Methicillin resistant Staphylococcus aureus (MRSA) in humans and animals

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01/29/22 5-AB Resistance mrsas -1

Methicillin resistant

Staphylococcus aureus (MRSA) in humans and animals

Update march 2008

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Overview of SA & MRSA in human

1. Staphylococcus aureus (SA) is part of normal human bacterial flora, and is found primarily in the nares

2. SA can causes serious invasive infections

including endocarditis, osteomyelitis, bacteriema,

pneumonia and toxic shock syndrome.

(3)

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-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

(6)

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

(7)

S. aureus : nosocomial infections in humans

• Superficial infections

• Wound infections

• Catheter infections

• Endocarditis

• Bacteraemia with sepsis

– Mortality of around 50%

(8)

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

(9)

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

(10)

MRSA: treatment

MRSA are sensitive to vancomycin,

teicoplatin, nitrofurantoin, rifampicin,

linezolid and quinopristin-dalfopristin;

(11)

MRSA: mechanisms of resistance

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MRSA in human:

mechanisms 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: SA=32% and MRSA=0.84%;

2. In Japan: MRSA=67% .

(16)

MRSA: epidemiology

• up until recently, MRSA was primarily associated to hospital acquired

infections but has now been involved

as a community-acquires bug

(17)

Overview of SA & MRSA in human epidemiological 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

(18)

MRSA in animals

• In animal, first reported in 1972 (milk of

mastitic cow)

(19)

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)

(22)

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

(23)

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)

(24)

MRSA in horse

(Ontario Vet College 2002)

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

personnel

(25)

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

(26)

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

• Stalls: MRSA positive horses:62%

• Stalls: MRSA negative horses:6.9%

• Medical equipment :5.6%

• Floors: 0%

• Personal equipment (clinician):4.8%

• twitches:10.5%

• Horse handling equipment, soap dispenser,

(27)

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)

(28)

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

(29)

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)

(30)

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

(32)

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

(34)

MRSA: An Irish survey 2005 (5)

• Pattern of isolates from horses were

unlike any pattern previously reported in

man isolates

(35)

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

(36)

MRSA in food producing

animals

(37)

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

(38)

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.

(39)

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

(40)

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.

(41)

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%)

(42)

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.

(43)

MRSA in vets

In: Clin Microbiol Infect. 2008;14 (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

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MRSA in animal What 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