Options for combating multi-resistant Staphylococcus aureus

OPTIONS FOR COMBATING MULTI-RESISTANT STAPHYLOCOCCUS AUREUS
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Options for Combating Multi-Resistant Staphylococcus Aureus
Abstract
It has been noted with concern by researchers, clinicians and medics that powerful bacteria are comfortably not responding to the current available antibiotics. This poses a significant threat to public health to all human races. infections linked to antibiotic resistance has tremendously increased over the years being difficult to treat, costing billion of dollars per year and causing more death than any other diseases.
Staphylococcus aureus is a pathogen within the community and hospital believed to have peacefully coexisted with mankind for years can cause a range of illnesses from minor skin infections for instance pimples, boils to more lethal ones such as meningitis and pneumonia. S. aureus have become resistant to methicilin as well as other β-lactam antibiotics via expression of a foreign body PBP. This bacteria is also resistant to other antibiotics, hence making treatment limited and narrow.
This paper establishes a number of options to combat multi-resistant Staphylococcus aureus which include developing new, ‘mutation busting’, developing new drug, stop usage of a drug then reintroduce it when resistance has fallen, carry more research on resistance mechanisms as screening followed by isolation, surface sanitizing, thorough hand washing, essential oil diffusion, decolonization, education and training, and proper disposal of hospital gowns.
Table of Contents
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Abstract  PAGEREF _Toc272839247 \h
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Introduction  PAGEREF _Toc272839248 \h
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Literature Review  PAGEREF _Toc272839249 \h
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History of the bacteria  PAGEREF _Toc272839250 \h
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Sub-categories of MRSA  PAGEREF _Toc272839251 \h
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MRSA Strains  PAGEREF _Toc272839252 \h
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Spread of MRSA  PAGEREF _Toc272839253 \h
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Statistic on MRSA problem  PAGEREF _Toc272839254 \h
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Antibiotic Resistance (S. aureus)  PAGEREF _Toc272839255 \h
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Consequences of antibiotic resistance  PAGEREF _Toc272839256 \h
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Multi-drug Resistance Saureus  PAGEREF _Toc272839257 \h
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Mechanism of MRSA resistance  PAGEREF _Toc272839258 \h
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Possible ways of arresting the menace  PAGEREF _Toc272839259 \h
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Scientific options  PAGEREF _Toc272839260 \h
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Legal options  PAGEREF _Toc272839261 \h
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Conclusion  PAGEREF _Toc272839262 \h
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References  PAGEREF _Toc272839263 \h
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Appendix 1: List of figures  PAGEREF _Toc272839264 \h
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Appendix 2: List of tables  PAGEREF _Toc272839265 \h
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Appendix 3: Abbreviation List  PAGEREF _Toc272839266 \h
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Introduction
Staphylococcus aureus is in the domain bacteria, kingdom eubacteria, phylum firmicuttes, class bacilli, family staphylococcaceae genus Staphylococcus. It is a facultative anaerobic, Gram positive coccus that is grape like with large round, yellowish colonies. The cell occurs singly and when it divides it forms tetrads. The cell wall is constituted of teichoic acid peptidoglycan. The bacteria are resistant to high salt concentration, low humidity and temperature of as high as 50°C (Taylor & Stapleton 2002). Figure I summarize all the characteristics of S.aureus.
Schaechter et al. (1998) concluded that Staphylococcus a time referred to as ‘staph’ is found in between 25%-30% of adult human population and commonly found in the nasal tract or on the skin. In most cases, S. aureus do not cause diseases but damage to skin as well as other related skin injuries leads to infections ranging from mild to severe ones.
All individuals are at risk of staph infection but newborn, breastfeeding mothers, people with diabetes, vascular diseases, lung diseases and cancer are at higher risk (Ingraham & Caroline 2000). Diseases associated with staph include pimples, abscesses, boils, cellulitis, folliculitis, scalded skin syndrome, these are minor. The life-threatening one includes toxic shock syndrome (TSS), chest pain, meningitis, sepsis, bacteremia, osteomyelitis (Chambers 2001).
