Methicillin-resistant staphylococcus aureus (MRSA) is a bacterium which has developed resistance to a plethora of antibiotics over the past few decades. It was first discovered in the 1960′s (Flaxman and Griffiths 2004) and since has quickly developed its resistance to these antibiotics, among them are: Vancomycin, Tetracycline, Methicillin, Penicillin, Ciprofloxin and others. The goal of our review is to show alternatives, which may be used in place of or together with these antibiotics and could possibly show implications for future use in health-care settings.

Alternative therapies covered in this review will deal with essential/volatile oils. These oils have been used for hundreds of years by cultures around the globe as a means of sterilization/antiseptic methods. These essential oils have been shown to have remarkable abilities at causing cell death to the MRSA bacteria, and as a result of MRSA having evolved such a strong resistance to these antibiotics previously mentioned, scientist and doctors are seeking these new routes of treatment and have begun laboratory testing. The importance of such research should not go unmentioned… According to Klevens et al. (2007), a study published in JAMA (The Journal of the American Medical Association) almost 94,000 MRSA infections occur in the U.S. each year, out of the 94,000 infections 19,000 end up in death, this is more than the HIV virus.

Nosocomial MRSA:

Nosocomial MRSA is staph aureus which originated in the hospital settings. Many of its victims are post-operative patients who have festering wounds which may be open to leakage, just as well MRSA can be internal from the post operative procedure and set itself up in extremely hazardous places within the body, such as the lungs. Current treatments for such patients vary as a result of the severity of the infection. Vancomycin and Bactrim (a sulfur drug which is excreted through the kidneys) are two typical antibiotics used to treat this invasive bacterium. However, while these drugs have effectiveness on curing the problem of MRSA in these hospital patients, more resistance has grown and there are now forms of VISA (Vancomycin Intermediate Staphylococcus Aureus) and VRSA (Vancomycin Resistant Staphylococcus Aureus). MRSA is restant to all forms of Beta-lactam drugs Onlen et al. (2007), as well as sulfur drugs like Bactrim. Alternatives must be sought with such resistance being built by MRSA.

Community Acquired MRSA:

A very common form of MRSA now has become the community-acquired type. It’s origins are from the nosocomial (hospital) acquired MRSA. It began to seep into communities by patients who brought the infections home with them after procedures were performed on them in the hospital settings. Research has been done on the methods of treatment for Community-acquired MRSA; the form of treatments currently being used as noted by (Flaxman and Griffiths 2004) is Mupirocin ointment, a topical ointment that can be used in the nasal passages to kill off MRSA colonization in patients who are carriers of the bacteria. (Flaxman and Griffiths 2004) note the review of findings for Mupirocin treatment in colonized patients was done in 1998 and since that time MRSA has grown in it’s resistances to Mupirocin nasal ointment. Other treatments for community acquired MRSA are Tetracycline, Vancomycin, Bactrim, and other Beta-lactam or sulfur anti-biotics. However, with resistance growing to all forms of these antibiotics, researchers are finding new ways to combat the MRSA infection via laboratory testing since these current antibiotics are no longer showing the promise they once did. With bacterial resistance on the rise, MRSA infections are quickly becoming a pandemic in communities and health-care settings throughout the world, Braga et al. (2005).

Essential Oils:

Our search for answers has come to a pinnacle with the question: What now? We begin our study of essential oils and their effects on MRSA both independently and synergistically with other anti-biotics.  Particular emphasis on this synergism is with Mupirocin ointment since many staff infections are topical/epidermal infections.

Essential or volatile oils are generally isolated from non-woody plant material through distillation methods (Dorman and Deans 2000).  Many of these oils are said to possess antimicrobial properties, which have been used for generations for anti-septic use.  One in particular, tea tree oil, is said to have a broad-spectrum of antimicrobial activity.

Interestingly enough, essential oils are said to have the remarkable ability to wreck the cellular membrane of E. coli and other bacteria. Cox et al. (2000) references an experiment, (Gustafson et al. 1990), in which tea tree oil was used and revealed to have the ability to cause the cellular membrane to lose materials, this in effect could lead to a release of potassium ions from the cell, causing an inhibition of cellular respiration, and eventually leads to the death of the cell.

