5-AB Resistance mrsas -1

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Methicillin resistant Staphylococcus aureus
(MRSA) in humans and animals
Update march 2008
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Overview of SA MRSA in human

• Staphylococcus aureus (SA) is part of normal
  human bacterial flora, and is found primarily in
  the nares
• SA can causes serious invasive infections
  including endocarditis, osteomyelitis,
  bacteriema, pneumonia and toxic shock syndrome.

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SA MRSA treatments

• Before penicillin mortality rate from invasive SA
  was 90
• Penicillin has a dramatic effect
• However resistance developed
• Introduction of Methicillin in 1950 to the
  treatment of SA resistant to penicillin

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Methicillin

• Antibiotic methicillin introduced into clinical
  practice in 1959
• Semi synthetic penicillin
• First resistance reported in 1961 in UK
• Pour en savoir plus sur la meticilline

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Methicillin-resistant Staphylococcus aureus
(MRSA)

• The organism is often sub-categorized as
  Community-Associated MRSA (CA-MRSA) or
  Hospital-Associated MRSA (HA-MRSA) depending upon
  the circumstances of acquiring disease, based on
  current data that these are distinct strains of
  the bacterial species

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MRSA as a leading cause of nosocomial infections
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MRSA in human nosocomial infections

• Major cause of morbidity and mortality in human
  Intensive Care Units (ICU)
• Up to 50 staphylococcal infections in human ICUs
  are now due to MRSA
• Transmission via transiently colonised hands of
  health care workers
• Hospital acquired strains commonly resistant to
  multiple classes of antibiotics

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S. aureus nosocomial infections in humans

• Superficial infections
• Wound infections
• Catheter infections
• Endocarditis
• Bacteraemia with sepsis
• Mortality of around 50

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MRSA transmission

• Hand-to hand transmission
• From infected patients
• From environment
• Floor
• (27 of surface in room of MRSA positive
  patient)
• Door handles
• Computer
• etc

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MRSA has become a major nosocomial pathogen in
human hospital

• Cause concern by
• because of the extent of antimicrobial resistance
  (to many antibiotics)
• Potential for transmission among patients and
  hospital personnel

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MRSA treatment

• MRSA are sensitive to vancomycin, teicoplatin,
  nitrofurantoin, rifampicin, linezolid and
  quinopristin-dalfopristin

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MRSA mechanisms of resistance
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MRSA in humanmechanisms of resistance

1. Methicillin resistance in SA is encoded by the
   mecA gene, which is located on a mobile genetic
   element called the Staphylococcal Cassette
   Chromosome mec (SCCmec)
2. This gene encode a penicillin binding protein
   (PBP2) that has a low affinity for beta lactams
   and confers resistance to all beta lactam
   antibiotic including cephalosporins

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MRSA epidemiology
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MRSA epidemiology

• In human, fist reported in UK in 1961 and now a
  world-wide problem
• In animal, first reported in 1972 (milk of
  mastitic cow)

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MRSA in human prevalence

1. in US SA32 and MRSA0.84
2. In Japan MRSA67 .

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MRSA epidemiology

• up until recently, MRSA was primarily associated
  to hospital acquired infections but has now been
  involved as a community-acquires bug

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Overview of SA MRSA in humanepidemiological
facts (US 2005)

• The standardized incidence rate of invasive MRSA
  was 31.8 per 100 000 persons year
• The standardized mortality rate was 6.3 per 100
  000 and extrapolation to a national level
  predicted about 19000 deaths annually associated
  to MRSA i.e more deaths than attributed to AIDS
  in that year!
• A meta-analysis studies found that the risk of
  mortality due to invasive MRSA infections was
  approximately twofold that seen with invasive
  methicillin sensitive SA

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MRSA in animals
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SA in animals

• A ubiquitous commensal with a host range that
  span to all vertebrates
• In domestic animals, SA is primarily an
  opportunistic pathogen associated with sporadic
  infections,
• but it is a major etiological agent of bovine
  mastitis
• An Update on Staphylococcus aureus Mastitis

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MRSA in animals

• In animal, first reported in 1972 (milk of
  mastitic cow)

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MRSA in animals
Davies P Methicillin resistant Staphylococcus
aureus people, pigs and pets In Am Assoc Swine
Vet 2008 P15-20
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MRSA in animals
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MRSA transmission between animals to man

