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Increasing prevalence of methicillin-resistant Staphylococcus aureus in remote Australian communities: implications for patients and clinicians

2019; Elsevier BV; Volume: 51; Issue: 4 Linguagem: Inglês

10.1016/j.pathol.2018.11.015

1465-3931

Isabel Guthridge, Simon Smith, Peter Horne, Josh Hanson,

Streptococcal Infections and Treatments

Staphylococcus aureus is a leading cause of life-threatening community and hospital-acquired infection. Methicillin-resistant S. aureus (MRSA) was initially limited to the hospital environment [healthcare-associated MRSA (HA-MRSA)]; however, in Australia, community-acquired MRSA (CA-MRSA) is now commonly isolated, particularly in Indigenous Australians.1Agostino J.W. Ferguson J.K. Eastwood K. et al.The increasing importance of community-acquired methicillin-resistant Staphylococcus aureus infections.Med J Aust. 2017; 207: 388-393Crossref PubMed Scopus (26) Google Scholar, 2Tong S.Y.C. Bishop E.J. Lilliebridge R.A. et al.Community-associated strains of methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus in Indigenous Northern Australia: epidemiology and outcomes.J Infect Dis. 2009; 199: 1461-1470Crossref PubMed Scopus (87) Google Scholar In the Northern Territory, Western Australia and New South Wales, residence in a remote setting is also an independent predictor of CA-MRSA isolation.1Agostino J.W. Ferguson J.K. Eastwood K. et al.The increasing importance of community-acquired methicillin-resistant Staphylococcus aureus infections.Med J Aust. 2017; 207: 388-393Crossref PubMed Scopus (26) Google Scholar, 2Tong S.Y.C. Bishop E.J. Lilliebridge R.A. et al.Community-associated strains of methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus in Indigenous Northern Australia: epidemiology and outcomes.J Infect Dis. 2009; 199: 1461-1470Crossref PubMed Scopus (87) Google Scholar, 3Riley T.V. Rouse I.L. Methicillin-resistant Staphylococcus aureus in western Australia, 1983–1992.J Hosp Infect. 1995; 29: 177-188Abstract Full Text PDF PubMed Scopus (44) Google Scholar This has important implications for empirical antibiotic regimens in these locations, where clinicians usually have limited access to microbiology laboratory services and are often a long way from sophisticated critical care support. Far North Queensland (FNQ) covers an area of 380,000 km2 in tropical Australia and has a population of approximately 280,000 people, 12% of whom identify as Indigenous Australians. The AUSLAB database records the pathology results of all the hospitals and community clinics in Queensland's public health system. To determine the changing local antibiotic susceptibility of S. aureus, AUSLAB was interrogated to identify all clinical isolates collected in FNQ between 1 January 1997 and 31 December 2016 and their patterns of antibiotic resistance. In the absence of genetic testing, MRSA was defined as in vitro resistance to flucloxacillin; while CA-MRSA was defined as in vitro resistance to flucloxacillin but susceptibility to non-beta-lactam antibiotics.4Turnidge J. Coombs G. Daley D. et al.Australian Group on Antimicrobial Resistance (AGAR) participants, 2000–14MRSA: A Tale of Three Types. 15 Years of Survey Data From AGAR. ACSQHC, Sydney2016Google Scholar The geographical location of each isolate and basic demographic data including patient age, gender, residential address and Indigenous status were recorded. Groups were compared using the chi-squared test; logistic regression analysis was performed using statistical software (Stata version 14.2; StataCorp, USA). Maps were generated using geographic information system software (MapInfo Pro version 15.0; Pitney Bowes, USA) with FNQ divided into eight areas based on key clinical hubs. The Far North Queensland Human Research Ethics Committee provided ethical approval for the study (HREC/16/QCH/112–1085) and waived the requirement for informed consent as the data were retrospective and de-identified. After excluding non-FNQ residents and repeated isolates from the same patient within a 12-month period, S. aureus was isolated on 46,304 separate occasions; 36,802 (79%) were methicillin-sensitive, 8766 (19%) were MRSA, while in 736 (2%) incomplete resistance data precluded classification. Of the 8766 MRSA isolates, 8038 (92%) had antibiograms consistent with CA-MRSA. There was an increase in the prevalence of MRSA over the study period, from 187/786 (24%) in 1997 to 1388/4373 (32%) in 2016 (p for trend <0.001). In some regions this was particularly notable: in the area around Cooktown, MRSA isolates increased from 2/5 (40%) [95% confidence interval (CI) 5–85%] in 1997 to 24/33 (73%) in 2016 (p for trend <0.001) (95% CI 55–87%) (Fig 1). In 2016, 68/3729 (2%) S. aureus isolates were resistant to sulfamethoxazole-trimethoprim; inducible resistance to clindamycin was reported in 368/4350 (9%). There were no cases of vancomycin resistance during the study period. In univariate analysis, MRSA was more commonly isolated