Methicillin-resistant Staphlococcus aureus Strain ST398
Felicia M. Lamb
Abstract
Methocillin-resistant
Staphlococcus aureus (MRSA) is a
virulent bacteria which affects human health in multiple pathways. MRSA has
been a direct result of improper antibiotic use over several decades. The resistances built by bacteria are
directly impacting our healthcare system locally and on a global scale. MRSA
has several strains that have developed as a result of mutating genes, but the
strain ST398 has been reported to travel from pigs to humans and is of
particular interest. Specifically, ST398 has the ability to jump species lines,
which can cause extreme adverse effects in select populations. This review
paper will discuss the affect of MRSA on human health, its vectors,
transmission, and current modes of treatment. The goal is to synthesize the
most current information in order to promote better health education.
Keywords:
Methocillin-resistant Staphlococcus
aureus, ST398, antibiotic resistance,
livestock
Methicillin-resistant Staphlococcus
aureus Strain ST398
Antibiotic resistance has
become an ever-increasing issue in the healthcare world. Resistance has been a
result of improper antibiotic use in humans and also in livestock. The use of antibiotic therapy in
livestock has primarily been as a growth promotion agent, which means the
antibiotic is not dosed at therapeutic levels, opening the door for resistances
to develop. Stuart Levy pointed
out in his 2010 book The Antibiotic Paradox,
second edition, that “food livestock animals outnumber humans in the United
States more than five to one” (p. 149).
This is an important number when considering that the majority of the
food livestock in the U.S. are on subtherapeutic levels of antibiotic for
growth promotion. Levy also claimed,
in The Antibiotic Paradox, that “sub-therapeutic
usage is four to five times greater than the amount used for treatment of
animal disease” (p. 149). This use
of antibiotics is careless and without regard for future ramifications. Antibiotics have a long history of
being referred to as miracle drugs, but deliberate disrespect for their
limitations is causing more harm than good. The complications caused by the careless use of antibiotics are clear in in the case of Staphlococcus aureus, which has evolved genetically to resist several
antibiotics leading to a newly discovered bacteria we now refer to as
Methicillin-resistant Staphlococcus
aureus or MRSA.
Methocillin-resistant Staphlococcus aureus has received extra attention recently due to its ability to mutate, resulting in several different strains (clones) of the same bacteria. MRSA has numerous clones that have developed since the introduction of antibiotics, so an exact number of clones has not been determined (Enright et al., 2002). Flaxmann and Griffiths stated in their 2004 literature review that “MRSA has been reported as early as the 1960s. However, it has gone from being a rare occurrence to being recognized as one of the leading global nosocomial [illness acquired while in a hospital] pathogens” (p.123). The complications with MRSA infections come not only with disease infections, but also with carriers of the disease, which can extend outside of humans to livestock vectors (Flaxmann and Griffiths, 2004).
This paper reflects the topic of
methicillin-resistant Staphlococcus
aureus clone ST398 and its effect on the pig livestock industry and human
health. The background section will bring
forward the history of MRSA resistance development, demonstrated capabilities
of transferring through species lines, impact upon human health, and the search
for effective treatments for those individuals affected by MRSA complicated
disease. Based upon the evidence
presented, conclusions will be drawn on the future of antibiotics with specific
consideration for MRSA.
Background
The evolution of knowledge
on bacteria infections dates back to 400 BC when Hippocrates wrote the book On Air, Waters, and Places, in whichhe
analyzed disease and its capability to spread. Hundreds of years later, Florence Nightingale took it a step
further when she recognized, described, and spoke about the spread of disease (Stirling
et al., 2004). Over a century
later, the bacterium we now call methocillin-resistant Staphlococcus aureus was discovered.
“Methocillin-resistant Staphlococcus aureus (MRSA) infection is
caused by a strain of staph bacteria that has become resistant to the
antibiotics commonly used to treat ordinary staph infections” (Mayo Clinic
Staff, 2010, para. 1). MRSA became
a significant problem about 50 years ago, when the standard treatments for
regular staph infections were no longer effective. Since the standard treatments where found unreliable, a
simple staph infection became a major, sometimes life-threatening problem. In the early 1980s, MRSA was discovered
not be a new more virulent microorganism that was causing problems, but instead
Staphlococcus aureus had mutated over
time to its surroundings. It had
developed resistances to methicillin and to other antibiotics. These resistances have developed from
decades of improper antibiotic use.
