mrsa

JAYSHREEPh.D SCHOLAR

Staphylococus aureus

Gram Positive

Non-motile

Spherical

Grows in clumps

Resembles clumps of grapes

Golden color- colonies

Some produce hemolysis

Some produces coagulase

Produce catalase enzymes

Virulence Determinants of Staphylococcus aureus

Frequency of Staphylococcus aureuscolonization in carriers on various body sites

Nose 100%

Skin chest 45%

Perineum 60%Ankle 10%

Axilla 19%

Hand 90%

Forearm 45%

4

S. aureus – as pathogen

• virulent factors (toxins and enzymes)

• Frequent nosocomial- and community-acquired pathogen

• Mode of transmission –contact

• Clinical manifestations1/31/2015 5

Superficial Infections

Scalded Skin Syndrome: Classic Toxic Shock

Systemic Menstrual Toxic Shock

Cont…

• The Staphyloccoccus aureus bacterium,

commonly known as staph, was discovered in

the 1880s - painful skin and soft tissue

conditions

• Initially cases were treated by draining the

abscess or boil

Cont…

• In the 1940s, medical treatment for S.aureus infections became routine asPenicillin was introduced as drug of choice.

• Penicillin- bacterial cell wall synthesis- inflow

of water- cell burst

Cont…

• But resistance to penicillin in Staph. aureus -

due to the presence of penicillinases in them.

• Later on due to development of resistance to

penicillin

Cont…..

• In 1959 methicillin was introduced for Staph.

aureus resistant to penicillinases (Leonard and

Markey, 2008)

• In recent time resistance leading to use of

vancomycin.

Cont..

• Most strains of MRSA are inhibited by

concentrations of vancomycin ranging from

0.5- 2.0 mcg/mL, although strains have been

reported with intermediate sensitivity that

have been called Glycopeptide intermediate

staph aureus or Vancomycin intermediate staph

aureus.

What Is MRSA?

• MRSA is the term used for any strain of

Staphylococcus aureus that has developed

resistance to β- lactam antibiotics, which include

the penicillins (methicillins, oxacillin,

dicloxacillin etc.) and cephalosporins

• MRSA causes a variety of disseminated, lethal

infections in humans.

• Has the ability to easily transfer resistant genes to

other species directly and indirectly

•Resistance of MRSA to β- lactam antibiotics including

penicillinase stable β- lactam is mediated by the mecA gene.

•This gene is expressed in bacterial cell wall and encodes

for a penicillin binding protein (PBP2a) which has a low

affinity for β- lactam antibiotics (Leonard and Markey, 2008).

•SCCmec element is a genomic island of unknown origin

containing this antibiotic resistant mecA gene (Batabyal et al.,

2012).

how MRSA is resistant to methicillin?

How “Tough” is MRSA?

• Staphylococci can survive many extremeenvironmental conditions.

• The bacteria can be cultured from dried clinicalmaterial after several months, are relatively heatresistant, and can tolerate high salt media.

So, “What Do we Do?”

• You can not get rid of MRSA; you can onlycontrol it.

How is MRSA spread?

1. Direct contact with infected or colonized host -human-to-human contact

2. Contaminated intermediate surfaces

-hand towels

-faucets

-tub/shower

3. Airborne fluid droplets

CA-MRSA and HA-MRSA

CA-MRSAUniquemicrobiologic andgenetic propertiescompared withHA-MRSA mayallow thecommunity strainsto spread moreeasily or causemore skin disease

Community-Associated (CA)-MRSA

• CA-MRSA has only been known since the

1990s.

• CA-MRSA is of great concern to public health

professionals because of who it can affect.

• CA-MRSA skin infections are known to spread

in crowded settings

Cont…

• CA-MRSA is resistant to

penicillin and methicillin.

• Lead to redness, swelling

and pain resembling to

spider bite.

• Minor skin problems

pimples, insect bites, cuts,

and scrapes especially in

children may lead to MRSA

colonization.

Hospital-acquired MRSA (HA-MRSA)

HA-MRSA Healthcare-acquired Methicillin resistant Staph. aureus

Many hospitals now seeing CA-MRSA in healthcare associated infections

Vancomycin resistance……..?

• Isolate of S. aureus in 1997 was observed

resistant mediated not via acquisition of van A by

a strain of methicillin-resistant S. aureus (MRSA)

but by an unusually thickened cell wall containing

dipeptides capable of binding vancomycin,

thereby reducing availability of the drug for

intracellular target molecules.

• This was the first observation of vancomycin-

intermediate S. aureus (VISA).

Cont….

• The predicted mechanism of van A gene

plasmid-mediated transfer from enterococci

to S. aureus was later observed for the first

time in 2002; this was the first description of

vancomycin-resistant S. aureus (VRSA).

Drugs against MRSA

• Daptomycin

• Linezolid(belonging to oxazolidiones class)

Drugs In Development

• Oritavancin-Binds to normal cell wall

precursors

• Tigecyclin-Works on efflux pumps

• Dalbavancin- Bacteriacidal

Who is at risk for MRSA?

