Thursday, 13 February 2014

METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS(MRSA) - A PUBLIC HEALTH CONCERN FOR CANADA


Staphylococcus aureus has been around since thousands of year as natural commensal of human body.But, Methicillin Resistant Staphylococcus aureus has been found since early 1960's.The term"Methicillin Resistant" means that the bacteria are not affected by methicillin as well as all other B-lactum antibiotcs. There are around 16 strains of different MRSA, with varying degrees of resistance to methicillin.1,2
MORPHOLOGY: It is gram positive,non fastidious cocci, also known as "cluster of grapes". It produces enzymes such as catalase, coagulase and hemolysin.3
 4
SYMPTOMS: It is an opportunistic pathogen that can cause myriad of diseases that is why also known as "SUPERBUG". The 1-10 days period between MRSA transmission and the beginning of symptoms is called "MRSA incubation period.5
1. Skin Infection:  Impetigo, Cellulitis, Scalded skin syndrome, Mastitis.
2. Blood Infections:Boils, Carbuncle, Styes, Endocarditis, Abscess, Osteomyleitis, Septic Shock,Septicemia, Sinusitis and Meningitis.           
3. Gastrointestinal Infection: Nausea, Vomiting, Diarrhea, Dehydration.
4. Toxic Shock Syndrome:Sudden onset of fever, Low Blood Pressure, Shock, Death.6                                                 
                                Sites infected and symptoms produced by S.aureus13
PATHOGENESIS:     1. Direct Contact.
                                   2. Indirect contact
                                   3. Airborne infection

Types of Infection:

      Characteristic
            HA-MRSA
           CA-MRSA
       Clinical
  Surgical Site infections,       invasive
Skin infections, rarely invasive, multiple, recurrent
      Epidemiology 
    Old, Healthcare
Young, Athletes, Drug   users, Military
   Antibiotic resistance
  Multidrug resistant
B-Lactum resistance
   Chromosomal element      carrying methicillin            resistant gene                    (SCCmec)
            IV,V
     I,II,III
    Panton-Valentine                leukocidin toxin 
            Rare          
     Frequent


HISTORY: Initially, pencillin resulted in decreased death rates from S.aureus, but very soon penicillin resistant S.aureus 80/81 resistant strain was found. Then, methicillin was introduced in 1950's to treat pencillin resistant S.aureus but in 1961's there were reports of emerged cases of methicillin resistant S.aureus. Further, vancomycin was approved by Food and Drug Administration but in 1987 resistance to it was seen and In June 2012, S.Aureus strain that was fully resistant to vancomycin was isolated.7

Knowledge about evolution of S.aureus into resistant strains:
Mutations occurs at rate of one base pair every six weeks that lead to accumulation of mutated genes.10mecA gene situated on staphylococcal cassette chromosome mec (SECCmec) is responsible for providing resistance via horizontal transmission9. Evolution mechanism involves two ways:
1. Evolution via vertical transmission: Mutation that ups the individual's ability to survive and reproduce.
2. Evolution via horizontal transmission: Mechanism that if distantly related species develop a mutation for the benefit, the other species can incorporate that mutated gene via plasmid into their own DNA and can develop that mutation.                                                                                                                                   9

MRSA THREAT FOR PUBLIC HEALTH IN CANADA:

MRSA is endemic worldwide. The percentage of MRSA among S.aureus isolates in US hospitals increased from 2.4% to 53% in 2003.Though, in Canada the rates are less in comparison to US, but outbreaks are noticed that resulted in increased prevalence from 0.50 to 9.47 per 1000 admissions between 1995 to 2009.11 However, European Countries have the least outbreaks of MRSA per annum in comparison to other.2


Frequency of detection of MRSA Rates in the CNISP network from 1995 to 2009

Surveillance Years
MRSA Infections
   MRSA Colonizatios
Numerator
Denominator
Denominator
    Patient    Admissions
    Patient
     Days
    1995
        106
              83
        189
     374,027
 2,907,905
    1996
        192
             247
        440
     405,791
 3,801,608
    1997
        293
             358
        653
     418,465
 3,625,997
    1998
        418
             616
       1050
     407,297
 2,990,598
    1999
        513
            1381
       1953
     510,095
 4,078,163
    2000
        736
            1781
       2553
     507,910
 3,862,873
    2001
        696
            1602
       2328
     614,421
 4,967,214
    2002
        845
            1849
       2729
     583,658
 4,732,172
    2003
       1064
            2390
       3465
     671,240
 5,611,833
    2004
       1369
            2642
       4019
     677,829
 5,227,447
    2005
       2067
            3427
       5636
     764,341
 6,493,286
    2006
       2011
            3850
       5867
     770,118
 5,963,506
    2007
       1952
            4335
       6287
     768,294
 5,695,520
    2008
       2001
            4364
       6273
     678,610
 5,441,458
    2009
       2036
            4610
       6646
     701,477
 5,374,036