Doctors have prescribed antibiotics in recent decades for the common
cold and flu, viruses that do not respond to antibiotics. Additionally, the agricultural use of
antibiotics at non-therapeutic levels for growth promotion have been isolated
as the culprit of Staphlococcus aureus
resistances. Stirling et al. (2004) explained that resistances
develop because “pathogens are
constantly adapting to their environment as it changes; with the improper use
of antibiotics, weaker bacteria are killed, but stronger, more resilient ones
live on and reproduce (p.19).” Common
cold, influenza, and other viruses do not respond to antibiotics, and unnecessary
treatment gives the healthy bacteria living on or in the body a chance to adapt
to their surrounding by creating resistances to the antibiotic causing
opportunistic infections. The over-prescribing
of causeless antibiotics, or use at non-therapeutic levels for growth in
livestock, is unequivocally the cause of MRSA.
Because of the global prevalence of methocillin-resistant Staphlococcus aureus, scientists have been actively searching for answers that will lead to effective prevention and treatment of the disease.
There are two separate evolutionary pathways of MRSA that are commonly discussed in scientific literature: methocillin-resistant Staphlococcus aureus community-acquired (CA-MRSA) and methocillin-resistant Staphlococcus aureus hospital-acquired (HA-MRSA) (Wulf et al., 2008). These two types of MRSA are classified according to the location where the patient was originally infected, i.e., in the community or in a hospital. Each is spread through different routes; the CA-MRSA is typically transmitted by skin-to-skin contact, whereas HA-MRSA infection travels by invasive procedures, intravenous tubing or artificial joints (Mayo Clinic Staff, 2010). Since MRSA’s original classification, both CA and HA strains have crossed into each other’s areas making it more difficult to treat the infections, as both require different treatments.
Organisms with the
capability to reinvent themselves are particularly intriguing. The recent discovery of ST398 strain has
shown that it is genetically unrelated to CA-MRSA and HA-MRSA. In addition, the ST398 strain has been
found to be resistant to digestion by the enzyme Sma1 (Denis et al., 2009), enhancing its ability to proliferate in
the body.
Bacteria adapt to their surroundings by mutating in their DNA sequence to avoid or resist the antibiotics present in their environment. Velebit et al. in 2009 discovered that MRSA is not only resistant to methicillin, but also other antibiotic treatments such as oxacillin, ciprofloxin, and clindamycin (Velebit et al., 2009). Tenhagan et al. added to the list of resistant antibiotics in his 2009 work including tetracycline, erythromycin, gentamicin, and kanamycin (Tenhagen et al., 2009). Also in 2009, Wulf et.al found that 58% of ST398 MRSA is multi-resistant, which means the bacteria carry resistances to five or more classes of antibiotics. This information supports the findings of Velebit et al. and Tenhagen et al.
Because of the discovery
of strain ST398, it is important to look more closely at its relevance to
humans.
ST398 in Pigs and Humans
The new strain of MRSA,
ST398, was discovered in the Netherlands in pigs and humans five years ago, and
now the same strain, MRSA ST398, has been discovered in many countries
including the United States (Mckenna, 2009). The strain has been tracked from Europe to North America
with the original identification in North America occurring in Ontario, Canada. Since then, swine farms in Iowa and Illinois
have had 70% of their pigs testing positive for ST398 along with nine of the
fourteen workers tested (Mckenna, 2009).
The concerning detail about ST398 is that it can readily transfer from
pigs to humans. Pig farmers are at
the highest risk for contracting ST398, while other high risk groups are people
living in pig farming communities, slaughterhouse workers, and veterinarians (Mckenna,
2009). The origin of MRSA in pigs
has not yet been found, but leading theories indicate that it comes from the
trade between countries of live animals and the use of non-therapeutic levels
of antibiotics for growth promotion (Mckenna, 2009).
