This presentation is about MRSA which is also known a 'superbug.' It consist of information on MRSA,MRSA infection,its genetics,types,symptoms,prevention,research,etc

3. HISTORY
Bacteriologist Professor Patricia Jevons discovers first
Methicillin-resistant Staphylococcus aureas (MRSA) in 1961.
October 2nd 1960 was the day when Professor Patricia Jevons
observed Staphylococcus aureus that was resistant to the
antibiotic Methicillin. This new drug, also known as the
chemical compound BRL 1241, had been published in the British
Medical Journal as a suitable alternative to Penicillin for
resistant strains of Staphylococcus aureus just a month
beforehand (September 3rd 1960).
There was some caution reserved in the publication with
resistance being shown in lower doses of the drug. Shortly after
in February 1961 the British Medical Journal cited Professor
Jevons observation of the resistant pathogen that we now know
as MRSA.
It soon became endemic in UK hospitals and around the
world. Now we are seeing its spread in the wider
community. With much more virulent strains of other
"superbugs" evolving we wonder what the next 50 years will
bring.

4. 50 years ago Margaret Patricia Jevons, of the Public Health
Laboratory Service in Colindale, London, published the
first description of meticillin-resistant Staphylococcus
aureus (MRSA). This serendipitous discovery was not
without controversy. Meticillin, a semi-synthetic penicillin,
was introduced in 1959 to treat penicillinase-producing
Staphylococcus aureus infections, which had emerged
almost as soon as penicillin was first used. There was no
room to add a meticillin disc to the susceptibility-testing
plate so, to save money, susceptibility was tested on the
phage-typing plate. This agarose plate was incubated at
30°C, which was fortunate because the initial MRSA strains
were heterogeneously resistant—ie, most of the MRSA
population could express meticillin resistance only at this
lower temperature. These MRSA had been missed in the
clinical laboratories, where testing was performed at 37°C

5. WHAT IS MRSA ?
 Methicillin-resistant Staphylococcus aureus (MRSA) infection is caused by a
strain of staph bacteria that's become resistant to the antibiotics commonly
used to treat ordinary staph infections.
 Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible
for several difficult-to-treat infections in humans. It is also called oxacillin-resistant
Staphylococcus aureus (ORSA).
 MRSA is any strain of Staphylococcus aureus that has developed, through the
process of natural selection, resistance to beta lactam antibiotics, which include
the penicillin's (methicillin, dicloxacillin, nafcillin, oxacillin, etc.) and
the cephalosporin's.
 Strains unable to resist these antibiotics are classified as methicillin-sensitive
Staphylococcus aureus, or MSSA. The evolution of such resistance
does not cause the organism to be more intrinsically virulent than strains of S.
aureus that have no antibiotic resistance, but resistance does make MRSA
infection more difficult to treat with standard types of antibiotics and thus
more dangerous.

6.  Drug resistance occurs because microbes, such as
staph bacteria, need to reproduce to ensure their
survival. When this ability is threatened, as when
they are exposed to antibiotics, microbes adapt
and evolve to overcome the block to their
reproduction. This can occur naturally, and
microbes become genetically altered in ways which
allow them to survive in the presence of
antimicrobial drugs. However, drug resistance
adaptations can be accelerated by human actions,
particularly by the overuse and inappropriate use
of antibiotics. The escalating use of antimicrobials
in humans, animals, and agriculture is increasing
the problem of drug resistance.

7. HOW DOES
METHICILLIN
RESISTANCE
DEVELOP?

8. Drug resistance occurs because microbes, such as staph bacteria,
need to reproduce to ensure their survival. When this ability is
threatened, as when they are exposed to antibiotics, microbes
adapt and evolve to overcome the block to their reproduction.This
can occur naturally, and microbes become genetically altered in
ways which allow them to survive in the presence of antimicrobial
drugs.
 The staph bacterium continues to evolve and is beginning to show
resistance to additional antibiotics. In 2002 the first staph strains
were found that are resistant to vancomycin, an antibiotic that is
one of the few available treatments used as a last resort against
MRSA. Although vancomycin-resistant staph strains are currently
still quite rare, it is feared that these strains will become more
widespread over time and further reduce the limited number of
antibiotics that are effective against MRSA.

