The problem of antibiotic resistance of the bacterium Methicillin-resistant Staphylococcus aureus (MRSA) and to what extent it can be suppressed MRSA is a common type of bacteria often carried on the skin, inside the nostrils and the throat and can cause mild infections of the skin, such as boils and impetigo. “If staph bacteria get into a break in the skin, they can cause life-threatening infections, such as blood poisoning or endocarditis (an infection of the inner lining of the heart)”(4) MRSA was first discovered in the UK in 1961, just after methicillin, an antibiotic which became available for the use against ‘staph’ (Staphylococcus aureus) infections.(8) However due to the overuse of antibiotics, a common problem at the time, staphylococcus eventually became resistant and immune to the antibiotic Methicillin causing another deadly bacteria to form called MRSA. Initially there was no real problem as it took many decades for it to have any significant effect. “For example, in the US and the United Kingdom the proportion of S. aureus strains causing bacteraemia that was methicillin resistant started to increase around 1990, and by the start of the 21st century about half of the strains causing bacteraemia were resistant.”(8) In this case strains are referred to as the same species of bacterium but with a different function, for example one of the strains could be pathogenic but the other one is not. Recently new reports show that apart from the original hospitalized associated MRSA, a new strain has formed and is now known as the community associated MRSA.
This form of strain is becoming more common than hospitalized associated MRSA. (8) This form of MRSA often causes more skin infections, including cellulitis. Cellulitis is a bacterial infection of the deeper layers of skin and the layer of fat and soft tissues underneath the skin. (4) The main symptom associated with this infection is the skin quickly turning red, painful, hot and swollen.(4) Those who are at a younger age and have life styles consisting of close enclosures (i.e. prisoners or day care centres) are particularly prone to this form of infection.(8) In the UK and Wales the number of death certificates mentioning Staphylococcus aureus fell by 33.6% from 961 in 2010 to 638 in 2011.(9) Similarly, deaths involving MRSA fell by 24.9% from 485 in 2010 to 364 in 2011. Despite these improvements, the number of deaths from MRSA in 2011 is still seven times higher than in 1993 when data were first published. Figures also highlighted that those who lived in deprived areas showed increased death rates involving S.auerus and MRSA between 2006-2010. (9) Essentially MRSA has developed into a huge problem for health services, thriving in hospitals and medical care facilities.(4) This, together with its increasing ability of acquiring resistance to all current antibiotic classes gives its reputation as a ‘super-bug’. It is also proving to be a huge economic burden for many governments, costing millions and even billions of pounds each year. “Two surveys on all hospitals in the US estimated the occurrence and effects of S aureus infections over time. Infections increased from 258 000 in 1998 to 480 000 in 2005. In 2003, the associated costs of staphylococcal disease were around £10.3bn, and nearly 60% of the infections were caused by MRSA.” (8) To this day the evolutionary origins of MRSA are still poorly understood; nevertheless scientists still have a growing understanding of bacteria which promise better solutions to be evolved from. MRSA’s resistance
Strains of bacteria can mutate and over time become resistant to a specific antibiotic. Alternatively, if you are treated with an antibiotic, it can destroy many of the harmless strains of bacteria that live in and on the body. This allows resistant bacteria to quickly multiply and take their place. (4) Hospital patients are at a much higher risk of picking up a staph infection than normal; this is mainly because, the environment within a hospital is not only perfect for bacteria in terms of transmission of infections but also because of the general health of patients who tend to be much weaker and more vulnerable. (3) Once a patient develops an infection, urgent treatment with antibiotics is vital. MRSA being so resistant to many antibiotics is likely to overcome a weak patient very quickly. Basic understanding of bacteria tells us that their life spans are short but their population sizes come in masses.