It has been noted with concern that the rate of staph infection has been on increase worldwide, for instance; in 2005, there were close to 370,000 methicilin-resistant S. aureus infection in United States of America, this was a ten fold increase from 1993 (Ferber 2003)
According to Hiramatsu et al. (2001), this is attributed to Methicillin resistance Staphylococcus aureus (MRSA) strains of the S. aureus which is resistant to methicilin and β-lactam antibiotic such as penicillin, oxacillin, vancomycin and amoxallin.
According to Avison (2005), antibiotic resistance refers to the ability of a bacterium and other microorganism to survive and continue to reproduce despite the use of antibiotic doses previously believed to efficiently act against them. on this line, a number of scientist have thought that if the situation is not arrested earlier enough, human race can find themselves back to the horrible times of pre-antibiotic era. This is because treatment of Multi Resistant Bacterial Infections (MRBI), masquerades a therapeutic test to the medical society.
Literature Review
History of the bacteria
Enright et al. (2002) brought to light that S. aureus (figure1) was brought to public interest by a surgeon sir Alexander Ogston back in 1880 in Scotland. He came across it in pus while operating on abscesses victim.

Figure 1. Electron micrograph of Staphylococcus aureus. Source Todar, 2008
MRSA as stated previously is a bacteria responsible for a number of infections deemed to be difficult to curb in man. It is also known as Multidrug-resistant Staphylococcus aureus or Oxacillin Staphyloccocus aureus (ORSA). MRSA or ORSA is S. aureus bacteria that are resistant to β-lactam antibiotics such as penicillins and cephalosporins (Weigel et al. 2003).
Before the resistance, introduction of penicillin in 1943 seemed to have solved the problems associated with the bacteria. Seven years later, 40% of hospital S. aureus victims were resistant to penincillin, this rose to 80% by 1960; this caused researchers and medics sleepless nights as they tried looking for how to arrest the situation (Felmingham et al. 2002). According to Zhang et al. (2006), the efforts come up with vancomycin effective in treating staph infection, the joy was short lived as in the recent past there have been strains of S. aureus that is resistant to the antibiotic.
Sub-categories of MRSA
Zuger (2004) suggested that there are two main sub-categories of MRSA this is on the basis on the circumstances surrounding how disease is acquired.
Hospital-Asssociated MRSA (HA-MRSA) mostly occurs in patients that are being treated in healthcare facilities for instance nursing homes, dialysis centers or hospitals. Such settings are attributed to causing severe and lethal infections for example pneumonia and bloodstream infections. The sources of HA-MRSA are those patients who are either carriers and do represent symptoms or those already infected. Transmission is mainly through hands especially those of healthcare workers. It’s worth noting that if the hands are not thoroughly cleaned and sterilized, the bacteteria can be transmitted to other patients through a touch (Zuger 2004).
According to Swierzewski (2008), Community-Associated MRSA often occurs in healthy individuals that within a span of the past one year have not been hospitalized or undergone medical procedures for instance surgery or dialysis among others. The infections are minor and include boils, abscesses. These infections can effectively be treated. Levy (1998) stated that with time, CA-MRSA strain have developed a powerful mechanism against treatment and can spread quickly leading to more severe health complications compared to HA-MRSA.
It was noted with great concern that the negative consequences and serious of CA-MRSA were not given attention that were necessary to curb the spread of the infection. Recent studies especially the one carried out in Texas indicated that more persons were being infected by this type of MRSA compared to HA-MRSA and the infection in which between 1999 and 2001, the infection attributed to CA-MRSA increased by fourteen folds. This made researchers and medical practitioners had sleepless nights as they doubled their efforts in trying to come up with options to curbing the menace (Taylor & Stapleton, 2002)
MRSA Strains
There are several strains of MRSA. These include MRSA15 and MRSA16. The two are the most common in England, the later originated from Kettering England and has been established to be similar to ST6:USA200 that circulates in US and carry SCCmec type II, TSS and enterotoxin a genes. This strain is currently known as MRSA252. MRSA300, ST398 and ATCC700699 are other strains. MRSA14 and MRSA16 are resistant to eryhromycin and ciprofloxacin (Meade & Callahan 2000).
Spread of MRSA
It is important to know how MRSA is spread, so as we can be in a better position of coming up with options that are viable in reduction the MRSA threat. According to CDC, MRSA is spread just like any other staph mainly by being in contact with somebody’s infected skin or using personal items an infected individual has used for instance razor blades, towels and bandages (Weber 2003).