(CNISP: Canadian Noscomial Infection Surveillance Program
MRSA: Methicillin Resistant Staphylococcus Aureus
PATIENT ADMISSIONS: Number Of Patients Admitted /Hospitalized During A Surveillance Year (One Patient Can Have Multiple Hospitalizations)
PATIENT DAYS: Total Number Of Days That Each Patient Spent Hospitalized During A Surveillance Year.)12
From 1995-2009, continued increase in MRSA rates in Canada has accounted for rise in annual costs of MRSA treatment from $10.6 million to approximately $120 million averaging to $12.216 per patient.11

 Overall MRSA rates, CNISP 1995-2009 per 1,000 patient admissions 12
                       
                   
Annual cost on overall MRSA rates from 1995-2010 11


Average annual medical expenditure  per MRSA patient 11


           
  Differences in MRSA Rates with Geographical Distribution:
MRSA has been the emerging cause of morbidity among people in Canada especially CA-MRSA.11 Since last six years, Central Canada continues to post the highest rate in comparison to East and West.10 CA-MRSA was reported to be endemic in first nations and Métis communities in northern Saskatchewan accounting for 62% of MRSA-positive.In Manitoba 40% positive MRSA cases were CA-MRSA. Crowding, lack of good quality running water and heavy antibiotic use are supposed to be associated risk factors. Outbreaks of CA-MRSA have also been reported in southern Ontario, British Columbia and Alberta. Important differences observed in MRSA rates in different parts of country are considered due to variations in antimicrobial use and infection control practices.11

Regional distribution of MRSA Rates in CNISP network from 1995 to 2009

 SURVEILLANCE  YEARS
              MRSA Infections
     MRSA Colonisations
EAST
CENTRE
WEST
EAST
CENTRE
WEST
            1995
   5
56
45
4
55
24
            1996
   4
137
51
23
191
33
            1997
16
711
106
66
293
49
            1998
12
226
180
20
437
159
            1999
11
371
31
29
998
354
            2000
21
410
305
51
336
394
            2001
28
416
252
50
1243
309
            2002
53
514
278
109
1408
332
            2003
99
592
373
251
1818
321
            2004
106
594
669
249
1970
423
            2005
193
687
1187
308
2364
755
            2006
189
751
1071
303
2662
885
            2007
207
618
1127
312
2816
1207
            2008
261
659
1081
452
2933
979
            2009
217
858
961
312
3176
1122

(East: New Brunswick,Newfoundland,Nova Scotia
Centre: Quebec and Onatrio
West:    Manitoba,Saskatchewan,Alberta and British Columbia )12
Regional MRSA Rates,CNISP 1995 to 2009 (per 1,000 patient admissions)12

             

Differences in admission rates according to age and type of infection:                       
Elderly people with weakened immune systems, chronic conditions or who have undergone recent surgical procedure are more susceptible to hospital acquired infection.6 However, almost a third of all new MRSA cases appear to be paediatric community associated12.Even,South Texas has also noticed 14-fold increase between 1999 and 2001 among children. Reason suggested behind this is that CA-MRSA strains display enhanced virulence and illness, spread more rapidly than traditional HA-MRSA infections.13
Health care associated MRSA infection by hospital type, CNISP 2008-2009 (per 1000 patient-admissions)12

  Community care associated MRSA infection by hospital type,CNISP 2008-2009(per 1000 patient-admissions)12


HOW TO DIAGNOSE MRSA??
1. Bacterial Culture: A screening culture identifies the MRSA.
2. Molecular test: The specimen here is analyzed for the genetic markers to identify the mec A gene that confers resistance.14
3. Synthetic Probe: New technique that detects pathogen by its nuclease enzyme.15
WHY MRSA EMERGED AS BIG THREAT SINCE PAST FEW YEARS??   
 1. Widespread use of antibiotics in this modern era of medical science.9
 2. General Selection of antibiotics: Selecting general antibiotic allows weaker bacteria to die but strong ones will pass their genetic adaptations to their offspring's.
 3. Dislike of antibiotics by human beings: Not completing antibiotic course. 16,17     

17

SUGGESTED GUIDELINES FOR PREVENTION AND TRANSMISSION: 
No simple solution exists to prevent escalation of MRSA rates, but certain guidelines have been enlisted to prevent further development of resistance and transmission of bacteria.
1. Reduce the usage of antibiotics.                                                                                               
2. Encourage patients to finish the whole course of prescribed antibiotics.8, 12                          
3. Personal and care giver hygiene measures.
4. Canadian government guidelines do not permit use of decolonization agents as they promote resistance development.11  
5. Compliance with barrier precautions along with educational measures..  