Since we now have an understanding of the method by which these oils work, let us remember to take into consideration that MRSA has developed sites in it’s outer cell surface at binding sites which now resist the antibiotics given as treatments: Vancomycin, Tetracycline, etc…

Synergism:

Synergistic reactions have been studied with the use of bee propolis, and pomegranate with Mupirocin nasal ointment.  A synergistic reaction of antibiotics is a reaction of two combined medications coming together to have an overall greater effect than either could have on their own.  Let us start with the research done by Onlen et al. (2007) that dealt with propolis, and Mupirocin in synergism together against MRSA.  Propolis is a compound made by bees from tree buds and mixed with secreted bees wax Onlen et al (2007).  In their study of propolis + Mupirocin Onlen et al. (2007, Fig. 1) showed a significant reduction in the colonies of MRSA bacteria in the nasal passages of rabbits compared to that of the Mupirocin group or Propolis group. From the results of Onlen et al. (2007) evidence for the possible future use of an alternative form of treatment for MRSA was confirmed.

Another study conducted by Braga et al. (2005), which was published in the Canadian Journal of Microbiology, sought the antibacterial affects of pomegranate extract with a list of selected antibiotics.  These antibiotics included tetracycline, chloramphenicol, oxacillin, gentamicin, and ampicillin.  Pomegranate extract did not produce enough evidence on it’s on to show a significant reduction in the bacteria. When combined with the various beta-lactam drugs used in the experiment, pomegranate did show considerable activity against MRSA Braga et al. (2005).  However, the effect with pomegranate and gentamicin was not as significant.  Pomegranate in this study showed an interesting characteristic that could be correlated with the actions of tee tree oil.  Both extracts worked on a cellular level to cause inhibition of some sort.  Pomegranate acted in such a way as to function as an efflux pump blocker; the cells ability to intake antibiotics was increased as well. Braga et al. (2005).

Essential oils without synergistic methods:

Thus far we have seen the effects of synergism in bee propolis and pomegranate.  Essential oils however, do not only show activity against Staph. Aureus when used in antibiotic compounds, but also when used by themselves.  One such study carried out by Ugur et al. (2005) was for the antibacterial activity of Ironwort (Sideritis curvidens and Sideritis lanata).  This essential oil, which was extracted from the plant, showed strong activity against the form S. aureus resistant to several forms of antibiotics Ugur et al. (2005, Table 2).  The antibiotics used in this experiment however lacked the significant inhibition effects that the volatile oils had on the bacteria.

One study, published in the Journal of Pharmaceutical Biology, written by Hoffman et al. (2004) was conducted on ten plants; of the ten plants used in the experiment five had activity against MRSA. These five plants are (Phyllanthus niruri, Ageratum conyzoides, Acanthospermum hispidum, Sida acuta, Cassia alata).  In Hoffman et al. (2004, Table 1) zones of inhibition are given and measured in (mm).   Phyllanthus niruri had the largest zone of inhibition consisting of a 24.3(mm) diameter which was correlated with the QC (Ciprofloxin group) which had a ZOI of 27.9 (mm).  This provides further evidence to show essential oils may have an important role in the future of health-care settings with MRSA related incidents.

Though many plant extracts made into essential oils can be used for antibacterial or antimicrobial activity not all can be used. Took 120 plant species for extraction of essential oils, of the 120 plants 81 extracts were obtained, 51 extracts showed signs of activity against MRSA Nascimento et al. (2000).  In the study of Nascimento et al. (2000) a table is given, Nascimento et al. (2000, Table 1), which shows the activity of 10 different plants used in their experiment.  Of the ten plants tested only one gave signs of inhibition of Staph. aureus; jambolan showed this inhibition.  This study should be correlated with the study by Braga et al. (2005) that used pomegranate as an antimicrobial agent, which showed signs of activity against MRSA.  One study said pomegranate showed no signs of inhibition, Nascimento et al. (2000), while Braga et al. (2005) did show signs of activity.  This could be due to experimental error or perhaps a larger quantity was used for the extract in the experiment of Nascimento et al (2005).

Conclusion:

In conclusion, essential oils may play a significant roll in the inhibition of MRSA in both nosocomial and community acquired settings. This leads many researchers to believe that they may play a very important role in the future treatment of this particular pathogen along with other bacterial resistant strains as well.   Though this study showed bee propolis and pomegranate to work synergistically with Mupirocin, MRSA is increasing in its resistance to Mupirocin slightly.  This begs the question that the use of the two substances together could lead to MRSA becoming resistant to volatile oils, when so far in these studies very few have shown little resistance to their inhibiting effects on MRSA.  However, the possibility remains that MRSA could likely become resistant to volatile oils if it’s cellular structure adapts to form a mechanism within the cell to slow or stop potassium ion leakage caused by certain oils like tea tree oil that lead to cell death.