ANYONE can get MRSA – those most at risk:

Spend a lot of time in crowded places such

as hospitals, schools or dorms

Share sports equipment

Share personal hygiene items

Play contact sports

Overuse or misuse antibiotics

Can Healthy People Get MRSA?

• Yes. MRSA skin infections are showing up more

frequently in healthy people, with none of the

usual risks factors.

• This type of MRSA - called community-

associated MRSA (CA MRSA) - has been

reported among athletes, prisoners, and military

recruits.

Diagnosis

• S. aureus infections in humans are diagnosed

by culture and identification of the organism,

as in animals. (Staphylococcal food poisoning

is diagnosed by examination of the food for the

organisms and/or toxins.).

Cont…..

• Methicillin-Resistant Staphylococcus aureus

(MRSA) as the causal agent of nosocomial

infection demands a quick and trustworthy

characterization of isolates

Phenotypic Methods

• Antibiogram typing

• Phage typing

• Serotyping

• Biotyping

• Protein electrophoretic typing

Whole cell protein typing

Immunoblotting

Zymotyping

Genotypic Methods

• Plasmid DNA analysis

• Chromosomal DNA analysis

• Southern blot analysis of RFLP

• Ribotyping

• Binary typing

• Pulsed field gel electrophoresis

Prevention

The best defense against spreading MRSA is to

practice good hygiene, as follows:

• Keep your hands clean

• Use hand sanitizer containing at least 62

percent alcohol.

• Keep cuts and scrapes clean and covered with

a bandage until healed.

• Follow your healthcare provider’s instructions

on proper care of the wound.

• Bandages or tape can be discarded with regular

trash.

Cont…

• Avoid contact with other people’s wounds

or bandages.

• Avoid sharing personal items, such as

towels, washcloths, razors, clothes, or

uniforms.

• Wash sheets, towels, and clothes that

become soiled with water and laundry

detergent; use bleach and hot water if

possible.

Cont….

• Drying clothes in a hot dryer, rather than air-

drying, also helps kill bacteria in clothes.

• Tell any healthcare providers who treat you if

you have or had an S. aureus or MRSA skin

infection.

• If you have a skin infection that requires

treatment, ask your healthcare provider if you

should be tested for MRSA.

Cont….

• Many healthcare providers prescribe drugs that

are not effective against antibiotic-resistant

staph, which delays treatment and creates more

resistant germs.

• Healthcare providers are fighting back against

MRSA infection by tracking bacterial

outbreaks and by investing in products

Vaccination

• Development of StaphVAX®, apolysaccharide conjugate vaccine against S.aureus infections in process.

• The results of the phase 3 clinical trials of thevaccine (Staph VAX) will be presented 2006.

Future Prospects

• What of the future? Many new avenues are

under exploration.

• Tea-tree oil in a nasal application together with

a body wash was shown to be as effective as

mupirocin with antiseptic washes in the

eradication of carriage of MRSA

• Antiseptic-coated endotracheal tubes are

undergoing trials.

Cont…

• Other techniques under investigation include a hydrogen-peroxide-based gas to decontaminate the environment, air filtration units and diagnostic kits, phage therapy and, perhaps the most interesting

• A search of Medline yielded no published data on this last approach. Whatever new answers emerge, we must hope they will not go the way of methicillin.

MRSA- Indian Scenario

• MRSA is endemic in India and is a dangerous

pathogen for hospital acquired infections.

• This study was conducted in Indian tertiary

care centres during a two year period from

January 2008 to December 2009 to determine

the prevalence of MRSA and susceptibility

pattern of S. aureus isolates in India.

Cont….

• In India first MRSA, 6th in world was isolated

in 2005 at Kolkata from the cases of wounds in

children.

• Till than it has been reported from various part

of country including animals and supposed to

be major cause of mastitis in bovines (Kiran,

2014).

• National Guidelines for controlling MRSA

were published in 1998 and are currently under

revision.

• A two-tier control programme was

recommended.

References1. http://www.niaid.nih.gov/topics/antimicrobialresistance/examples/mrsa/pages/default.aspx

2. Mitchell, David.MRSA.”what’s New”. Inoculum. Volume 8, number 2 (1999) 1-12.3. textbookofbacteriology.net/resantimicrobial.htm4. healthsciences.columbia.edu/ dept/ps/2007/mid/2006/transcript_02_mid22.pdf5. http://www.bioteach.ubc.ca/Biodiversity/AttackOfTheSuperbugs6. Foster, Timothy. The staphylococcus aureus “superbug”.J. clin Ivestigation7. Volume number114 (2004) 1693-1696.8. www.channing.harvard.edu/4a.htm9. ww.ncbi.nlm.nih.gov.10. www.aafp.org/afp/ 20000815/804.html11. Journal of Clinical Microbiology, June 2000, p. 2378-2380, Vol. 38, No. 6