These characteristics significantly increase the rate of which they can evolve. There are 2 main types of bacterial genetic evolution, one aspect in particular which allows the evolution of antibiotic resistance: (1) Evolution with vertical transmission – “An individual experiences a genetic mutation and if that mutation increases the individual’s ability to survive and reproduce, it is favoured by natural selection.” (1) Over time these gene variations are passed on to offspring from parent allowing the desirable mutation to spread throughout the future population, strengthening their abilities as bacteria of becoming more resistance. Evolution with horizontal transfer – “So bacteria acquire genetic variation through random mutation, but, unlike humans or oak trees, they also regularly get new gene variants through the process of horizontal transfer – that is, they can pass DNA back and forth to one another directly. For example bacterial genes can be incorporated into small self-replicating circles of DNA called plasmids, which can be “injected” into other bacteria.” (1)
The solution
Although MRSA is resistant to most antibiotics, some antibiotics still work. Bactrim and vancomycin are often the first drugs used to treat a patient. However there are other options such as clindamycin, minocycline, Tygacil, Cubicin, Zyvox, and Synercid. (10)
As shown by this table community associated MRSA is much more lethal than hospital associated MRSA. Of recent times CA-MRSA has become more of a problem to society being the most frequent cause of skin and soft tissue infections and replacing other MRSA strains in hospitals on a large scale. (15)The first choice solution currently for MRSA therapy is the use of the antibiotic mentioned above – vancomycin. (16) However community acquired forms of MRSA are not always treated with antibiotics. Sometimes simply draining any abscesses and keeping them clean is enough to resolve a MRSA infection. Vancomycin works by binding to a ‘D-alanyl-D-alanine’ cell wall messenger required for peptidoglycan cross-linking which is used for inhibiting bacterial cell wall synthesis and preventing the strains from growing. (19)
Vancomycin (VCM)
VCM with Beta-lactam
Antibiotic
improvement rate
in effectiveness of
MRSA infection cases
71.4%
77.8%
The rate of bacterial
eradication in cases
of single infection
against MRSA
71.4% 68.2%
The rate of bacterial eradication in polymicrobial infections including MRSA Only few cases were conducted using VCN alone therefore data was not representable 63.2%
We can tell from this data that VCM certainly works to an extent against MRSA. VCM alone shows a fairly high rate of success when dealing with MRSA infections and in some cases proves to be more useful when in tangent with a beta-lactam antibiotic. Although VCM is not 100% effective, 71.4% is still a significant amount and can be vital in supressing the MRSA strains enough to prevent them from reproducing in numbers that will cause infections. So as a result it is very difficult to determine the correct drug to use against MRSA in terms of providing a single one for all forms of MRSA strains. Countless studies have been done to provide data that prove certain antibiotics are most effective against certain types of infections. And it is still important to continue developing these drugs and provide an important mainstay against MRSA. This will only come as a result of continued variations of antibiotics to tackle the many forms of infections that can be acquired by this ever resistant super-bug. But for now determining the best treatment for antibiotic-resistant bacterium is always a delicate balance.
The right antibiotic should effectively cure the condition, run least risk of dangerous side effects and have the lowest tendency to cause bacteria to further evolve and become harder to treat in the future. Finding a medication that is the best choice proves very difficult and it is up to specialist to provide this information to us whilst they continue further research into this matter until a better solution is found. However as an addition to providing effective antibiotics, it’s important to maintain an environment which bacteria struggle to survive in. Or even to identify the problem before it can escalate, i.e. the use of screening. As I mentioned previously hospitals and medical centres in general consist of an environment which bacteria thrive on, MRSA being no different. The conditions within a hospital make it very suitable for bacteria to transmit and spread very sufficiently. This is why “All hospitals have infection control procedures and policies and staff take every precaution to avoid infections. However the risk of infection can never be completely eliminated and some patients have a higher risk of acquiring an infection than others.” (6) Therefore it is important to understand the best way to avoid suffering from the infection is by not allowing it to form in the first place. With adequate procedures and a healthy environment, infections such as MRSA can be suppressed.
MRSA can spread from direct skin contact with people and is usually caught from hospitals. Also as the infection is contagious, touching items such as clothes and towels that have been used by someone with MRSA will cause the infection to spread. (13) Although if the person is well and healthy with no exposing wounds, the bacteria is unlikely to do any harm. Preventing these infections from forming in the first place require a lot of attention to detail: •Washing your hands regularly. You may be asked to use an alcohol hand rub when entering and leaving a hospital. •Ensuring all cuts are covered with a waterproof dressing. •Wearing gloves if you are in contact with a person with MRSA. This does not mean if you are just talking to someone though. •Avoid sharing towels, face cloths, etc. with people who have MRSA. (13) “In England, MRSA infection rates in hospitals are falling. Compared with four years ago, the number of MRSA infections has more than halved.” (13) One other reason for this is the use of screening on those attending hospitals. This allows any cases of MRSA in patients to be isolated and identified. This will then allow treatment to be more effective as it will tackle the problem promptly without it causing any further indirect harm.