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Primary Sources Cited:

1.    L.C. Braga, A.A.M. Leite, K.G.S. Xavier, J.A. Takahashi, M.P. Bemquerer, E.Chartone-Souza, and A.M.A. Nascimento.  Synergic interaction between pomegranate extract and antibiotics against Staphylococcus aureus. Can. J. Microbiol. 2005; 51: 541-547

2.    Yusuf Onlen, M.D., Nizami duran, Ph.D., Esin Atik, M.D., Lutfu Savas, M.D., Enes Altug, Ph.D., Selvinaz Yakan, Ms.C., and Ozkan Aslantas, Ph.D. Antibacterial Activity of Propolis Against MRSA and Synergism with Topical Mupirocin.  The Journal of Alternative and Complementary Medicine. 2007; Vol 13: 713-718.

3.    A. Ugur, O. Varol, and O. Ceylan.  Antibacterial Activity of Sideritis curvidens and Sideritis lanata from Turkey.  Pharmaceutical Biology. 2005; 43: (1): 47-52

4.    Lutfu SAVAS, Nizami, Duran, Yusuf Onlen, Nasan Savas, Mustafa Erayman.  Porspective Analysis of Antibiotic Susceptibility Patterns of MRSA in a Turkish University Hospital.  Turk. J. Med. Sci.  2005; 35: 323-327

5.    Gislene G.F. Nascimento; Juliana Locatelli; Paulo C. Freitas; Giuliana L. Silva.  Antibacterial activity of plant extracts and phytochemicals on antibiotic-resistant bacteria.  Brazilian Journal of Microbiology.  2000; 31: 247-256

6.    H.J.D. Dorman and S.G. Deans.  Antimicrobial agents from plants: antibacterial activity of plant volatile oils.  Journal of Applied Microbiology.  2000; 88: 308-316

7.    B.R. Hoffman, H. DelasAlas, K. Blanco, N. Wiederhold, R.E. Lewis, L. Williams.  Screening of Antibacterial and Antifungal Activities of Ten Medicinal Plants from Ghana.  Pharmaceutical Biology. 2004; 41 (1): 13-17

8.    Debora Flaxman, Peter Griffiths.  Is tea tree oil effective at eradicating MRSA colonization? A review.  British Journal of Community Nursing 2004; 10 (3): 123-126

9.    S.D. Cox, C.M. Mann, J.L. Markham, H.C. Bell, J.E. Gustafson, J.R. Warmington and S.G. Wyllie.  The mode of antimicrobial action of the essential oil of Melaleuca alternifolia (tea tree oil).  Journal of Applied Microbiology.  2000; 88: 170-175

10.    Jafer Adinee, Khosro Piri and Omid Karami.  Essential Oil Component in Flower of Lemon Balm (Melissa officinalis L.)  American Journal of Biochemistry and Biotechnology 2008; 4 (3) : 277-278

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If you have read the “about our blog” section then you will have no doubt run across the “primary and secondary” sources part we said we would use in our posts.  To clear things up for those of you who have asked, what is a primary or secondary source?

Below we have described them for you…

Primary Sources:

Primary sources in the case of our site and posts are sources of scientific or medical research which have been tested by scientist through lab experimentation and rigorous work.  Primary literature will have following format:

• Abstract (short summary at the beginning of the paper)
• Introduction (why the scientist(s) is pursuing the given experiment and it’s importance)
• Materials and Methods (what the scientist(s) use during their experiment and the measure they take)
• Results and Discussion (results given in favor or not in favor of the hypotheses and why)
• Conclusion (conclusions based on evidence in study)
• References (literature cited section)
• Acknowledgments

Primary resources contain technical information and is geared towards a specific professional audience in most cases.  Within the literature the reader will find measurements, graphs, tables, randomization procedures, etc.

Secondary Sources:

Secondary sources are professional journals and magazines which derive their information from primary sources.  Some good examples of secondary sources would be National Geographic, and Scientific America.  Secondary sources are one step away from primary sources.  The secondary source can include

• Pictures
• Graphs
• Tables
• Quotes

Generally you will not find a professional secondary source quoting a primary, rather they will give a reference to the material which was researched. On rare occasion quotes will be used. The use of references — rather than quotes — shows that the writer has a good background on the subject, has comprehended it’s material fully, and is able to form his/her own thoughts on the subject rather than quoting the author. Secondary sources are also broken down into simpler terms for people not so interested in the technical jargon, so the average Joe can understand it.

The job of the secondary source is to research and review the findings of primary sources.