Similarly, vets have in the recent past established that there in no doubting that pets such as dogs, cats and the like are another source from which spread of S. aureus and MRSA occurs (Shiota, 2000)
Schools, gym, changing room for athletes, lockers in schools are spots that MRSA infections can be spread. The factors which are linked to MRSA spread include skin to skin contact, contaminated surfaces, open skin, poor hygiene and living in overpopulated environment (Weber 2003).
Statistic on MRSA problem
Researchers and medics are of the opinion that both HA and CA MRSA are on the rise. Statistics reveal that HA-MRSA is attributed to 20% infections of bloodstream at present and 64% of all staph infections (Smith 2005). Skin and soft tissue complications due to staph has risen up to 77% by 2006 from 34% in 2000, this is from a research done in Texas, Veterans Affairs Hospital (Denys, Koch & Dowzicky 2007).
A survey by Center for Disease Control and Prevention (CDC) between 2004 and 2005 established that out of 16.5 million of U.S population, 9000 showed invasive cases, 1000 died of MRSA infections. 85% of the invasive cases are associated with healthcare of which two-thirds took place outside hospital and healthcare facilities 14% of the cases is attributed to person with no exposure to healthcare while 1% of the cases are not known. On this basis, the researchers generalized that 94,400 in the entire country are infected and close to 19,000 casualties in 2005.
In England, the Office for National Statistics in 2005 linked 1,630 deaths to MRSA and in 2006 1654 deaths were reported and attributed to MRSA, this figures raised concerned considering the fact that in 1993, the deaths associated with MRSA was only 51. Studies have revealed that U.S patients infected with S. aureus stay almost three times on hospital, incur expenses three times and are at risk of dying in hospital five times more than those not infected. Cosgrove et al. (2006) came to a conclusion that MRSA is responsible for the high rates of mortality, Wyllie et al. (2000) reported 34% death rate in span of one month of patients infected by the resistant bacteria strain.
In Figure 2, it is very clear that from back in 1993, there is a tremendous incres of number of infections thanks to S.aureus. The number rose to almost 380,000 infections in 2005 from 8,000 infections in 1993.
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Figure 2. MRSA Infections in United States of America Hospitals, between 1993 and 2005
(Source: Agency for Healthcare Research and Quality, Healthcare Cost and Utilization Project
Infections caused by S. aureus and the site infected)
Bacteria are attributed to causing minor to very serious infections; the minor infections include scalded skin syndrome, boils, pimples, abscesses, and cellulitis. Those categorized as being severe include TSS, meningitis, mastitis, pneumonia, osteomyelitis among others. Symptoms for these infections include among others low blood pressure, skin turn red swollen and very painful, chill and fever as well as pus located in a given infected area of the body (Shiota, 2000).
Table 1. Phenotypic characteristics and virulence factors of S.aureus
No.CharacteristicVirulence factors1Gram positiveSurface protein that promote colonization of tissues2Cluster-forming coccus, non motileLeukocidin, kinases and hyaluronidase promoting bacteria spread. Capsule and protein A are surface factors inhibiting phagocytic engulfing3Non-spore formingCarotenoids and catalase production enhance bacterial survival in phagocytes. Hemolysins. Leukotoxin and leukocidin are membrane damaging toxins lysing eukaryotic cell membranes 4Facultative anaerobeProtein A and coagulase immunological disguises5Catalase and Coagulase positive SEA-G, TSS, ET exotoxins that destroy host tissues6Golden yellow on agarInherent and acquired resistance to antibiotics
Antibiotic Resistance (S. aureus)
By definition antibiotic resistance is the ability of microbial to gallantly survive, thrive and reproduce in presence of antimicrobial doses which were deemed to effectively and efficiently work against the microbial. The phenomenon dates back in 1960 when the fast case of penicillin resistance was reported, this has been documented concerning subsequent antibiotics that came after penicillin such as methcillin (Shiota 2000). This thus meant that such drugs can no longer be used to treat microbial infection, making scientist to look for alternatives.