Implications:
Economic – Costs
MRSA can be a huge problem for the government and health services. The cost associated with dealing with this super-bug is astronomical. When dealing with vancomycin, the following areas are proving costly. Hospitalization
Drug procurement
Preparation and administration
Treating adverse events
Drug monitoring
Treament failure (18)
A study conducted by ‘HERQuLES’ showed that total costs when all costs associated with using vancomycin were included as well as costs from hospital stay were: Skin and soft tissue infections – $23616
Bacteremia – $26446
Infective endocarditis – $48925
Hospital-acquired pneumonia – $22493. (18)
Thus, from this study alone we can say that substantial amounts of money is being invested into tackling the effects of MRSA. But more worryingly this is only the costs of each patient for a single course of treatment. In addition this study does not take into consideration that the drugs developed for MRSA come with numerous side effects, prescribing this and many other antibiotics can lead to possible further treatment being required as the severity of some side effects can be problematic for the patient. Social – Behavioural patterns
A constant drive for maintaining effective antibiotics will lower the risk of an epidemic of MRSA, currently the use of drugs such as vancomycin is possibly preventing the risk of shifts in behavioural activities such as: Food consumption – Society may look to safer sources of food, ones that are more nutritional such as fruit and vegetables. For example raw meat maybe disregarded or much more carefully chosen as they are most likely to carry strains of MRSA pathogens, otherwise the proper use of cooking techniques would be mandatory. Also you would expect the government to tighten up on the storing and general hygiene practice which is carried out before the distribution of these foods, to ensure a safe environment for the processing of these foods. (11) Mass migration of people and transport – As a result of an epidemic you would expect the population of that country affected to instantaneously look for the safest option which is to simply get out of the country. However as a control we are likely to see governments capping down on any form of migration to stop any chances of the epidemic spreading internationally and causing a world crisis. (7) But in reality this is very difficult to achieve.
Human conflict – At a time of on epidemic society will feel much pressured in terms of what they can and cannot do, therefore it is apparent that the government have to maintain complete control and consistency over their rulings. It is the government’s job to implement a fair system for society to follow, otherwise an unjust system that consists of unfair privileges to upper class citizens will escalate conflict and possibly even violence. Tourism – This will take a massive hit for any country suffering from an epidemic of a disease. News of this country will travel fast as we live in such an interconnect world, and tourists will already be making up their minds on whether they want to risk touring a country with a wide spread disease, and of course the answer is likely to be no.
Overall this country would witness a catastrophic effect to an outbreak of MRSA. Also, countries vary in their policies so it is very difficult to implement consistent rulings. For example if one country has many policy’s in place to eradicate the effects of MRSA it is very unfair on them if another country is doing virtually nothing.(7) The problem lies with immigration, in our modern society people are able to fly at ease to almost any country. Thus immigration of migrants between two politically different countries based around their rulings of infections can cause huge problems; bacterial infections such as MRSA are likely to increase. This is why it is very important to detect the infection as quickly as possible before people start migrating to countries without knowing themselves that they are contaminated. Impacts on humans:
Benefits
An immediate impact on society from an effective antibiotic would be that hundreds and thousands of people will remain protected from disease and death each year. Constantly antibiotics have to be developed as without these drugs there is no other way of dealing with patients suffering from MRSA in a mass dimension. So even if the drug is temporary and short term it is still viable for distribution as it would still significantly reduce the infection from spiralling. But more importantly, the absenteeism and general illness/human suffering caused by the symptoms associated with MRSA that can provoke many problems can be suppressed with an effective antibiotic. Fewer individuals will have to be looked after in hospitals, reducing the number of patients and those who have recovered are able to get back to work and indirectly contribute to the economy by increasing the work force and preventing unemployment. Without the presence of these drugs individuals will start to suffer severely and become a further burden for the government in terms of the support they require by the council and the NHS. Risks
MRSA as an infection can clearly be devastating to any human. Directly there are many risks associated with MRSA on a patient, the immediate risk a patient would face is simply death. MRSA being a common bacterium is often carried on the skin, the nostrils and in the throat which can lead to mild infections on the skin, such as impetigo. “If the staph bacteria get into a break in the skin, they can cause life threatening infections such as blood poisoning or even endocarditis”. (3) A more indirect risk of MRSA which I have mentioned above is that MRSA being a bacterial infection can commonly be a problem for a much wider community.