in Indigenous patients than non-Indigenous patients [odds ratio (OR) 1.59; 95% CI 1.51–1.68; p<0.001]; in patients aged ≥40 than aged <40 years (OR 1.19; 95% CI 1.12–1.24; p<0.001); and in patients living in metropolitan Cairns than those from a remote setting (OR 1.28; 95% CI 1.22–1.34; p<0.001). There was no difference in univariate analysis between the prevalence among men and women [5296/25972 (21%) versus 4170/20295 (21%), p=0.97; in 217 cases the patient's gender was not available]. In multivariate analysis, MRSA was more common in Indigenous patients than non-Indigenous patients (OR 1.79; 95% CI 1.70–1.90; p<0.001) and in patients living in metropolitan Cairns than those from a remote area (OR 1.46; 95% CI 1.38–1.55; p<0.001). In multivariate analysis, age was no longer an independent predictor of MRSA status, but gender was, with MRSA occurring more commonly in men (OR 1.06; 95% CI 1.01–1.12; p=0.02). While the national prevalence of MRSA amongst all S. aureus isolated in Australia has remained relatively stable at 10–12% over the past 10 years,4Turnidge J. Coombs G. Daley D. et al.Australian Group on Antimicrobial Resistance (AGAR) participants, 2000–14MRSA: A Tale of Three Types. 15 Years of Survey Data From AGAR. ACSQHC, Sydney2016Google Scholar the prevalence in FNQ is presently almost three times this and is continuing to rise. Meanwhile, the current prevalence of MRSA of 73% in the Cooktown region in this study is the highest ever reported in Australia. This increasing prevalence of MRSA is seen in other remote regions around Australia. Across the Northern Territory, the prevalence of MRSA increased from 7% to 24% between 1993 and 2012.5Tong S.Y.C. Varrone L. Chatfield M.D. et al.Progressive increase in community-associated methicillin-resistant Staphylococcus aureus in Indigenous populations in northern Australia from 1993 to 2012.Epidemiol Infect. 2014; 143: 1519-1523Google Scholar A 2017 study examining purulent skin and soft tissues infections around Alice Springs was the first to report MRSA superseding methicillin-susceptible S. aureus (MSSA) as a cause of community onset staphylococcal infections, representing 60% of all isolates.6Macmorran E. Harch S. Athan E. et al.The rise of methicillin resistant Staphylococcus aureus: now the dominant cause of skin and soft tissue infection in Central Australia.Epidemiol Infect. 2017; 145: 2817-2826Google Scholar A similar pattern is seen in New South Wales and Western Australia, with the prevalence and incidence of MRSA higher in remote locations (58% and 3546 per 100,000, respectively).1Agostino J.W. Ferguson J.K. Eastwood K. et al.The increasing importance of community-acquired methicillin-resistant Staphylococcus aureus infections.Med J Aust. 2017; 207: 388-393Crossref PubMed Scopus (26) Google Scholar, 7Coombs G. Pearson J. Robinson O. Western Australian methicillin-resistant Staphylococcus aureus (MRSA) epidemiology and typing report: July 1 2016 to June 30 2017.Dec 2017https://ww2.health.wa.gov.au/∼/media/Files/Corporate/general%20documents/Infectious%20diseases/PDF/HISWA/Annual%20reports/WA_annual_report_MRSA_2016_2017.pdfGoogle Scholar The strongest recorded risk factor for MRSA isolation in this series was an Indigenous background, echoing other Australian studies that have identified a higher rate of MRSA in Indigenous individuals.1Agostino J.W. Ferguson J.K. Eastwood K. et al.The increasing importance of community-acquired methicillin-resistant Staphylococcus aureus infections.Med J Aust. 2017; 207: 388-393Crossref PubMed Scopus (26) Google Scholar, 2Tong S.Y.C. Bishop E.J. Lilliebridge R.A. et al.Community-associated strains of methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus in Indigenous Northern Australia: epidemiology and outcomes.J Infect Dis. 2009; 199: 1461-1470Crossref PubMed Scopus (87) Google Scholar This association between MRSA and Indigenous status has been strongly linked to the marked socioeconomic disadvantage that is seen in many Indigenous communities.8Turnidge J.D. High burden of staphylococcal disease in Indigenous communities.J Infect Dis. 2009; 199: 1416-1418Crossref PubMed Scopus (7) Google Scholar Factors hypothesised to facilitate MRSA transmission in Indigenous populations include overcrowding, higher rates of staphylococcal colonisation, high rates of infective skin disease and, in some cases, unreliable water supply.8Turnidge J.D. High burden of staphylococcal disease in Indigenous communities.J Infect Dis. 2009; 199: 1416-1418Crossref PubMed Scopus (7) Google Scholar Greater exposure to β-lactam antibiotic therapy for recurrent skin and respiratory tract infection has also been hypothesised to increase selection pressure.8Turnidge J.D. High burden of staphylococcal disease in Indigenous communities.J Infect Dis. 2009; 199: 1416-1418Crossref PubMed Scopus (7) Google Scholar It is notable that while a large series from the Northern Territory identified a higher prevalence in remote communities and in women, the converse was