9. GENETICS
Structure of the staphylococcal cassette chromosome mec, with the
recombinase genes complex upstream of the mec complex.
The mec complex contains the mecA gene responsible for β-lactam
resistance in Staphylococcus aureus.
PBP-2- Penicillin binding protein
IS1272 = insertion sequence-like element;ccrA and ccrB = cassette
chromosome recombinase genes A and B that mobilize the mec element;
mecR1 = mec sensor transducer and repressor genes that regulate
production of PBP-2A, which is responsible for β-lactam resistance
IS431 = integrated plasmid that encodes tetracycline resistance;
and orfx = open reading frame in which the mobile elements
(staphylococcal cassette chromosome) are located.

11. Although S. aureus has been causing infections (staph infections) probably as
long as the human race has existed, MRSA has a relatively short history. MRSA
was first noted in 1961, about two years after the antibiotic methicillin was
initially used to treatS. aureus and other infectious bacteria.
The resistance to methicillin was due to a penicillin-binding protein coded for by
a mobile genetic element termed the methicillin-resistant gene (mecA). In
recent years, the gene has continued to evolve so that many MRSA strains are
currently resistant to several different antibiotics such as penicillin, oxacillin,
and amoxicillin(Amoxil, Dispermox, Trimox).
HA-MRSA are often also resistant to tetracycline (Sumycin), erythromycin(E-Mycin,
Eryc, Ery-Tab, PCE, Pediazole, Ilosone), and clindamycin (Cleocin). In
2009, research showed that many antibiotic-resistant genes and toxins are
bundled and transferred together to other bacteria, which speed the
development of toxic and resistant strains of MRSA. S. aureus is sometimes
termed a superbug because of its ability to be resistant to several antibiotics.

13. WHAT IS MRSA INFECTION?
 MRSA is a bacterium that enters
the skin through open wounds to cause septicaemia and is extremely
resistant to most antibiotics. This organism is known for causing skin infections in
addition to many other types of infections. There are other designations in the
scientific literature for these bacteria according to where the bacteria are acquired by
patients, such as community-acquired MRSA (also termed CA-MRSA or CMRSA),
hospital-acquired or health-care-acquired MRSA (also termed HA-MRSA or HMRSA),
or epidemic MRSA (EMRSA).
 Statistical data suggest that as many as 19,000 people per year have died from MRSA in
the U.S.; data supplied by the CDC in 2011 suggest this number has declined by about
54% from 2005 to 2011, in part, because of prevention practices at hospitals and home
care.
 In addition, hospital deaths from MRSA infection have declined by about 9,000 per
year from 2005-2011. However, the CDC recently estimated about 80,000 infections with
11,000 deaths occurred in 2011, but they suggest that a far greater number of minor
infections occurred in both the community and in hospitals.

14. WHAT CAUSES MRSA?
Garden-variety staph are common bacteria that can live in our bodies.
Plenty of healthy people carry staph without being infected by it. In fact,
one third of everybody has staph bacteria in their noses.
But staph can be a problem if it manages to get into the body, often
through a cut.
Once there, it can cause an infection. Staph is one of the most common
causes of skin infections in the U.S. Usually, these are minor and don't
need special treatment. Less often, staph can cause serious problems like
infected wounds or pneumonia.
Staph can usually be treated with antibiotics. But over the decades, some
strains of staph -- like MRSA -- have become resistant to antibiotics that
once destroyed it. MRSA was first discovered in 1961. It's now resistant to
methicillin, amoxicillin, penicillin, oxacillin, and many other antibiotics.
While some antibiotics still work, MRSA is constantly adapting.
Researchers developing new antibiotics are having a tough time keeping
up.

16.  The symptoms of MRSA depend on where you're infected.
Most often, it causes mild infections on the skin, like sores
or boils. But it can also cause more serious skin infections or
infect surgical wounds, the bloodstream, the lungs, or the
urinary tract.
 Though most MRSA infections aren't serious, some can be
life-threatening. Many public health experts are alarmed by
the spread of tough strains of MRSA. Because it's hard to
treat, MRSA is sometimes called a "super bug."

