Epidemiology of MRSA in Australia Graeme R Nimmo Director, Division of Microbiology Pathology Queensland Central Laboratory, Herston QLD 429 Tel: (7) 3636 8 Fax: (7) 3636 1336 Email: Graeme_Nimmo@health. qld.gov.au Geoffrey W Coombs Chief Scientist, Dept Microbiology and Infectious Diseases PathWest Laboratory Medicine WA Royal Perth Hospital, Perth WA 6 Methicillin-resistant Staphylococcus aureus (MRSA) has presented challenges to laboratories and clinicians since it first appeared in Australia in the mid-196s. However, in spite of its long presence and familiarity, a clear understanding of its epidemiology has only been possible with the recent advent of sequence-based typing methods (see the article by O Brien and Giffard, page 131). Archaic MRSA Staphylococcus aureus resistant to methicillin were reported soon after its introduction in 196. The initial reports were from the United Kingdom 1 and it was not until 1968 that MRSA was reported in Australia by Rountree and Beard 2. These archaic MRSA were limited to relatively few institutions, were not associated with widespread epidemics and appear to have been less virulent than later healthcare-associated MRSA 3. They were generally streptomycin-, tetracycline- and erythromycin-resistant but were susceptible to gentamicin. Using multi-locus sequence typing (MLST) and SCCmec typing, archaic MRSA have been characterised as ST-MRSA-I 4. Epidemic multi-resistant MRSA in our hospitals Gentamicin-resistant MRSA were first reported in Melbourne in 1976 by Perceval et al. and in Sydney soon thereafter 3. Subsequently, major epidemics of multi-resistant (including gentamicin-resistant) MRSA beginning in the late 197s were reported in Melbourne and Sydney hospitals 6, 7. It was associated with considerable morbidity and mortality and spread easily between institutions. Once established in an institution, MRSA were difficult to control and consequently usually became endemic. Similar epidemics occurred in the other Australian capital cities in the 198s. Vickery et al. found that these new MRSA formed a distinct group by phage typing compared to earlier strains 8. Similarly, Warren Grubb s group was able to demonstrate that this new eastern Australian MRSA (EA-MRSA) was genetically different from MRSA previously isolated in Australia and Europe 9. Early surveys by the Australian Group for Antimicrobial Resistance (AGAR) showed EA-MRSA was endemic in New South Wales/ACT, Victoria, Queensland and South Australia by the mid-198s but not in Western Australia (WA) 1, 11. The control of EA-MRSA in WA is a remarkable feat given the history of MRSA in the remainder of the country. In 198, Pearman et al. reported control of an outbreak of EA-MRSA at Royal Perth Hospital 12. They were able to contain the spread of the outbreak by an exhaustive programme of screening of patients and staff and by transfer of patients to a dedicated isolation facility (after isolation in the ward in which MRSA was detected had failed to control the outbreak). Establishment of stringent infection control procedures based on extensive screening of patients and staff and on notification of MRSA has allowed WA to maintain consistently low rates of healthcare-associated MRSA infection (see also the article by Coombs, van Gessel and Christiansen, page 14). MLST/SCCmec typing of EA-MRSA and its progeny AUS-2 and AUS- 3 have characterised these strains as ST239-MRSA-III. It appears that this clone was first reported in Australia 13 and subsequently spread to the United Kingdom and beyond. It is now found on all inhabited continents and goes by a variety of names including EMRSA-1, the Hungarian strain and the Brazilian strain 14. As EA-MRSA is unique among MRSA strains in Australia in being uniformly resistant to multiple classes of antimicrobials, it is possible to follow trends using multi-resistant MRSA as a surrogate as shown in Figure 1. It can be seen that Brisbane has had a generally downward trend in prevalence since 1989, while Melbourne, Adelaide and Darwin have seen reduced prevalence in recent years. Community MRSA appears Community-acquired MRSA (CA-MRSA) was first reported in WA 126 MICROBIOLOGY AUSTRALIA SEPTEMBER 8