true in our series.2Tong S.Y.C. Bishop E.J. Lilliebridge R.A. et al.Community-associated strains of methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus in Indigenous Northern Australia: epidemiology and outcomes.J Infect Dis. 2009; 199: 1461-1470Crossref PubMed Scopus (87) Google Scholar Meanwhile a study from Northern New South Wales reported a higher prevalence in the local Indigenous population, although it also noted that MRSA prevalence has actually been declining in recent years.1Agostino J.W. Ferguson J.K. Eastwood K. et al.The increasing importance of community-acquired methicillin-resistant Staphylococcus aureus infections.Med J Aust. 2017; 207: 388-393Crossref PubMed Scopus (26) Google Scholar This heterogeneity across different populations suggests that while similar underlying trends may exist, there are a variety of social, behavioural and biological factors that impact on MRSA incidence at a local level. It is unclear why MRSA prevalence was higher in males in our region, but it could be explained by higher rates of nasal carriage, differing hand-hygiene behaviour or increased involvement in contact sports.9Humphreys H. Fitzpatick F. Harvey B.J. Gender differences in rates of carriage and bloodstream infection caused by methicillin-resistant Staphylococcus aureus: are they real, do they matter and why?.Clin Infect Dis. 2015; 61: 1708-1714PubMed Google Scholar The finding that MRSA was more common in metropolitan Cairns than in remote, rural communities, contrasts with several other studies that have found residence in a remote community to be a stronger predictor of MRSA carriage.1Agostino J.W. Ferguson J.K. Eastwood K. et al.The increasing importance of community-acquired methicillin-resistant Staphylococcus aureus infections.Med J Aust. 2017; 207: 388-393Crossref PubMed Scopus (26) Google Scholar, 7Coombs G. Pearson J. Robinson O. Western Australian methicillin-resistant Staphylococcus aureus (MRSA) epidemiology and typing report: July 1 2016 to June 30 2017.Dec 2017https://ww2.health.wa.gov.au/∼/media/Files/Corporate/general%20documents/Infectious%20diseases/PDF/HISWA/Annual%20reports/WA_annual_report_MRSA_2016_2017.pdfGoogle Scholar Potential explanations for this observation include the significant mobility of local populations as well as the disproportionate level of socioeconomic disadvantage found in many areas of metropolitan Cairns, which is significantly higher than the regional, state and national averages.10Cairns Regional Council Cairns SEIFA profile by area.https://profile.id.com.au/cairns/seifa-disadvantage-small-areaGoogle Scholar However, it is important to note that while there are differences between our findings and those from other locations, there was even a marked local heterogeneity within this study's cohort, a further reminder that all microbiology is local.11Tong S.Y. Chen L.F. Fowler Jr., V.G. Colonization, pathogenicity, host susceptibility, and therapeutics for Staphylococcus aureus: what is the clinical relevance?.Semin Immunopathol. 2012; 34: 185-200Crossref PubMed Scopus (72) Google Scholar While MRSA rates were high across the region, in 2016 the prevalence of MRSA varied from 20% around Innisfail to 73% around Cooktown. This variation is presumably due again to differences in socioeconomic factors, patterns of social interaction and antibiotic prescription across FNQ.11Tong S.Y. Chen L.F. Fowler Jr., V.G. Colonization, pathogenicity, host susceptibility, and therapeutics for Staphylococcus aureus: what is the clinical relevance?.Semin Immunopathol. 2012; 34: 185-200Crossref PubMed Scopus (72) Google Scholar These findings have major implications for the empirical antibiotic therapy of skin and soft tissue infections and sepsis in FNQ, particularly in remote settings where many patients are managed and where there is frequently limited laboratory support. In the patient presenting with sepsis without a source apparent, vancomycin should be added to empirical regimens. For skin and soft tissue infections, sulfamethoxazole-trimethoprim or clindamycin should be recommended as empirical oral therapy. Clearly, ongoing surveillance is necessary to identify evolving resistance. Stemming the increasing prevalence of MRSA in remote settings has proven to be challenging. Infection control measures including hand hygiene are effective for reducing hospital-acquired MRSA but are more difficult to implement in the community setting. A focus on hand hygiene has the advantage of addressing other pathogens simultaneously, although other measures including case finding and eradication would be required in patients with recurrent infections. Simple hygiene messages should be reinforced, although as the infection appears to be a marker of socioeconomic disadvantage, public health policies that address this fact at a regional and national level are more likely to have an impact on both MRSA prevalence and health outcomes generally. The authors state that there are no conflicts of interest to disclose.