Methicillin resistant Staphylococcus aureus (MRSA ) in humans and animals

1. Methicillin resistant Staphylococcus aureus (MRSA) in humans and animals Update march 2008

2. 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.

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

4. 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

5. 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 to multiple classes of antibiotics

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

12. MRSA in human:mechanisms of resistance • 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) • 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

13. MRSA: epidemiology

14. 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)

15. MRSA in human: prevalence in US: SA=32% and MRSA=0.84%; 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 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

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

20. MRSA in animals

21. 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 To read the full article

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, muzzles….0%

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)

31. 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

33. 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 foundin 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

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. To read the full article

43. MRSA in vets In: Clin Microbiol Infect. 2008;14 (1):29-34. To read the full article

44. 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

45. 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