CURRENT STRATEGIES UNDER ACTION BY PUBLIC HEALTH AGENCY OF CANADA:        
1. Public Health Agency of Canada (PHAC) is supporting CNISP to continue the program of surveillance of MRSA cases.                                                                                                    
2. PHAC, has partnered with the Community Healthcare Infection Control Association of Canada and the Canadian Patient Safety Institute to co-lead a new antibiotic resistant organism reduction teaching module for Safer Healthcare Now (SHN).That includes training front line health care workers.
3. PHAC is also finding ways to start and support a multi-partner approach to reduce the incidence and prevalence of MRSA.18 

TREATMENT:
1. Till date no perfect treatment has been discovered but use of new generation antimicrobial such as glycylcyline has been found effective.
2. Cephalosporin ceftobiprole has also been used in management of MRSA patients.
3. It has been suggested by William Fencial, that a compound from Streptomyces may become an effective treatment against MRSA as it contain anthracimycin, a new and unique chemical that has great potential to develop into a new antibiotic medication.16

Summarizing, it can be said that a genuine infection with MRSA is not a joke and as prevalence of MRSA is increasing gradually but continually in Canada10. So, a collaborative approach is needed to identify MRSA cases and to get a more structured and regulated public health response.
References:
1.Staphylococcus aureus [Internet][Updated 2014,Feb 2;CIted 2014 Feb 7]Available from:http://www.punchng.com/health/sunday-doctor/staphylococcus-infections/

2.Research on methicillin resistant staphylococcus aureus nursing essay[Internet]2003 [Cited:2014 Feb 2]Available from: http://www.ukessays.com/essays/nursing/research-on-methicillin-resistant-staphylococcus-aureus-nursing-essay.php#ixzz2sCtMjjci  

3.Characterstics of Staph aureus Infections[Internet][Updated 2011,May 3;Cited 2014 Feb 7]Available from: http://www.livestrong.com/article/83622-characteristics-staphylococcus-aureus/

4.Images of Staphylococcus Aureus[Internet][Cited 2014 Feb 6]Available from:http://www.bing.com/images/search?q=methicillin-resistant+staphylococcus+aureus&FORM=HDRSC2

5.Health promotion brought to life.Incubation period of MRSA[Internet][Cited 2014 Feb 7]Available from:http://bacteria.emedtv.com/mrsa/incubation-period-for-mrsa.html

6.Medicine Net.Com;We Bring Doctor’s Knowledge to You;Staph aureus [Internet][Cited 2014 Feb 7]Available from:[http://www.medicinenet.com/staph_infection/page2.htm


7.Matouskova I.,Janout V.;Current Knowledge of Methicillin Resisant  Staphylococcus Aureus and Community Associated Methicillin Resistance Staphylococcus Aureus[Accepted 2008,August 5;Cited 2014 Feb.6] Available From: http://biomed.papers.upol.cz/artkey/bio-200802-0002_CURRENT_KNOWLEDGE_OF_METHICILLIN-RESISTANT_STAPHYLOCOCCUS_AUREUS_AND_COMMUNITY-ASSOCIATED_METHICILLIN-RESISTANT.php#.UvvvkcaHsWY

8.Canadian Journal of Infectious Diseases and Medical Microbiology[Internet][Updated 2007,Jan;Cited 2014 Feb 8]Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542887/table/t1-jidmm18027/

9.Understanding Evolution,Superbug,superfast evolution[Internet] [Updated 2008 ;Cited 2014 Feb 7]Available from: http://evolution.berkeley.edu/evolibrary/news/080401_mrsa

10.Sequencing Staph:New Genetic Analysis Tracks MRSA Mutations[Internet][Updated 2010,21;Cited 2014 Feb 7]Available from:http://www.scientificamerican.com/article/mrsa-genome-sequencing/

11.Goetghebeur M.,Landary P.A.,Han D.,Vicente C.,Methicillin Resistant Staphyloccous Aureus:A Public Health Issue With Economic Consequence[Internet][Upated 2007,Jan;Cited 2014 Feb 8]Available Form: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542887/

12.Public Health Agency of Canada,Results of Surveillance of Methicillin Resistant Staphylococcus Aureus from 1995-2009.[Internet][Updated 2011,Feb 3;Cited 2014 2014 Feb 6],Availiable from:http://www.phac-aspc.gc.ca/nois-sinp/projects/res2009/index-eng.php?#f3a

13.Todar's online book of Bacteriology,Staphylococcus[Internet][Cited 2014,Feb 6]Availiable from:http://textbookofbacteriology.net/staph_5.html

14.Lab Test Online;MRSA screening[Internet][Updated 2013 August,6;Cited 2014,Feb 8]Availiablefrom:http://labtestsonline.org/understanding/analytes/mrsa/tab/test

15.Reasearhers Develop Probe To Detect Staph Bacteria[Internet][updated 2014 Feb 6;Cited Feb 2014 7]Availiable from:http://vaccinenewsdaily.com/medical_countermeasures/329662-researchers-develop-probe-to-detect-staph-bacteria/

16.What is MRSA?Why is MRSA a concern?How is MRSA treated?[Internet][Updated 2013 July 19:Cited 2014,Feb 8]Availiable from:http://www.medicalnewstoday.com/articles/10634.php

17.Superbug[Internet][Uploaded 2009,Jan 15;Cited 2014,Feb 9]Available from: http://www.youtube.com/watch?v=GBPQL6NcsiM

 18.Public Health Agency Of Canada,Fact Sheet-Methicillin Resistant Staph Aureus[Internet][2008,July 8;Cited 2014Feb 7]Avialiable from:http://www.phac-aspc.gc.ca/id-mi/mrsa-eng.php.
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