• Until recently, it was accepted that epidemiology
  of transmission and antimicrobial resistance of
  MRSA were essentially confined to the human
  arena, and that animals reservoir were of
  negligible importance
• Animal can act as reservoir of MRSA ( cat, dogs,
  horse, chicken, rabbit, pig, guinea pigs, turtle,
  parrot, etc.)
• Currently we have evidences of MRSA
  animal-to-human transmission (e.g from horse to
  human)

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MRSA in animals

• SA is a highly versatile organism that
  demonstrates a considerable degree of adaptation
  among host species explaining that interspecies
  transmission is a common event

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MRSA in animals

• 11 dogs from USA/UK with clinical MRSA infection
  reported in 1999
• Increasing isolation rate by UK veterinary
  clinical microbiology laboratories
• Recent reports of an outbreak in a Canadian
  equine hospital
• Horse and humans had same MRSA
• 9.6 environmental sites cultured positive
• 4.7 of horses are colonised

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MRSA transmission between animals to man

• recently, 2 outbreaks of infections in separate
  vet teaching hospitals in US and Canada
• In US, the hospital staff were the primary source
  of infection
• In Canada, environmental contamination (stalls
  housing MRSA-positive horses)

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MRSA in horse (Ontario Vet College 2002)

• Asymptomatic nasal carriage of MRSA in 26
  hospitalized horses and 16 vet personnel

To read the full article
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MRSA at Ontario

• Canadian epidemic MRSA 5 (CMRSA-5)
• Indistinguishable from an uncommon human isolate,
  and it is suspected that this strain originated
  in people but has adapted for survival in horses
• Now being propagated in the equine population
• High prevalence of colonization on some horse
  farm
• Horse can transmit MRSA to vet personnel

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Isolation of MRSA from environment in a vet
teaching hospital (Weese 2002)

• Stalls MRSA positive horses62
• Stalls MRSA negative horses6.9
• Medical equipment 5.6
• Floors 0
• Personal equipment (clinician)4.8
• twitches10.5
• Horse handling equipment, soap dispenser,
  muzzles.0

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MRSA

• Colonisation is transient and elimination within
  few weeks if no re-infection from other horses
• Treatment
• Avoid to use vancomycin and related antibiotics
  in horse (ethical reasons)
• Other treatments to be validated (e.g.
  antimicrobial nebulization)

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MRSA An Irish survey 2005 (1)Objectives

• To report the isolation of MRSA from animals and
  their corresponding personnel attendants
• To investigate relationship between the isolates
  from animals and the vet staff
• To investigate relationship between the isolates
  from animals and general human population to
  elucidate whether human-to-animal or
  animal-to-human transmission might have occurred

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MRSA An Irish survey 2005 (2)sampling

• Recovery of MRSA in animals with respiratory,
  urinary tract or wound infection and animal
  subjected to surgery following treatment in 1 vet
  hospital and 16 private vet clinics
• MRSA was recovered from 25 animals ( 14 dogs, 8
  horses, 1 cat, 1 rabbit 1 seal) and also 10
  attendant vet personnel (healthy carriers)

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MRSA An Irish survey 2005 (2)Epidemiological
typing

• Epidemiological typing by antibiogram-resistogram
  (AR) typing, biotyping and by chromosomal DNA
  restriction fragment length polymorphism analysis
  using SmaI digestion followed by pulsed field gel
  electrophoresis (the gold standard for DNA
  fingerprint of MRSA)

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MRSA An Irish survey 2005 (3)Results

• Clinical susceptibility testing suggested that
  the 35 isolates from animals fell into 2 groups
• Group1 (non-equine isolates) ressistant to 1
  or more of the following AB (macrolides,
  lincosamines, tetra and/or fluoroquinolones
• Group2 (equine isolates) resistant to
  macrolides, aminoglycosides, tetra, TMP/sulfa and
  variably rsistant to fluoroquinolones,
  lincosamines and rifampicin

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MRSA An Irish survey 2005 (4)Epidemiological
typing confirmed the 2 major clusters

• Most non-equine isolates were indistinguishable
  from each other and from the isolates from
  personnel caring for these animals
• MRSA isolated from horses and from their
  attendant personnel were indistinguishable and
  were unlikely the pattern obtained from other
  animal isolates

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MRSA An Irish survey 2005 (5) Comparison of
isolates from vet sources with patterns from MRSA
recovered in human hospital

• It was shown that the most frequently occuring
  pattern of MRSA from non-equine animals was
  indistinguishable from the predominant pattern
  obtained from the most prevalent MRSA strain in
  the human population

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MRSA An Irish survey 2005 (5)

