocation (passage of bacteria from the gut to other areas of the body where they can cause disease) is of special concern in surgery. Limited evidence suggests that supplementation with probiotics may not reduce this problem.

Prevention
  • To effectively reduce the incidence of antibiotic resistance, it is necessary to reduce the antibiotic pressure in the bacterial environment, such as the intestinal tract, water supply, and animal reservoirs. Reducing the inappropriate use of antibiotics will reduce antibiotic pressure in the intestinal tract. Improved sanitary treatment of a community's water supply will reduce the antibiotic pressure in this area. Reduction of antibiotic pressure in animal reservoirs is a complex topic and involves identifying and destroying infected animals as well as reducing human contact with animals that might be reservoirs.
  • In the hospital setting, basic infection control practices, such as hand washing and the use of gloves, are essential to the prevention and control of methicillin-resistant Staphylococcus aureus (MRSA) and other drug-resistant organisms. Hospitalized patients diagnosed with MRSA are placed in isolation to minimize the spread of the organism.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
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  4. Chuck EA, Frazee BW, Lambert L, et al. The benefit of empiric treatment for methicillin-resistant staphylococcus aureus. J Emerg Med. 2008 May 29.
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  7. Grayson ML, Jarvie LJ, Martin R, et al. Significant reductions in methicillin-resistant Staphylococcus aureus bacteraemia and clinical isolates associated with a multisite, hand hygiene culture-change program and subsequent successful statewide roll-out. Med J Aust. 2008 Jun 2;188(11):633-40.
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  15. Wong HR, Cvijanovich N, Wheeler DS, et al. Interleukin-8 as a stratification tool for interventional trials involving pediatric septic shock. Am J Respir Crit Care Med. 2008 May 29.

Causes
  • Methicillin-resistant Staphylococcus aureus (MRSA) has adapted in ways that allow it to be resistant to a number of antibiotics, including penicillin, methicillin, and cephalosporins. This adaptation or evolution, has been accomplished by mutation of the genetic material contained in S. aureus. The mutated bacteria are less or no longer susceptible to damage from methicillin.
  • MRSA was first noted in 1961, about two years after methicillin was initially used to treat S. aureus and other infectious bacteria. The resistance to methicillin was caused by a penicillin-binding protein coded for by a mobile genetic element (MGE). An MGE is a type of genetic material that has the ability to move genetic material from one organism to another. The MRSA MGA gene is called the methicillin-resistant gene (mecA). This gene has continued to evolve and, thus, many MRSA strains are currently resistant to several different antibiotics.
  • Overuse of antibiotics is a major contributor to bacterial resistance. Unnecessary or more frequent use of an antibiotic increases the chance of a resistant strain developing. Antibiotic overuse has been termed "antibiotic pressure," which increases the chance of a resistant strain developing. Bacteria sensitive to the antibiotic are destroyed while bacteria resistant to the antibiotic flourish. Using the antibiotic on a resistant strain of bacteria favors the growth of the very microorganism that treatment is intended to eliminate.
  • Antibiotic pressure may also occur indirectly through inappropriate use of antibiotics. Examples of inappropriate uses include administration to patients with a viral upper respiratory infection, which is not affected by antibiotics, and addition to animal feed to promote growth.
  • A number of studies have found that patients frequently do not complete a full course of prescribed antibiotic treatment. This can promote the development of antibiotic resistance in some bacteria because they remain in the body and allow resistance to develop. Conversely, an excessively long course of antibiotic treatment adds to the antibiotic pressure, thus favoring the development of resistant strains.
  • S. aureus toxin-mediated diseases, such as toxic shock syndrome (TSS), staphylococcal food poisoning (SFP), and staphylococcal scalded-skin syndrome (SSSS), are caused by toxins produced by the bacteria. Complete recovery is the rule for SFP and SSS, while TSS has a high mortality rate.