Bacteria, viruses, fungi and parasites do cause infectious diseases; a number of antibiotics are in place to curb spread of and seriousness of the infections. However, some of these microbes seem to have developed resistance against antibiotics. The causes are largely a natural biological process with greater possibility of human triggering it (Sharma et al., 2005).
It is accepted that use of antibiotic in whatever amount time span not withstanding propels bacteria and the likes to ether die or adapt-selective pressure. On the basis of Darwin’s and Lamarck’s (1990) arguments about genetics, only those that adapt and survive carry with them the gene that enhance resistance and pass it on to their subsequent generations.
Mutation, abnormal multiplication of cell has also been thought to be a cause of bacteria resistance to antibiotics. For instance, drug’s target is mutated and one notable example is mutation of gyrA that encode the essential DNA gyrase usually a target when curbing E. coli using quinolones for instance ciprofloxacin (Hadley, 2004).
In addition chromosomal mutation is attributed to penicillin resistance-gonorrhae. This bacterium mutates the gene that codes a porin protein in the outer membrane; this hinders or blocks transportation of penicillin to the cell-‘vertical evolution’ (Avison, 2005).
The factors which encourage spread of bacterial resistance include their ability to multiply very fast and pass the resistant genes to the next generation, incorrect use of antibiotic (either over dose or under dose) also harness spread of resistance (Chambers, 1997)
It is worth mentioning that vet use of antimicrobials in food edible animals and poultry harnesses resistance. Larger quantities are used to enhance growth; this exposes these animals to more often sub-therapeutic concentration of antibiotics. This use has been attributed to rise in resistance in bacteria such as Salmonella (Moon 2010).
Additionally, high risk of resistance to antimicrobial exist in hospitals where patients that are at higher risk, meet with those already infected leading to cross infections coupled with prolonged use of antibiotic use has led to emergence of very resistant bacteria strains (Zhao, 2001).
Marler (2009) said another important factor which leads to antibiotic resistance is the fact that due advertisement and availability of drugs, patient can administer self treatment. A times, this is not necessary as the situation might be mild, the drug might be a counterfeit hence do not contain the right amount of active drug or even not adequately dosed. It has been observed especially in developing countries that people buy doses and administer till they feel better, there is a possibility of that happening and the pathogen has not been eliminated and full dose not taken, this give room for the bacteria to device way of countering the antibiotic, if successful, they pass the resistance genes to their subsequent generations (Giesbrecht, Kersten & Maidhof, 1998).
Other factors that encourage spread of resistance are; urbanization which is linked to overcrowding and poor hygiene, pollution, change in weather, changes in demographic characteristic, globalization characterized with free movement of people, reoccurrence of old problems such as malaria, TB and finally HIV and AIDS which increases the population of immune compromised individuals susceptible to bacterial infections (Giesbrecht et al. 1998).
Generally, causes of antibiotic resistance can be grouped into three main categories and include bacterial genetics, medical practices and agricultural practices (Avison, 2005)
Consequences of antibiotic resistance
The consequences of bacteria S. aureus being resistant to antibiotics are alarming due to severity infections. Infections usually do not respond to treatment, this lengthens duration of sickness posing the victims to death risks. Infectivity period widens resulting to more and more individual being affected putting at risk human race at risk of acquiring the resistant strain of staph (Chambers, 1997).
It has also been established that antibiotic resistance tremendously increases the cost of treatment. For instance, individuals affected will spend more of their dollars in seeking medical attention. Similarly, due to the fact that the infection is resistant to generation one antibiotics, there is need to come up with generation two and even three drugs to curb the infection, this is always an expensive venture that also results to more toxic drugs. It is alarming that more and more disease causing agents are becoming resistant to treatment-taking us back to post-antibiotic period (Rook & Stanford 1998).
Multi-drug Resistance Saureus
The development of antimicrobial drugs are on the basis of cell wall synthesis, thus they are made in such a way that it hinders the metabolic processes of microbial, in this case bacteria. Initially, the recommended treatment for the bacterium infection was penicillin, later; the bacterium thrived and reproduced in presence of this antibiotic. This is attributive to penicillinase which is an enzyme that with the ability to hews β-lactam ring of the antibiotic penicillin molecule; this makes it ineffective (Bootsma, Diekmann & Bonten, 2005).