• Pattern of isolates from horses were unlike any
  pattern previously reported in man isolates

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MRSA An Irish survey 2005 (6)

• 2 strains of MRSA is occurring in vet practice
  and one of the strain (non-equine) may have
  arisen from human hospital
• The souce of the second strain (equine) remains
  to be determined

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MRSA in food producing animals
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MRSA in animals the 3 key questions

1. What is the relative importance of animal
   reservoirs and animal-to-human transmission of
   MRSA (particularly in relationship to the
   increase in community acquired disease)
2. What is the role of antibiotic use in food
   animals and companion animals in the epidemiology
   of MRSA in animal reservoir
3. What is the risk of farm-to-table foodborne
   transmission of MRSA via meat?

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MRSA in swine

• Several species of staphylococci, including SA, S
  hyicus and S epiermidis can be routinely isolated
  from domestic pigs and can be considered part of
  the normal flora of swine
• No specific disease associated to SA in pigs

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• A French studies has documented antimicrobial
  resistance of commensals in pigs and pig farmers,

In that study, 5 MRSA isolates were found in
pigs, including one strain (ST 398 on multilocus
sequence typing) that has since been associated
with pigs in other countries. A small number of
pig associated strains were found in farmers
across a wide geographic range in France, leading
the authors to conclude that pig farming could be
a risk factor of staphylococcal infection of
farmers. To read the full article
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MRSA in swine

• A national Dutch survey of 540 pigs slaughtered
  in nine slaughterhouses, found 39 of the pigs
  (and 44 out of 54 groups of pigs) to be positive
  for MRSA in their nares.
• 39 All the isolates belonged to a single clonal
  group, MLST 398,
• Dutch studies estimate the prevalence of the
  ST398 clone in people with occupational exposure
  to pigs to be 760 times higher than that of the
  general population.
• investigations in other European countries
  (Belgium, Germany, Denmark) indicate that the
  occurrence of MRSA in swine is not a problem
  limited to the Netherlands

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MRSA foodborne route of transmission

• S aureus can frequently be isolated from pig
  carcasses, though generally resistant isolates
  have not been predominant
• However concerns about foodborne risk have been
  reinforced by the first report of a life
  threatening infection with the pig ST 398
  MRSA-strain in a 63-year-old Dutch woman who was
  not exposed to pigs, suggesting indirect
  (possibly foodborne) routes of transmission.

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MRSA in pigs

• The role of antibiotic use remains uncertain
• isolates have been almost uniformly resistant to
  tetracyclines,
• a study of 65 pig associated MRSA in Holland
  found all isolates were sensitive to vancomycin,
  teicoplanin, nitrofurantoin, rifampicin,
  linezolid, and quinupristin-dalfopristin, with
  variable sensitivity to erythromycin (40),
  clindamycin (48), cotrimoxazole (48),
  aminoglycosides (92), and quinolones (94)

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MRSA colonization is an occupational risk for
veterinary professionals
MRSA was isolated from nares of 27/417 (6.5)
attendees at an international veterinary
conference 23/345 (7.0) veterinarians, 4/34
(12.0) technicians, and 0/38 others.
To read the full article
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MRSA in vets
In Clin Microbiol Infect. 200814 (1)29-34.
To read the full article
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MRSA in vets (Wulf et al 2008)

• A convenience sample of 272 participants at an
  international conference on pig health in Denmark
  was screened for MRSA carriage using combined
  nose / throat swabs and were asked to complete a
  questionnaire concerning animal contacts,
  exposure to known MRSA risk-factors, and the
  protective measures taken when entering pig
  farms.
• In total, 34 (12.5) participants from nine
  countries carried MRSA.
• Thirty-one of these isolates were non-typeable
  by pulsed-field gel electrophoresis
• All of the non-typeable isolates belonged to spa
  types (t011, t034, t108, t571, t567 and t899)
  that correspond to multilocus sequence type 398.
• Protective measures, e.g., masks, gowns and
  gloves, did not protect against MRSA acquisition.
• Transmission of MRSA from pigs to staff tending
  to these animals appears to be an international
  problem, creating a new reservoir for
  community-acquired MRSA (CA-MRSA) in humans in
  Europe, and possibly worldwide.
• .

To read the full article
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MRSA in animalWhat to do?

• If MRSA become endemic, the problem is extremely
  difficult to control
• Aggressive infection control measures can be
  successful if applied when MRSA is first
  recognized in an institution
• Guidelines for the control of MRSA in animals
  need to be formulated as a matter of urgency to
  minimise futur problems