MRSA infection

(Date of publication 23 April 2004)

There is no doubt that MRSA (methicillin-resistant Staphylococcus aureus) is one of the outstanding bacterial success stories of our time, and its tabloid nickname 'superbug' is well deserved. The UK Health Protection Agency recently reported that the number of deaths involving this bacterium increased more than 15-fold between 1993 and 2002, and the incidence of MRSA bacteraemia increased 24-fold over the same period. In March 2004, researchers at St George's Hospital in London reported an alarming 19-fold increase in MRSA infection rates in children between 1990 and 2001, and the same BBC News item cites evidence from the USA that up to 60% of childhood cases are acquired outside hospital, suggesting that MRSA is circulating in the community. If you want to learn about the emergence of this virulent pathogen, which even in the year 2000 was costing the health sector in England almost £1 billion each year, try this article in the Biomedical Scientist.

Staphlococcus aureus is a Gram-positive bacterium which is immobile, forms clusters and grows mainly by aerobic respiration. It is a commensal of the nasal mucous membranes and skin of healthy humans, and an extremely versatile pathogen, but infections are usually localised at the point of entry by the host's defences . (This page has some particularly good colour photomicrographs.)

The generally accepted criterion for identifying Staphlococcus aureus is its ability to clot plasma. It can cause infection by two mechanisms: tissue invasion and toxin production. The classical lesion resulting from tissue invasion is the abscess, consisting of a fibrin wall surrounded by inflamed tissues, and enclosing a central core of pus which contains organisms and leukocytes . If you want to look at a prime specimen on a patient's wrist, click here. Other sites of infection include the lungs, bones, joints and heart valves.

One common toxin-mediated condition is gastroenteritis, resulting from the absorption of staphylococcal enterotoxins formed in food before it was consumed. The organism is able to grow over a wide range of temperatures and can affect many different foodstuffs, including milk and cream, pastries, butter, ham, cheese, sausages, canned meat, salads, cooked meals and sandwich fillings. However, contamination is readily avoided by careful heat treatment. The dose required to induce staphylococcal food poisoning in humans is estimated to be around 0.1 µg, but may vary with patient sensitivity.

The most feared manifestation of toxin production is toxic shock syndrome, a rare, life-threatening bacterial intoxication which can progress rapidly in previously healthy individuals of any age, especially post-surgical patients. It was first identified some 25 years ago in women using highly absorbent tampons, but these have since been modified, so that it is now most frequently seen in children and the elderly. Symptoms include dangerously low blood pressure, decreased kidney function, bleeding problems, rash, liver impairment and difficulty in breathing. Some authorities calculate the mortality rate to be as high as 5%.

The treatment of Staphlococcus aureus infections was revolutionised in the 1940s by the introduction of penicillin, but most strains have now developed resistance to the drug - and related antibiotics - by developing the capacity to produce b-lactamases. These are enzymes which hydrolyse b-lactams, the active ingredients in these antibiotics which have their effect by inhibiting the synthesis of bacterial cell walls.

Some related antibiotics, such as methicillin and flucloxacillin, are not affected by b-lactamases, but MRSA strains have unfortunately developed resistance to these drugs as well. The mechanism involves the expression of a foreign penicillin-binding protein (PBP) that is unaffected by methicillin, and the ability to do this is believed to be conferred by a large chunk of foreign DNA in the chromosome - known as the mec element - that may have originated from Staphlococcus sciuri, although it is not known how. This paper from Science Progress deals exclusively with the mechanisms and modulation of methicillin resistance, but it is very comprehensive, running to some 16 pages.

MRSA infections occur most often in hospital patients, especially those with wounds, indwelling catheters or burns, and those who are immunocompromised. It has been reported that patients from the poorest socio-economic backgrounds could be up to seven times more likely to get postoperative infection with MRSA than people from more affluent social groups, and that the increased risk probably results from their higher number of hospital visits rather than community-based MRSA infection. This UK study of patients undergoing coronary artery bypass surgery found that patients who contracted post-operative MRSA infection had a six-fold higher death rate, unlike earlier research which concluded that MRSA infection in surgical patients does not increase mortality.

As with ordinary strains of Staphylococcus aureus, some patients harbour MRSA on the skin or in the nose without harm, and are said to be 'colonised' . These individuals may be treated with mupiricin to eliminate the MRSA and prevent bacterial spread. The unique mechanism of action of this agent - it blocks the activity of an enzyme called isoleucyl-tRNA synthetase - makes it unlikely that bacteria will be resistant to it as a result of exposure to other antibiotics.

MRSA infections tend to be resistant to antibiotics such as erythromycin and ciprofloxacin, but most remain susceptible to vancomycin and teicoplanin. Both these drugs must be administered by injection or infusion, so their use is generally restricted to hospitalised patients. More information about vancomycin, which is effective against Gram-positive bacteria and acts by inhibiting cell wall synthesis, can be found here (the red links don't work!). A more recent addition to the armoury is linezolid, the first of a completely new class of antibiotics, the oxazolidinones. It is not only safe and effective, but can be administered orally as well as intravenously - for an account of a recent large scale clinical trial, go to the unlikely source of the Los Angeles Regional Office of Public Affairs.

However, it must not be forgotten that an important element in fighting the spread of MRSA in hospitals is extremely low-tech. Simple hygiene measures such as scrupulous hand-washing, isolating patients with MRSA and the use of disposable gloves and gowns are relatively easy to institute - and the cost is minimal compared to the alternative!

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A Tour around MRSA Infection

A Tour around MRSA Infection