0095-1137/04.00+012. www.FDA.com (FDA archives)13. www.postgradmed.com/issues/2001/10_01/hoel.htm14. www.cdc.gov/ncidod/hip/aresist/mrsa_CDCactions.htm15. www.medscape.com16. http://www.nabi.com/images/factsheets/fsStaphVAX.pdf17. http://textbookofbacteriology.net/staph_2.html18. http://aic-server4.aic.cuhk.edu.hk/web8/0205_MRSA.jpg

Cont…

19. Duckworth G. Controlling methicillin-resistant Staphylococcus aureus. BMJ 2003;327: 1177–8[PMC free article] [PubMed]

20. Voss A. Preventing the spread of MRSA. BMJ 2004;329: 521. [PMC free article] [PubMed]21. Thompson DS. Methicillin-resistant Staphylococcus aureus in a general intensive care unit. J R Soc Med2004;97:

521–6 [PMC free article] [PubMed]22. Rolinson GL, Stevens S, Batchelor FR, Cameron Wood J, Chain EB. Bacteriological studies on a new

penicillin. Lancet 1960;ii: 564–9 [PubMed]23. Elek SD, Fleming PC. A new technique for the control of hospital cross infection. Lancet 1960;ii: 569–

72[PubMed]24. Jevons MP. ‘Celbenin-resistant’ staphylococci. BMJ 1961;i: 124–525. Cox RA, Conquest C, Mallaghan C, Marples RR. A major outbreak of methicillin-resistant staphylococci caused by

a new phage type (EMRSA-16). J Hosp Infect 1995;29: 87–106 [PubMed]26. Farrington M, Redpath C, Trundle C, Coomber S, Brown NM. Winning the battle, but losing the war: methicillin-

resistant Staphylococcus aureus (MRSA) at a teaching hospital. Q J Med 1998;91: 539–48[PubMed]27. British Society for Antimicrobial Chemotherapy, Hospital Infection Society, Infection Control Nurses Association.

Revised guidelines for the control of methicillin-resistant Staphylococcus aureus infection in hospitals. J Hosp Infect 1998;39: 253–90 [PubMed]

28. Emmerson AM, Enstone JE, Griffin M, Kelsey MC, Smyth ETM. The Second National Prevalence Survey of Infection in Hospitals—overview of the results. J Hosp Infect 1996;32: 175–90 [PubMed]

29. Barrett SP, Mummery RV, Chattopadhyay. Trying to control MRSA causes more problems than it solves. J Hosp Infect 1998;39: 85–93 [PubMed]

30. Farrington M, Redpath C, Trundle C, Brown NM. Controlling MRSA. J Hosp Infect 1999;40: 251–4[PubMed]•

Cont…

31. Cooper BS, Stone SP, Kibbler CC, et al. Isolation measures in the hospital management of methicillin-resistant Staphylococcus aureus (MRSA): systematic review of the literature. BMJ 2004;329: 533–9[PMC free article] [PubMed]

32. Wertheim HFK, Vos MC, Boelens HAM, et al. Low prevalence of methicillin-resistant Staphylococcus aureus (MRSA) at hospital admission in the Netherlands: the value of the search and destroy and restrictive antibiotic use. J Hosp Infect 2004;56: 321–5 [PubMed]

33. Marshall C, Wolfe R, Kossman T, Wesselingh S, Harrington G, Spelman D. Risk factors for acquisition of methicillin-resistant Staphylococcus aureus by trauma patients in the intensive care unit. J Hosp Infect2004;57: 245–52 [PubMed]

34. Silvestri L, van Saene HKF, Milanese M, et al. Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial. Eur Respir J 2004;23: 921–6 [PubMed]

35. de la Cal MA, Cerda E, van Saene HKF, et al. Effectiveness and safety of enteral vancomycin to control endemicity of methicillin-resistant Staphylococcus aureus in a medical/surgical intensive care unit. J Hosp Infect 2004;56: 175–83 [PubMed]

36. Van Saene HKF, Weir WI, de la Cal MA, Silvestri L, Petros AJ, Barrett SP. MRSA—time for a more pragmatic approach. J Hosp Infect 1998;56: 175–83

37. Howe R, Monk A, Wootton M, Wash T, Enright MC. Vancomycin susceptibility within methicillin-resistant Staphylococcus aureus lineages. Emerg Infect Dis 2004;10: 855–7 [PMC free article] [PubMed]

38. Dryden MS, Dailly S, Crouch M. A randomised, controlled trial of tea tree topical preparations versus a standard topical regime for the clearance of MRSA colonisation. J Hosp Infect 2004;56: 283–6 [PubMed]

39. Pancheco-Fowler V, Gaonakar T, Wyer PC, Modak K. Antiseptic impregnated endotracheal tubes for the prevention of bacterial colonisation. J Hosp Infect 2004;57: 170–4 [PubMed]

40. French GL, Otter J, Shannon KP, Adams NMT, Watling D, Parks MJ. Tackling hospital environmental contamination with methicillin-resistant Staphylococcus aureus (MRSA): a comparison between conventional terminal cleaning and hydrogen peroxide vapour decontamination. J Hosp Infect (in press)[PubMed]