in the early 199s from indigenous people living in different communities in the Kimberley region, 16. Colloquially known as WA-MRSA, CA-MRSA in WA was subsequently identified throughout the State and now accounts for up to 1% of the State s community S. aureus infections. CA-MRSA notification rates per 1, population continue to increase dramatically throughout WA, particularly in the remote country health regions. In 1983, the overall rate of MRSA notifications was 1/1, in the country health regions and 7/1, in the metropolitan health regions. By 6, the State s MRSA notification rate increased to 179/1,, of which 144/1, were CA-MRSA. In the metropolitan heath regions the CA-MRSA notification rate was 134/1,, while in the Kimberley health region the CA- MRSA notification rate had increased 4-fold to 391/1, 17. Molecular analysis of the early strains of CA-MRSA in WA showed these strains were different from MRSA isolated from hospitals in eastern Australia. Most of the CA-MRSA isolates had a similar pulsed-field gel electrophoresis (PFGE) pattern and have subsequently been characterised as ST8-MRSA-IV 18. In the mid 199s a number of laboratories in eastern States noticed the appearance of non-multi-resistant MRSA causing furunculosis in outpatients with an apparent association with Polynesian ethnicity 19. Further studies showed that this epidemic was due to a southwest Pacific (SWP) MRSA strain (ST3-MRSA- IV) identical to that characterised by the Western Samoan phage pattern (WSPP) in New Zealand. This strain carries the genes for Panton-Valentine leukocidin (PVL), an exotoxin that has been associated with furunculosis and necrotising staphylococcal pneumonia. PVL has also been found in numerous other CA- MRSA strains around the world 21. Infection due to the SWP strain in Caucasians were unusual, but in a cluster of cases of CA-MRSA in Caucasians occurred in Ipswich, Queensland. An observational study revealed that these cases were due to a new strain, initially identified as the R pulsotype by PFGE and subsequently known as the Queensland Clone (QLD) (ST93-MRSA-IV) 21, 22. Like the SWP strain, it carried the genes for PVL and has been associated not only with furunculosis but also fatal necrotising pneumonia 23, 24. It has since spread throughout Australia to become one of the dominant epidemic strains of CA-MRSA. Unwelcome arrivals EMRSA- (ST22-MRSA-IV) is an epidemic strain described in the UK and Germany that appears to be very well adapted to the healthcare environment. In Australia it was first reported in WA where it was thought to have been introduced by healthcare workers from the UK. It is characterised phenotypically by non-ß-lactam resistance to ciprofloxacin or to ciprofloxacin and % MRSA 4 4 3 3 1 4 4 3 3 1 4 4 3 3 1 1989 199 Brisbane Sydney Melbourne 1991 1992 1993 1994 199 1996 mmrsa 1997 1998 1999 1 2 3 1989 199 1991 nmmrsa Figure 1. Prevalence of multi-resistant MRSA and non-multi-resistant MRSA in selected Australian cities based on AGAR surveys, 1989-3. MICROBIOLOGY AUSTRALIA SEPTEMBER 8 127 4 4 3 3 1 4 4 3 3 1 4 4 3 3 1 1992 Adelaide Perth Darwin 1993 1994 199 1996 1997 1998 1999 1 2 3
erythromycin and by the lack of urease production. It is now found throughout Australia and is a major healthcare-associated strain in New South Wales 26, 27. In the United States USA3 MRSA (ST8-MRSA-IV), has not only become the predominant cause of community-acquired infection but has also rapidly emerged as a major cause of healthcare-acquired infection. Sporadic reports of this strain have been reported in Australia, Canada, Denmark, Germany, Japan, Switzerland and the United Kingdom. In addition to carrying the PVL genes, USA3 has also acquired an arginine catabolic mobile element (ACME) which does not normally occur in S. aureus