Community – acquired MRSA can often cause infections in previously healthy individuals who would not have witnessed the risk factors a hospitalized patient would. This is why many procedures regarding hygiene are present within a hospital; even minor slip ups can prove to be very costly. (8) Another risk faced by the wider community is that there have been cases in certain countries such as Saudi Arabia where private GP’s have felt pressured due to patients expecting prompt treatment and even an incentive to prescribe as they receive a cut for every prescription. So you could argue that due to extortion or bribery, antibiotics have been distributed unnecessarily and have led to an overuse in an antibiotic. This may cause resistance of the bacteria, raising more problems. (7) Alternatives solutions:
Although antibiotics are constantly being made and are proving to be useful, in order to completely nullify MRSA it would take more than just a drug. Firstly as I’ve mentioned before MRSA is incredibly resistant so eventually it will manage to resist most antibiotics. However in order to control this infection new strategies must be looked at such as the creation of a vaccine or preventing the infection from occurring in the first place. Vaccination
In these current times the creation of a vaccination against MRSA is in its early stages but the end product looks promising. Researchers from The University of Rochester in New York developed an antibody capable of preventing MRSA from dividing during cell division. (12) “Researchers tested the antibody vaccine prior to the implantation of an MRSA-infected pin to stimulate an infected joint replacement. They monitored the bacterial growth and discovered that the vaccine protected 50% of the implanted pin.”(12) The vaccination works by targeting antibodies at the ‘zipper’ of the cell walls. This ‘zipper’ is responsible for the division of the cell as when it unzips the result is two daughter cells (cells that form during mitosis which are genetically identical to the parent cells). So what the antibodies do is ensure the cells cluster up, preventing normal bacterial cell division. (12) This has its advantages as the creation of an effective vaccine will dramatically reduce the costs associated with tackling MRSA by providing a much more cost-effective way of preventing the infection. Also it provides a more stable and long term solution to the problem. Silver dressings
Metallic silver in the presence of liquid leads to the release of the silver ions which is responsible for its biological activity. “Silver ions are biocidal at very low concentrations due to the ability of microbial cells to absorb and concentrate silver from very dilute solutions.”(20) Once in the cell the silver binds to and denatures the proteins, including DNA and RNA, thus inhibiting cell replication and preventing the infection from applying its full affects. Also it is important that the silver present in a dressing is not released into the wound over a short period of time but slowly over a number of days as this will avoid bolus dosing that could lead to systemic toxicity.
A Meta-analyse done by the American Academy of Dermatalogy conclude that there was some evidence for wound healing based on wound size reduction but no evidence based on complete wound-healing. Although the results aided towards more of a short term solution, long term effects are not yet clear. (18) However this form of therapy is not yet fully understood, currently preparations containing colloidal silver are advertised as ‘health foods’, accompanied by claims of their beneficial effects on clinical disorders ranging from influenza to skin conditions such as cuts and warts. (20) Conclusion
The negative effects of MRSA seem to be improving each year, with new controls being used to limit the progression of this infection. The constant investment in this project has raised awareness and led to advances in facilities ultimately tackling down this super-bug into a state were its much better coped with. Recent work by the likes of Robert Daum have opened unapparent doors to possible vaccinations capable of fighting this bacterium, lucky breaks such as this have proven to be starting points for other experts to build on.(14) However in order for these vaccines to have their full effect, constant funding and innovative partnerships must be a main focus. Mean while maintaining a range of effective antibiotics and awareness around communities is critical for the control of MRSA until a sufficient vaccine is developed.
Bibliography
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