18. Skin and soft tissue MRSA infections
Boils and abscesses
An MRSA skin infection usually first develops as a painful bump or a mark in
the skin that looks like an insect bite. The bacteria often enter the
skin through a cut, graze or a hair follicle. This develops into a painful, pus-filled
swelling (boil).
Some people have additional symptoms, such as a high temperature and a
general feeling of being unwell.
In some cases, MRSA can cause a larger, pus-filled lump to develop
underneath the skin. This is known as an abscess.
Cellulitis
MRSA contracted outside hospitals or care homes (called community-associated
MRSA or CA-MRSA) is much rarer but often causes more
extensive skin infections, including a type of infection called cellulitis.
Cellulitis is a bacterial infection of the deeper layers of skin and the layer of
fat and soft tissues underneath the skin. The main symptom is the
skin suddenly turning red, painful, hot and swollen.

21. Invasive MRSA infections
If the MRSA bacteria penetrate deeper inside your body or into your
blood, they can cause serious infections.
Signs that you may have an invasive infection include:
a high temperature (fever) of 38C (100.4F) or above
chills,a general sense of feeling unwell ,dizziness,confusion,muscular
aches and pain, swelling and tenderness in the affected body part
Invasive MRSA infections can lead to the following conditions:
Blood poisoning (sepsis) - which could lead to septic shock, where your
blood pressure drops to a dangerously low level
Urinary tract infection - infection of the parts of the body used to take
urine out of the body, such as the bladder
Endocarditis- infection of the lining of the heart
Pneumonia - a lung infection
Septic bursitis - inflammation of bursa (small fluid-filled sacs under the
skin) caused by a bacterial infection
Septic arthritis- inflammation of a joint caused by a bacterial infection
Osteomyelitis - a bone infection caused by bacteria

22. DIAGNOSIS

23. DIAGNOSIS
Diagnostic microbiology laboratories and reference laboratories
are key for identifying outbreaks of MRSA. Faster techniques for
identifying and characterizing MRSA have recently been
developed. Normally, the bacterium must be cultured from
blood, urine, sputum, or other body-fluid samples, and in
sufficient quantities to perform confirmatory tests early-on.
Still, because no quick and easy method exists to diagnose
MRSA, initial treatment of the infection is often based upon
'strong suspicion' and techniques by the treating physician;
these include quantitative PCR procedures, which are employed
in clinical laboratories for quickly detecting and identifying
MRSA strains. Another common laboratory test is a rapid latex
agglutination test that detects the PBP2a protein. PBP2a is a
variant penicillin-binding protein that imparts the ability of S.
aureus to be resistant to oxacillin.

24. Fluorescent probe before (left) and after (right)
addition of S. aureus

25. Polymer- and colloid-mediated bioassays

27. Screening Programs

28. Surface sanitizing
UV SANITIZER

29. Hand washing

30. Restriction of Antibiotic use

31. Proper disposal of hospital gowns

32. Isolation

33. Decolonization

34. TREATMENT

35. Both CA-MRSA and HA-MRSA are resistant to traditional anti-staphylococcal
beta-lactam antibiotics, such as cephalexin. CA-MRSA has a
greater spectrum of antimicrobial susceptibility, including to sulfa drugs (like
co-trimoxazole/trimethoprim-sulfamethoxazole),
tetracyclines (like doxycycline and minocycline)
and clindamycin (for osteomyelitis), but the drug of choice for treating CA-MRSA
is now believed to be vancomycin, according to a Henry Ford
Hospital Study. HA-MRSA is resistant even to these antibiotics and often is
susceptible only to vancomycin. Newer drugs, such as linezolid (belonging to
the newer oxazolidinones class) and daptomycin, are effective against both CA-MRSA
and HA-MRSA. The Infectious Disease Society of America recommends
vancomycin, linezolid, or clindamycin (if susceptible) for treating patients with
MRSA pneumonia.
Ceftaroline, a fifth generation cephalosporin, is the first beta-lactam antibiotic
approved in the US to treat MRSA infections (skin and soft tissue or community
acquired pneumonia only).