but has been detected in Staphylococcus epidermidis 28. It has been hypothesised that the presence of ACME may contribute to the coagulase-negative staphylococci-like traits found in USA3 such as its ability to metabolically alter the local ph on the skin of the host. This change in ph may increase the ability of USA3 to persist on intact skin and consequently facilitate spread by skin contact. Furthermore, USA3 carries a unique PVL sequence variant resulting in an amino acid substitution on the interactive surface of the LukF-PV component and, as a consequence, may enhance PVL function 29. In WA, the number of USA3 MRSA isolated per year since 3 has increased several-fold. Overall, 89 USA3 strains from 78 patients have been characterised, with 92% of these isolates causing skin and soft tissue infections predominantly with abscess formation. Over 6% of patients were younger than 4 years. A total of 76 (8%) isolates were erythromycin-resistant, 3 (39%) ciprofloxacin-resistant, nine (1%) tetracycline-resistant and five (6%) mupirocin-resistant. Of the erythromycin-resistant strains, 88% were clindamycin susceptible (inducible resistance not detected). To prevent USA3 MRSA from becoming established in both the WA community and its hospitals, the WA Health Department has recently commenced a search and destroy policy for all PVL-positive MRSA strains isolated in WA. In addition, in some acute care hospitals, screening has been extended to all high risk and surgical unit admissions. New York Japan (NY-Japan) (ST-MRSA-II) MRSA is a major EMRSA clone that has been reported in several USA States, Canada, Brazil, Mexico, China and Korea. Although infrequently reported in Europe, this clone has been described in Hungary. An outbreak of NY-Japan was recently reported in the south west of WA which involved the area s regional hospital, several community hospitals and long-term care facilities, as well as two teaching hospitals located in the Perth metropolitan area 3. This strain is typically resistant to ciprofloxacin and erythromycin and is urease positive. Sporadic isolates throughout Australia have been reported in recent AGAR surveys. Several other imported MRSA clones have also been isolated in Australia including the healthcare-associated strains EMRSA- 16 (ST36-MRSA-II), EMRSA-17 (ST247-MRSA-I), Irish-1 EMRSA (ST8-MRSA-II) and Irish-2 EMRSA (ST8-MRSA-VI); and several PVL-positive CA-MRSA strains including Taiwan CA-MRSA (ST9- MRSA-V T ), European CA-MRSA (ST8-MRSA-IV) and USA4 (ST1-MRSA-IV). Current trends The MRSA epidemic in Australia can be viewed as a series of concurrent epidemics due to a variety of clones associated with distinct clinical and epidemiological characteristics. There is evidence that the major healthcare-associated epidemic clones, EA-MRSA and EMRSA-, are waning at least in some regions. A recent study in Queensland showed a reduction in EA-MRSA phenotype from 19% of inpatient pus, tissue and fluid S. aureus isolates to 9% between and 6, with a similar decrease for blood culture isolates 31. AGAR data from the hospital survey showed that an increasing proportion of healthcare-associated MRSA infections was due to clones previously associated with community infection particularly in WA, South Australia and Queensland (Figure 2 AGAR, unpublished data) 32. However, MRSA remains the major cause of healthcare-associated infection in Australia and continued efforts in screening and isolation and heightened hand hygiene are warranted. The situation in the community is also changing with the overall prevalence of MRSA increasing while the proportion of clones continues to change. The Queensland clone is now dominant in community MRSA infections in Australia (Figure 3 AGAR, unpublished data). This is of concern as the Queensland clone is PVL positive and has been associated with severe and fatal infections in healthy young adults. These rapid changes in the community have put MRSA on the public health agenda, with WA once again leading the way with a major public health intervention. References 1. Jevons, M.P. (1961) Celbenin-resistant staphylococci. Brit. Med. J. 1, 124-1. 