The ST398 bug is carried in
the nostrils of pigs causing no direct harm to the pigs, but after transferring
to humans it causes major medical complications which can be life threatening. There are many spa genes, or subtypes,
of the multilocus sequence type ST398 (t011, t034, t108, t539, t1739) (Pomba et
al., 2009) (t567, t571) (Wulf et al., 2008). The different spa types are being identified as having
slight variation of the same strain of MRSA ST398, where each carrying their
own set of resistances. Still, all
of the spa types include the original resistance methicillin.
ST398 in pigs. Staphlococcus aureus has been a known bacteria that pigs harbor, but it
was only recently that these animals were known to carry MRSA strain
ST398. Surprisingly, ST398 was
found to commute from pigs to humans (Ferber, 2010). Dan Ferber stated in 2010 that ST398 has not been known to
transfer between humans, and the infection is isolated to contact with pigs
which should keep ST398 from becoming a broad community epidemic.
ST398 in humans. Humans carrying ST398 have been reported in higher numbers since the original
discovery. Pig farmers have a high
incidence of being carriers of ST398, which is an expected outcome because
ST398 is transferred from pigs to humans who have direct contact. Van Cleef et al. concluded in 2010 that
working with live pigs is the single most important factor for being MRSA positive. The CDC has described MRSA ST398 as
being pathogenic to humans. A “search
and destroy” policy that The Netherlands implemented shortly after the ST398
outbreaks started appearing in hospitals around the country has been successful
at keeping the MRSA rates at 1% (Wulf et al., 2008). This policy is designed to protect others from contracting MRSA by
mandating that all people who are in contact with pigs are isolated and
screened upon admission to the hospital.
The policy has been successful in the Netherlands thus far and should be
considered on a global human health level to reduce or eliminate the
pathogenicity of MRSA. Current
measures taken for disease control of MRSA in the United States have not been
as successful as what has been witnessed in the Netherlands.
The likely carriers of ST398
are not only workers on swine farms, but also veterinarians, and slaughterhouse
workers. In one study, it was
found that 5-6% of slaughterhouse workers carried MRSA in their nostrils. The infected individuals were found to
be exclusively those having contact with live pigs (Van Cleef et al., 2010). It has been found that working with
dead pigs does not appear to carry the same risk factors as working with the
live animals. Van Cleef summarized
it simply in 2010 that “ultimately, working with live pigs is the most
important determinate for nasal ST398 carriage” p.756.
Treatment
Treatment of MRSA has been
difficult from the onset. The overriding difficulty arises from the reality
that MRSA is a bug that has the ability to recognize something in its environment
that is less than desirable and instead of allowing the foreign object to kill
it, undergoes mutation thereby adapting to the foreign object, and associated
antibiotic treatment. The result
has been the development of antibiotic resistance(s). In 2005, Sharpe et al.
elucidated that “vancomycin historically has been the treatment of choice
for MRSA infections, but adverse effects, the need for intravenous access, and
growing resistance limit its use” (p. 425). Linezolid has been an effective treatment, and has been more
desirable simply because it comes in an oral formulation. Also, linezolid has been the pick over
vancomycin because even though it is a more costly drug, at $117/day more than
vancomycin, it also shortened the patient’s hospital stay by 3 days, and
estimated $6,438 in hospital charges (Sharpe et al., 2005).
Developing treatment. A new beta-lactams, broad-spectrum cephalosporins and one carbapenem, are in development stages currently as a new treatment for MRSA (Page, 2006). Ceftabiprolle midocaril, the most effective cephalosporin against MRSA was developed in 2006; its target is primarily skin and soft tissue infections (Page, 2006). The cephalosporin PPI-0903 has also been developed recently, covering a range of gram-positive and gram-negative bacteria, where the gram-positive properties are able to cover MRSA, accounting for its excellent bacterial coverage (Page, 2006). Initial testing indicates that ceftobriprole medocaril has therapeutic activity against MRSA, still ceftobriprole medocaril is in the clinical trial phase of its development.