Antibiotics such as methicillin, flucloxacillin, dicloxacilli, oxacillin, nafcillin, cloxacilin which are resistant to penicillinase have been developed to counter S. aureus. This was only fruitful for a shorter period of time as resistance to these antibiotics came into play. Then vancomycin was developed and currently alternatives for it are in place to treat MRSA, but it is feared that it effectiveness may not last for long (Berger-Bächi & Tschierske 1998).
Mechanism of MRSA resistance
According to Meade-Callahan (2001) and Avison (2005) there are several methods by which bacteria use to acquire resistance, the three broad ones are mutating the target gene for the antibiotic, denying entrance of antibiotic to target cells, pumping out the antibiotic once they gain entrance into the cell and destroying and or limiting the actions of the antibiotic.
The multi-drug resistance of the S. aureus has been linked to the increase of an enzyme β-lactamase as well as presence of distorted form of Penicillin-bidding proteins 2 (PBP 2) that has a lower affinity and very high speed of mechanism that destroys the bound of various drugs (Rook & Stanford 1998).
Russell et al. (1998) remarked the appearance of a PBP, PBP2a is the main methods by which the bacterium develops resistance to methicillin, this is through the mec operon. The low affinity for β-lactam antibiotics makes the bacteria resistant obviating their clinical intentions. This fostered use of glycopeptides vancomycin.
This antibiotic vancoycin was rendered of no use when glycopeptite resistance mediated by acquisition of vanA gene. This gene has its roots from enterococci and it rules/codes for another enzyme that produces an alternative peptidogycan (Zhao, 2001)
The introduction of the aminoglycoside antibiotic for instance gentamicin and kanamycin were effective till the bacterium developed mechanisms to hinder its effectiveness. Inhabitation of the antibiotic occurred through protonated amine as well as hydroxyl interactions with ribosomal RNA of 30s ribosomal subunit (Song et al. 1987).
The enzyme that changes aminoglycoside renders it useless through convulsion and attach to nucleotide, acetyl and or phosphate moiety to alcohol or amine functional group of the drug (Zhang, Eggleston, Rotimi & Zeckhauser, 2006).By doing this, the charge of the drug is compromised as it reduces the antibiotics ribosomal bidding affinity. In the case of S.aureus, the modifying enzyme well known is Aminoglycoside adenylyltransferase 4IA. [ANT(4’)IA]. This enzyme had the potential of attaching to an adenyl moety to the 4’ hydroxyl group of the aminoglycosides, this problem was overcame by x-ray crystallography (Hamilton-Miller 1995).
Mutation which has been thought to be an unavoidable fact of life plays a major role in multi-drug resistance of the bacterium S. aureus. One notable example of mutation is the chromosomal mutation and is attributed to the high numbers of penicillin resistance. Mutation is aimed at the target gene of the drug, the coding for porin protein. This makes the outer membrane impermeable thus faltering transportation of the antibiotic to the intended cell; scientifically this is termed as vertical evolution (Boucher & Corey 2008).
Another mechanism of resistance is by conjugation transfer of R plasmid-horizontal evolution. This type of plasmid carries genes that encode resistance to antibiotics. The F plasmid contains fertility system necessary for transfer of genes between two cells (Song et al. 1987)
In addition, the bacterium through a group of genetic materials on DNA that carries codes for various factors which make infection from the bacterium very successful and difficult to curb (Ruder 2003). The elements make it possible for the genes to migrate from one bacteria to another and from chromosome to plasmid.
Similarly, the bacterium can just add a chemical group to the antibiotic thus deactivating it, for instance changing the electrical charge of the drug by adding a phosphate group. At times the bacterium bulk itself with an added acetyl group. More interesting is the fact that the bacteria have developed a mechanism that helps pump out drugs once the antibiotic has entered into its cells (Alekshun & Levy 1999).
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Figure 3. Resistance mechanism of bacteria to antibiotics
(Source, BioMed Central Ltd, 2005)
From figure 3, a sensitive and a resistant bacterium are shown. In (a), a sensitive bacterium drug gain entry and attacks the bacterium. In (b), a resistant bacterium case, mutation inhibit effects of the drug, acquisition of R plasmid, enzymatic destruction of the antibiotics, reduced concentration of the antibio...