2. Rountree, P.M. and Beard, M.A. (1968) Hospital strains of Staphylococcus aureus with particular reference to methicillin-resistant strains. Med. J. Aust. 2, 1163-1168. 3. Rountree, P.M. (1978) History of staphylococcal infection in Australia. Med. J. Aust. 2, 43-46. 4. Robinson, D.A. and Enright, M.C. (3) Evolutionary models of the emergence of methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 47, 3926-3934.. Perceval, A. et al. (1976) Emergence of gentamicin resistance in Staphylococcus aureus. Med. J. Aust. 2, 74. 6. King, K. et al. (1981) Gentamicin-resistant staphylococci. Lancet 2, 698-699. 7. Pavillard, R. et al. (1982) Epidemic of hospital-acquired infection due to methicillin-resistant Staphylococcus aureus in major Victorian hospitals. Med. J. Aust. 1, 41-44. 8. Vickery, A.M. (1993) Strains of methicillin-resistant Staphylococcus aureus isolated in Australian hospitals from 1986 to 199. Australian Group for Antimicrobial Resistance. J. Hosp. Infect. 24, 139-1. 9. Townsend, D.E. et al. (198) Evolution of Australian isolates of methicillinresistant Staphylococcus aureus: a problem of plasmid incompatibility? J. Med. Microbiol., 49-61. 1. Nimmo, G.R. et al. (3) Antimicrobial resistance in Staphylococcus aureus in Australian teaching hospitals 1989-1999. Microb. Drug Resist. 9, -16. 128 MICROBIOLOGY AUSTRALIA SEPTEMBER 8
cmrsa National:.7% of MRSA ST93-MRSA-IV* ST1-MRSA-IV ST3-MRSA-IV* ST-MRSA-IV ST78-MRSA-IV ST4-MRSA-IV OTHER *PVL positive clones Queensland: 36 isolates % South Australia: 31 isolates New South Wales: 39 isolates 62% 37% 12% Western Australia: 1 isolates ACT: 2 isolates 6% 12% AGAR Tasmania: 1 isolate 3% Victoria: 23 isolates Figure 2. Proportion of CA-MRSA clones among MRSA isolated in the AGAR survey of hospital-acquired S. aureus infection. cmrsa National: 6.1% of MRSA ST93-MRSA-IV* ST1-MRSA-IV ST3-MRSA-IV* ST-MRSA-IV ST78-MRSA-IV ST4-MRSA-IV Northern Territory: 16 isolates 84% Queensland: 46 isolates 7% ST7-MRSA-IV OTHER *PVL positive clones 89% South Australia: 27 isolates 7% New South Wales: 8 isolates 44% Western Australia: 39 isolates ACT: 3 isolates 6% 46% AGAR Tasmania: 3 isolates 23% Victoria: 4 isolates Figure 3. Proportion of CA-MRSA clones among MRSA isolated in the 6 AGAR survey of outpatient S. aureus infection. MICROBIOLOGY AUSTRALIA SEPTEMBER 8 129
11. Turnidge, J. et al. (1989) A national survey of antimicrobial resistance in Staphylococcus aureus in Australian teaching hospitals. Med. J. Aust., 6-72. 12. Pearman, J.W. et al. (198) Control of methicillin-resistant Staphylococcus aureus (MRSA) in an Australian metropolitan teaching hospital complex. Med. J. Aust. 142, 13-18. 13. Townsend, D.E. et al. (1987) The international spread of methicillin-resistant Staphylococcus aureus. J. Hosp. Infect. 9, 6-71. 14. Enright, M.C. et al. (2) The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA). Proc. Natl. Acad. Sci. USA 99, 7687-7692.. Riley, T.V. et al. (199) Changing epidemiology of methicillin-resistant Staphylococcus aureus in Western Australia. Med. J. Aust. 163:412-4. 16. Udo, E.E. et al. (1993) Genetic analysis of community isolates of methicillinresistant Staphylococcus aureus in Western Australia. J. Hosp. Infect., 97-18. 17. Nimmo, G.R. and Coombs, G.W. (8) Community-associated methicillinresistant Staphylococcus aureus (MRSA) in Australia. Int. J. Antimicrob. Agents. 31, 41-41. 18. Coombs, G.W. et al. (6) Methicillin-resistant Staphylococcus aureus clones, Western Australia. Emerg. Infect. Dis.12, 241-247. 19. Collignon, P. et al. (1998) Community-acquired methicillin-resistant Staphylococcus aureus in Australia. Lancet 32, 14-146.. Riley, D. et al. (1998) Methicillin-resistant Staphylococcus aureus in the suburbs. NZ. J. Med, 111, 9. 21. Vandenesch, F. et al. (3) Community-acquired methicillin resistant Staphylococcus aureus carrying Panton-Valentine Leukocidin genes: worldwide emergence. Emerg. Infect. Dis. 9, 978-984. 