Another antibiotic that has been developed in recent years but has not had quite the efficacy as others is carbapenem RO4908643, this antibiotic has similar effects as imipenems and meropenems. According to Page in 2006, RO4908643 was still in the testing phase of the therapeutic effects, investigation is ongoing regarding this drug.
Several other cephalosporins are
being developed and tested for the effects against MRSA, but their development
has been less than impressive thus far. Another study indicated that
teicoplanin is the drug of choice for MRSA meningitis and has efficacy similar
to vancomycin, additionally it does not present as many side effects as
vancomycin (Sipahi et al., 2005).
Organic treatment. Treatment of the organic
fashion is incorporated with the tea tree oil derived from Australia. Tea tree oil has been used by Aborigines
for thousands of years as an antiseptic. Now it has a reputation for being used
as a shampoo but at the correct concentration the active ingredient terpinen-4-ol
has been found to kill MRSA (Flaxmann and Griffiths, 2004). This data needs further supporting
research, but lends an interesting path to future treatment with very few, if
any, side effects.
Conclusion
Understanding disease, its
transmission, how resistances are developed and effective treatment are vital
to the medical practice. Stirling
et al. defined in 2004 that “infectious disease transmission requires three
components: an agent, a vulnerable host and a conducive environment” (p.17). In the case with MRSA ST398 the agent
is pigs, vulnerable host is the family and employees, and the environment is
the swine farm operations, and slaughterhouses. MRSA ST398 has a tendency to
cause infections in not only immune compromised people, but also healthy people.
The need for stronger antibiotics is increasing for the proper treatment of
this disease, which leads to limited future treatment. The propagation of these virulent
strains has been a result of overuse of antibiotics, and evolution in the
bacteria. The Netherlands have
been using the search and destroy methodology, where everyone who comes into
the hospital is tested and isolated to combat the spread of MRSA. This strategy of isolation has had
great success, indicating that this system should be implemented elsewhere,
possibly worldwide (Van Den Broak et al., 2009).
MRSA ST398 levels have
dramatically increased in the last few years, to a point which borders on worldwide
epidemic as it has been reported in Italy, Thailand (Wulf et al., 2008), Japan
(Enright et al., 2002), Serbia (Velebit et al., 2010), Portugal (Pomba et al.,
2009), Belgium (Denis et al., 2009) Denmark, The Netherlands, Germany, Canada,
and the United States (Ferber, 2010). MRSA has become recognized as a major
health concern globally and ultimately is responsible for considerable
mortality, not to mention the significant investment in treatment leading to an
increase in the cost to our healthcare systems. As antibiotics have saved limitless lives, we need to
respect their boundaries if the medical practice is going to be able to use
them in the generations to come.
References
Denis, O., Swetens, C., Hallin, M., Catry, B.,
Ramboer, I., Dispas, M., Willems, G., Gordts, B., Butaye, P., Struekens, M. J.
(2009). Methicillin Resistant Staphlococcus
aureus ST398 in swine farm personnel, Belgium. Emerging Infectious Diseases, 15(7), 1098-1101. doi:
10.3201/eid1507.080652
Enright, M. C., Robinson, D. A., Randle, G., Edward,
J. F., Grundmann, H., Spratt, B. G. (2002). The evolutionary history of methicillin-resistance Staphlococcus aureus (MRSA). The National Academy of Sciences, 99(11),
7687-7682.
doi: 10.1073/pnas.122108599
Ferber, D. (2010). From pigs to people: The emergence of a new superbug. Science, 329-5995, 1010-1011. doi: 10.1126/science.329.5995.1010
Flaxman, D., Griffiths, P. (n.d.). Is tea tree oil
effective at eradicating MRSA colonization? A review. British Journal of
Community Nursing, 10(3), 123-126.
Levy, S. B., (2010). The antibiotic paradox how the misuse of antibiotics destroys their
curative power second edition. Cambridge, MA: Perseus Publishing
Mayo Clinic Staff (2010). MRSA infection. Mayo Clinic. Retrieved from http://www/mayoclinic.com/health/mrsa/DS00735
Mckenna, M. (2009). A new strain of drug-resistant staph infection in U.S. pigs.