Risk factors
  • The two types of methicillin-resistant Staphylococcus aureus (MRSA) include community-associated MRSA and healthcare-associated MRSA.
  • Community-associated-MRSA (CA-MRSA) risk factors: Individuals with a weakened immune system, such as those who have HIV/AIDS or are undergoing chemotherapy for cancer treatment, are at increased risk of serious infection from CA-MRSA.
  • CA-MRSA is especially dangerous in children. The bacteria can enter the body through a cut or scrape and the organism can then spread throughout the body. Children and young adults are also more susceptible to a CA-MRSA-induced form of pneumonia, which is a serious illness.
  • Crowded or unsanitary living conditions increase the exposure risk to CA-MRSA. CA-MRSA outbreaks have occurred in military bases and prisons. Athletic teams have an increased risk of exposure to CA-MRSA. The organism readily spreads from cuts, scrapes, and skin-to-skin contact. It can also be contracted from shared towels, uniforms, razors, and sports equipment. Close contact with healthcare workers increases the exposure risk to CA-MRSA. Individuals with multiple sexual partners are at increased risk of acquiring CA-MRSA.
  • Healthcare-associated-MRSA (HA-MRSA) risk factors: Individuals who are currently or were recently hospitalized are at increased risk of HA-MRSA, especially if they are older or have a weakened immune system. In addition to acute care hospitals, MRSA is also common in long-term care facilities. Patients with serious illness, recent surgery, burns, and hospitalization lasting more than two weeks are also more susceptible to HA-MRSA. Recent antibiotic treatment with cephalosporin or fluoroquinolones (ciprofloxacin, levofloxacin, or ofloxacin) can increase the risk of HA-MRSA. Patients who are attached to invasive devices, such as catheters, feeding tubes, and dialysis equipment, have an increased risk of HA-MRSA. Furthermore, after hospital discharge, patients harboring MRSA can spread the infection to friends and relatives.

Types of the disease
  • Methicillin-resistant Staphylococcus aureus (MRSA) infections commonly occur in hospitals and other healthcare facilities, such as nursing homes. MRSA acquired in a hospital is known as hospital-acquired-MRSA (HA-MRSA) and infections transmitted within a hospital are known as nosocomial infections. Patients in healthcare facilities often have had a recent bacterial infection and have received antibiotics. A number of these patients have become colonized with bacterial strains that are resistant to antibiotics. Hospital workers who care for these patients may also become colonized.
  • MRSA infections that occur in healthy people who have not undergone a medical procedure or hospitalization within the past year are known as community-associated-MRSA (CA-MRSA) infections. These infections are usually located on the skin and appear as abscesses, boils, and other pus-filled lesions. Currently 10% of all MRSA infections in the United States are CA-MRSA.

Research
  • Ongoing research is being conducted by pharmaceutical companies to develop new antibiotics as well as new forms of existing antibiotics. Studies have been conducted on the use of an antibiotic regimen to decolonize individuals who harbor MRSA. One study reported an 87% success rate in decolonizing MRSA carriers.
  • Interleukin-8 (IL-8) is a protein secreted by immune system cells. The level of IL-8 is under investigation as a predictor of outcome in patients with toxic shock syndrome. Patients with a lower IL-8 level at the time of hospital admission or diagnosis tend to have a higher chance of survival.
  • Apelin is a ligand molecule secreted by many tissues in the body. Apelin acts as a mediator for the control of blood pressure and blood flow. Serum apelin rises in patients with sepsis, which is a generalized infection of the body, and with septic shock, which comprises low blood pressure and a weak and rapid heart rate secondary to an infection. Research on serum apelin levels may provide clues for the diagnosis and prognosis (medical outcome) of septic shock.
  • Mitochondria are tiny subunits within a cell that are responsible for energy production. These subunits, or organelles, take in nutrients, break them down, and then produce energy for the cell. Many researchers believe that mitochondria are particularly susceptible to sepsis and that a breakdown of mitochondrial function is a key factor in organ failure in septic shock. One focus of current research, then, is on the understanding of mitochondrial mechanisms when a patient develops sepsis.
  • Genomics research has uncovered a specific mutation (a point mutation) in the MRSA gene that provides the bacterium resistance to vancomycin, which is the principal drug used to treat MRSA infections. In the process, two other factors were discovered that produce resistance. Identifying the specific genetics involved in MRSA is the first step in developing an effective treatment for this disease.

Future research
  • Future research will focus on the development of new antibiotics and the investigation of the genetic mechanisms involved in antibiotic resistance. Thiazolyl peptides have the potential to become potent antibiotics effective against MRSA. Recently developed agents are not very effective because of poor solubility (ability to dissolve in solution) and pharmaceutical properties (activity against infection). However, researchers are developing new types of thiazolyl peptides that may be very effective against MRSA infections.
  • Computer techniques exist for comparing S. aureus genomes. These techniques allow rapid comparison of genomes with only subtle differences (i.e., one that is resistant to a specific antibiotic and one that is not). This will lead to further experiments and ultimately to the development of new antibiotics or other therapies that can combat MRSA infections.
  • A fermented culture of the bacterium Streptomycesfulvissimus was found to secrete an antibacterial protein that inhibits MRSA and other disease-causing bacteria. This protein has the potential to become a source for the development of new drugs effective against MRSA and other pathogenic bacteria.
  • Research is ongoing to identify substances found in the blood of patients with toxic shock syndrome, such as apelin and interleukin-8. This research should improve the diagnosis of toxic shock syndrome and help predict disease outcome.
  • Future mitochondrial research will provide a better understanding of organ failure associated with toxic shock syndrome. A better understanding of this process may lead to improved methods of treatment.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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