22. Munckhof, W.J. et al. (3) Emergence of community-acquired methicillinresistant Staphylococcus aureus (MRSA) infection in Queensland, Australia. Int. J. Infect. Dis. 7, 9-267. 23. Peleg, A.Y. et al. () Life-threatening community-acquired methicillinresistant Staphylococcus aureus infection in Australia. Eur. J. Clin. Microbiol. Infect. Dis. 24, 384-387. 24. Risson, D.C. et al. (7) A rapidly fatal case of necrotising pneumonia due to community-associated methicillin-resistant Staphylococcus aureus. Med. J. Aust. 186, 479-48.. Pearman, J.W. et al. (1) A British epidemic strain of methicillin-resistant Staphylococcus aureus (UK EMRSA-) has become established in Australia. Med. J. Aust. 174, 662. 26. Coombs, G.W. et al. (4) Community methicillin-resistant Staphylococcus aureus in Australia: genetic diversity in strains causing outpatient infections. J. Clin. Microbiol. 42, 473-4743. 27. Nimmo, G.R. et al. (6) MRSA in the Australian community: an evolving epidemic. Med. J. Aust. 184, 384-388. 28. Diep, B.A. et al. (8) The arginine catabolic mobile element and Staphylococcal chromosomal cassette mec linkage: convergence of virulence and resistance in the USA3 Clone of methicillin-resistant Staphylococcus aureus. J. Infect. Dis. Apr 21. [Epub ahead of print]. 29. O Hara, F.P. et al. (8) A geographic variant of the Staphylococcus aureus Panton-Valentine leukocidin toxin and the origin of community-associated methicillin-resistant S. aureus USA3. J. Infect. Dis. 197, 187-194. 3. Coombs, G.W. et al. (7) Controlling a multicenter outbreak involving the New York/Japan methicillin-resistant Staphylococcus aureus clone. Infect. Cont. Hosp. Epidemiol. 28, 84-82. 31. Nimmo, G.R. et al. (8) Changing prevalence of methicillin-resistant S. aureus phenotypes in inpatient infections in Queensland Health areas, - 6, as measured by passive susceptibility surveillance. Antimicrobials 8; 21-23 February 8; Sydney, abstract O3. 32. Coombs, G. et al. (7) Staphylococcus aureus Programme (SAP ): Hospital Survey: MRSA Epidemiology and Typing Report. Canberra: Australian Group on Antimicrobial Resistance. Graeme Nimmo is Director of Microbiology for Pathology Queensland and Associate Professor of Molecular Pathology at the University of Queensland. He is currently President of the Australian Society for Antimicrobials, Chair of the Australian Group for Antimicrobial Resistance, and a member of the National Pathology Accreditation Advisory Council and of the Public Health Laboratory Network. His major research interest is the epidemiology of MRSA and he is Chair of the Organising Committee for the 13th International Symposium on Staphylococci and Staphylococcal Infection. Geoffrey Coombs (Please see details on page 114). Food Microbiology Seminar Series: Tales from the Green Book The AIFST, in conjunction with the ASM Food Microbiology SIG, is proud to present a world class, bi-monthly, food microbiology seminar series presented solely by authors of AIFST s award winning Foodborne Microorganisms of Public Health Significance (Green Book). Dates still current are listed below. Wed 1 September 8 Peter Sutherland (NSW-FA) on Ch.13 Listeria Wed 12 November 8 Gary Grohman (Enviro Path) on Ch.22 Viruses Venue Food Science Australia, cnr Creek & Wynnum Roads, Cannon Hill, Brisbane, QLD Who should attend Microbiologists from food industry and consulting laboratories Current / future NATA food microbiology signatories Food industry technical / QA / research staff Food microbiology students wishing to gain further skills and meet future employers Contacts Sofroni Eglezos, Series Co-ordinator & ASM Food Micro SIG Tel: (7) 3848 3622 Email: sofroni@eml.com.au David Pickup, AIFST QLD Branch Chair Tel: (7) 3279 Email: dp@gchahn.com.au Registrations Fax or email Vicki Wallace, AIFST National Tel: (2) 8399 3996 Fax: (2) 8399 3997 Email: aifst@aifst.asn.au 13 MICROBIOLOGY AUSTRALIA SEPTEMBER 8