Scientific American. Retrieved from http://scientificamerican.com/article.cfm?id=new-drug-resistance-mrsa-in-pigs
Page, M. G. P. (2006). Anti-MRSA beta-lactams in
development. Current Opinion in
Pharmacology, 6, 480-485. doi: 10.1016/j.coph.2006.06.002
Pomba, C., Henrik, H., Cavaco, L. M., Diniz de
Franseca, J., Aarestrup, F. M. (2009). First description of
methicillin-resistant Staphlococcus
aureus (MRSA) CC30 and CC398 from swine in Portugal. International Journal of Antimicrobial Agents, 34, 181-195. doi:
10.1016/j.ijantimicag.2009.02.019
Sharpe, J. N., Shively, E. H., Polk Jr., H. C.,
(2005). Clinical and economic outcomes of oral linezolid versus intravenous
vancomycin in the treatment of MRSA-complicated, lower extremity skin and
soft-tissue infections casue by methicillin-resistant Staphlococcus aureus. The American Journal of Surgery. 189,
425-428. doi: 10.1016/j.amjsurg.2005.01.011
Sipahi, O. R., Arda, B., Yurtseven, T., Sipahi, H.,
Ozgiray, E., Suntur, B. M., Ulusay, S. (2005). Vancomycin versus teicoplanin in
the therapy of experimental methicillin-resistant Staphlococcus aureus (MRSA) meningitis. International Journal of Antimicrobial agents, 26, 421-415. doi:
10.1016/j.ijantimicag.2005.08.011
Stirling, B., Littlejohn, P., Willband, M. L. (2004).
Nurses and the control of infectious diseases. Canadian Nurse, 100(9), 17-20
Tenhagen, B-A., Fetsch, A., Stuhrenberg, B.,
Schleuter, G., Guerra, B., Hammerl, J. A., Hertwig, S., Kowall, J., Kampe, J.,
Schroeter, A., Braunig, J., Kasbohner, A., Appel, B. (2009). Prevalance of MRSA
types in slaughter pigs in different German abattoirs. Veterinary Record, 165, 589-593. doi: 10.1136/vr.165.20.589
van Belkum, A., Melles, D. C., Peeters, J. K., van
Leeuwan, W. B., van Dulnkeren, E., Huijsdens, X. W., Spalburg, El, de Neeling,
A. J., Verbrugh, H. A. (2008).
Methiciilin-resistance and susceptible Staphlococcus aureus sequence type 398 in Pigs and Humans. Emerging Infectious Diseases, 14(3),
479-483. Retrieved from www.cdc.gov/eid
van Cleef, B.A.G.L., Broens, E.M., Voss, A.,
Huijsdeus, X.W., Zuchner, L., van Benthem, B.H.B., Kluytmans, J.A.J.W.,
Mulders, M.N., van de Giessen, A.W. (2010). High prevalence of nasal MRSA
carriage in slaughterhouse workers in contact with live pigs in The
Netherlands. Epidemiology and Infection,
138, 756-763. doi: 10.1017/S0950268810000245
van den Broek, I.V.F., Van Cleef, B.A.G.L., Haenen,
A., Broens, E.M., Van der Wolf, P.J., Van den Broek, M.J.M., Huijsdens, X.W.,
Kluytmans, J.A.J.W., Van de Griessan, A. W., Tiemersma, E.W. (2008).
Methicillin-resistant Staphlococcus aureus
in people living and working in pigs farms. Epidemiology
and Infection, 137, 700-708. doi: 10.1017/S0950268808001507
Velebit, B., Fetsch, A., Milorad, M., et al. (2010).
MRSA in pigs in Serbia. Veterinary Record,
167, 183-184. doi: 10.1136/vr.c3757
Wulf, M.W.H., Sorum, C., Hallin, M., Catry, B.,
Ramber, I., Dispad, M., Wilems, G., Gordts, B., Butaye, P., Struelens, M.J.
(2009). Methicillin Resistant Staphlococcus
aureus among veterinarians: an international study. Clinical Microbiology and Infection. 14, 29-34.
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