MRSA

BIOTECHNOLOGY

1. Methicillin Resistant Staphylococcus aureus : Current Status & Future Scenerio JAYSHREE Ph.D SCHOLAR

2. 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

3. Virulence Determinants of Staphylococcus aureus

4. Frequency of Staphylococcus aureus colonization in carriers on various body sites Nose 100% Skin chest 45% Perineum 60% Ankle 10% Axilla 19% Hand 90% Forearm 45% 4

5. S. aureus – as pathogen virulent factors (toxins and enzymes) Frequent nosocomial - and community-acquired pathogen Mode of transmission – contact Clinical manifestations 1/29/2015 5

6. Superficial Infections

7. Scalded Skin Syndrome: Classic Toxic Shock

8. S ystemic Menstrual Toxic Shock

9. 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

10. Cont… In the 1940s, medical treatment for  S. aureus   infections became routine as Penicillin was introduced as drug of choice. Penicillin- bacterial cell wall synthesis- inflow of water- cell burst

11. 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

12. 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 .

13. 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 .

14. 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

15. 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 ?

16. How “Tough” is MRSA? Staphylococci can survive many extreme environmental conditions. The bacteria can be cultured from dried clinical material after several months, are relatively heat resistant, and can tolerate high salt media. So, “What Do we Do?” You can not get rid of MRSA; you can only control it.

17. 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

18. CA-MRSA and HA-MRSA CA-MRSA Unique microbiologic and genetic properties compared with HA-MRSA may allow the community strains to spread more easily or cause more skin disease

19. 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

20. 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.

21. Hospital-acquired MRSA (HA-MRSA) HA-MRSA Healthcare-acquired Methicillin resistant Staph. aureus Many hospitals now seeing CA-MRSA in healthcare associated infections

22. 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).

23. 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).

24. Drugs against MRSA Daptomycin Linezolid (belonging to oxazolidiones class)

25. Drugs In Development Oritavancin-Binds to normal cell wall precursors Tigecyclin-Works on efflux pumps Dalbavancin- Bacteriacidal

26. 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

27. 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.

28. 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.).

29. Cont….. Methicillin -Resistant Staphylococcus aureus (MRSA) as the causal agent of nosocomial infection demands a quick and trustworthy characterization of isolates

30. Phenotypic Methods Antibiogram typing Phage typing Serotyping Biotyping Protein electrophoretic typing Whole cell protein typing Immunoblotting Zymotyping

31. Genotypic Methods Plasmid DNA analysis Chromosomal DNA analysis Southern blot analysis of RFLP Ribotyping Binary typing Pulsed field gel electrophoresis

32. 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 .

33. 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.

34. 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.

35. 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

36. Vaccination Development of StaphVAX®, a polysaccharide conjugate vaccine against S. aureus infections in process. The results of the phase 3 clinical trials of the vaccine (Staph VAX) will be presented 2006.

37. 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.

38. 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.

39. 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.

40. Cont…. In India first MRSA, 6 th 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).

41. National Guidelines for controlling MRSA were published in 1998 and are currently under revision . A two-tier control programme was recommended.

42. References http://www.niaid.nih.gov/topics/antimicrobialresistance/examples/mrsa/pages/default.aspx Mitchell, David.MRSA.”what’s New”. Inoculum . Volume 8, number 2 (1999) 1-12. textbookofbacteriology.net/resantimicrobial.htm healthsciences.columbia.edu/ dept/ ps /2007/mid/2006/transcript_02_mid 22 .pdf http://www.bioteach.ubc.ca/Biodiversity/AttackOfTheSuperbugs Foster, Timothy. The staphylococcus aureus “ superbug”.J . clin Ivestigation Volume number114 (2004) 1693-1696. www.channing.harvard.edu/4a.htm ww.ncbi.nlm.nih.gov. www.aafp.org/afp/ 20000815/804.html Journal of Clinical Microbiology , June 2000, p. 2378-2380, Vol. 38, No. 6 0095-1137/04.00+0 www.FDA.com (FDA archives) www.postgradmed.com/issues/2001/10_01/hoel.htm www.cdc.gov/ncidod/hip/aresist/mrsa_CDCactions.htm www.medscape.com http://www.nabi.com/images/factsheets/fsStaphVAX.pdf http://textbookofbacteriology.net/staph_2.html http://aic-server4.aic.cuhk.edu.hk/web8/0205_MRSA.jpg

43. Cont… Duckworth G. Controlling methicillin -resistant  Staphylococcus aureus . BMJ 2003;327: 1177–8[ PMC free article ] [ PubMed ] Voss A. Preventing the spread of MRSA. BMJ 2004;329: 521. [ PMC free article ] [ PubMed ] Thompson DS. Methicillin -resistant  Staphylococcus aureus  in a general intensive care unit. J R Soc Med2004;97: 521–6 [ PMC free article ] [ PubMed ] Rolinson GL, Stevens S, Batchelor FR, Cameron Wood J, Chain EB. Bacteriological studies on a new penicillin. Lancet 1960;ii: 564–9 [ PubMed ] Elek SD, Fleming PC. A new technique for the control of hospital cross infection. Lancet 1960;ii: 569–72[ PubMed ] Jevons MP. ‘ Celbenin -resistant’ staphylococci. BMJ 1961;i: 124–5 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 ] 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 ] 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 ] 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 ] Barrett SP, Mummery RV, Chattopadhyay . Trying to control MRSA causes more problems than it solves. J Hosp Infect 1998;39: 85–93 [ PubMed ] Farrington M, Redpath C, Trundle C, Brown NM. Controlling MRSA. J Hosp Infect 1999;40: 251–4[ PubMed ]

44. 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 ] 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 ] 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 ] 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 ] 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 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 ] 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 ]   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 ] 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 ]