36.  Vancomycin and teicoplanin are glycopeptide antibiotics used to treat MRSA
infections. Teicoplanin is a structural congener of vancomycin that has a similar
activity spectrum but a longer half-life. Because the oral absorption of vancomycin
and teicoplanin is very low, these agents must be administered intravenously to
control systemic infections. Treatment of MRSA infection with vancomycin can be
complicated, due to its inconvenient route of administration. Moreover, many
clinicians believe that the efficacy of vancomycin against MRSA is inferior to that
of anti-staphylococcal beta-lactam antibiotics against methicillin-susceptible
Staphylococcus aureus (MSSA).
 Several newly discovered strains of MRSA show antibiotic resistance even to
vancomycin and teicoplanin. These new evolutions of the MRSA bacterium have
been dubbed Vancomycin intermediate-resistant Staphylococcus
aureus (VISA).Linezolid, quinupristin/dalfopristin, daptomycin, ceftaroline,
and tigecycline are used to treat more severe infections that do not respond to
glycopeptides such as vancomycin.Current guidelines recommend daptomycin for
VISA bloodstream infections and endocarditis.
 Studies suggest that allicin, a compound found in garlic, may prove to be effective
in the treatment of MRSA.

37. RESEARCH

38. Clinical
It has been reported that maggot therapy to clean out necrotic tissue of MRSA
infection has been successful. Studies in diabetic patients reported significantly
shorter treatment times than those achieved with standard treatments.
Many antibiotics against MRSA are in phase II and phase III clinical trials. e.g.:
Phase III : ceftobiprole, Ceftaroline, Dalbavancin, Telavancin, torezolid, iclaprim etc.
Phase II : nemonoxacin.
Pre-clinical
Phage therapy
An entirely different approach is phage therapy (e.g., at the Eliava
Institute in Georgia). Experimental phage therapy tested in mice had a reported
efficacy against up to 95% of tested Staphylococcus isolates.[
Antibiotics
On May 18, 2006, a report in Nature identified a new antibiotic,
called platensimycin, that had demonstrated successful use against MRSA.
A new class of non-β-lactam antibiotics, oxadiazoles, was reported to be effective
against MRSA infection in mouse models. The mechanisms of oxadiazoles’
antibacterial effect are the inhibition of the penicillin binding protein, PBP2a and
biosynthesis of the bacterial cell wall. It was found to have bactericidal activity
against vancomycin- and linezolid-resistant MRSA and other Gram-positive
bacterial strains.

39.  Natural products
 A 2010 study noted significant antimicrobial action of Ulmo 90 and manuka UMF 25+
honey against several microorganisms, including MRSA. The investigators noted the
superior antimicrobial action of Ulmo 90 honey, and suggested it be investigated
further.A separate 2010 study examined the use of medical-grade honey against several
antibiotic-resistant strains of bacteria, including MRSA. The study concluded that the
antimicrobial action of the honey studied was due to the activity of hydrogen peroxide,
methylglyoxal, and a novel compound named bee defensin-1.
 Ocean-dwelling living sponges produce compounds that may make MRSA more
susceptible to antibiotics.
 Some semi-toxic fungi/mushrooms excrete broad spectrum antibiotics, not all of which
have been fully identified. The psychedelic mushroom Psilocybe semilanceata has been
shown to strongly inhibit the growth of Staphylococcus aureus.An in vitro study showed
that the cannabinoids CBD and CBG powerfully inhibit MRSA, in addition to the
terpenoid pinene which occurs in cannabis.
 Cannabinoids (components of Cannabis sativa),
including cannabidiol (CBD), cannabinol (CBN),
 (CBC), tetrahydrocannabinol (THC) and cannabigerol (CBG), show activity against a
variety of MRSA strains.
 Oakin, an Oak extract, has been shown to start killing MRSA immediately and reaches
99.2% at 6 hours, sustaining that kill rate for 48 hours (max time tested).

41. CONCLUSION

42. MRSA has effected the lives of millions. This sudden development of resistance
of bacteria’s towards antibiotics has become one of the most biggest challenges
for the pharmaceutical industry. Everyday we can see that a new antibiotic is
developed.The people tend to misuse or take up incomplete doses of drugs and
end up developing diseases which require higher dose of drugs to deal with
resistance.
In case of MRSA infection the survival rates are 30-50% and even after
treatment its not so sure whether the infection will stop. We cannot stop but at
least prevent it .
It is very important to maintain proper hygiene and increase awareness about
proper usage of drugs and their doses, avoiding half cooked meat,etc.Even if
some of these steps are taken we can stop the spread of MRSA.A lot of new
techniques have been developed recently hence we can hope to deal with the
drug resistance very soon.
“PREVENTION IS BETTER THAN CURE………”

43. THANKYOU
MADE BY:
ARUNA.MOHAN.DAS