Centre for Research Excellence in Minimising Antibiotic Resistance in the Community (CRE-MARC)

Who we are

CRE-MARC (Centre for Research Excellence in Minimising Antibiotic Resistance in the Community) is an NHMRC-funded Centre for Research which started in Nov 2018 (for 5 years), at $2.5m

It builds on CREMARA (The Centre for Research Excellence in Minimising Antibiotic Resistance for Acute Respiratory Infections) which was funded by the NHMRC in 2012. This second CRE that is building on the achievements of CREMARA in acute respiratory infections and extends this research into a second phase of implementation and new work in urine and skin infections.

What CREMARA achieved

The team achieved 91 publications (a combination of articles that provided new knowledge, along with articles that emphasised research translation and practice and policy implications). Many of these articles generated knowledge about effective interventions that general practitioners (GPs) can adopt to reduce their prescribing of antibiotics for acute respiratory infections (ARIs). Additional funding (such as via NHMRC project grants scheme) was obtained to conduct large projects, such as nation-wide cluster randomised trials in general practice. The CREMARA team held two national summit meetings. The 2017 National Roundtable meeting involved presentations from and discussion with the United Kingdom’s Chief Medical Officer Dame Sally Davies, Australia’s Chief Medical Officer Prof Brendan Murphy, and key stakeholders from numerous federal and state government departments, agencies, and other research groups, and a report published in the MJA, and ongoing action planned developed.

The outputs from CREMARA have influenced policy in Government (eg Australian Strategic and Technical Advisory Group on Antimicrobial Resistance, ASTAG), Australian Commission on Safety and Quality in Health Care (ACSQHC); and professional bodies (eg Royal Australian College of GPs (RACGP) and other colleges). CREMARA has also strongly contributed to building research capacity, with 11 PhD scholars and post-doctoral research fellows, and >10 clinician-researchers developing skills in research and research translation in the important field of community antibiotic resistance research. One CREMARA post-doctoral research fellow has recently commenced an academic position in Denmark continuing to work in antibiotic resistance in the community and collaborate with our team.

What is needed next

CRE-MARC. Three major obstacles remain to reducing antibiotic use in Australian primary care:

  1. the poor adoption of several effective interventions for improving ARI prescribing, which emphasises that the next steps should be implementation research focussed on improving uptake of these interventions into practice;
  2. the need to broaden the focus beyond minimising antibiotic use in just acute respiratory infections (ARIs) and to include the two other major antibiotic indications in primary care – skin and soft-tissue infections (SSTIs) and urinary tract infections (UTIs); and
  3. the well-known, but little understood, problem of very high use of antibiotics in Residential Aged Care Facilities (RACFs).

The antibiotic resistance crisis will have two substantial public health consequences unless reversed soon: avoidable deaths, and hampered medical care. The first consequence has begun: extrapolating from overseas data1about 1,600 people in Australia each year die directly from antibiotic resistance. The avoidable mortality will get steadily worse, until 2050, when deaths from currently treatable infections may overtake total cancer deaths.1 The second consequence is the risk that antibiotic resistance poses to now-routine high technology medical care.3 Without reliable antibiotic prophylaxis, procedures such as chemotherapy, bone marrow transplant, much major surgery (including joint prostheses) and invasive diagnostic procedures (including cardiac catheterisation), will become too dangerous to perform.1,4 Many aspects of medical care will retreat into the pre-antibiotic era of the 1930s. The economic consequences of this are catastrophic, dominating even the effects of antibiotic resistance on health, prompting the Chief Medical Officer of the United Kingdom’s National Health Service to declare this threat every bit as serious as terrorism.4, 5

Governments are attempting to provide incentives for the pharmaceutical industry to generate new classes of antibiotics,5 but resistance has been an inevitable consequence of every new class of antibiotic developed to date. Since withholding antibiotics results in the return of susceptibility in the microbiome6conservation of antibiotics is more likely to be successful at extending the life of the existing antibiotics, and any developed in the future.4 This is the focus of our approach.

For many GPs working in the community this unfolding crisis is not directly obvious. Yet GPs prescribe most of the antibiotic tonnage consumed by humans in Australia.7 Their prescribing of antibiotics is now creating resistance entering the tertiary (hospital) care sector, Figure 1. Exact data are not available in Australia, but in Denmark and Sweden (low community antibiotic-prescribing countries), 90% of antibiotics for human use are prescribed outside hospitals, and 65% by GPs.8,9Reducing antibiotic usage allows resistance to dissipate6, as the unnecessary metabolic burden of producing resistance genes in the absence of antibiotics puts these organisms at a selective disadvantage.

Some areas of primary care are ripe for this – especially prescribing for common ARIs, for which a wealth of evidence shows that the benefits of antibiotics are small, harms are common, and that not using them is safe.10,11 Other areas of high prescribing are for urinary (UTIs), and skin-and-soft-tissue infections (SSTIs), which therefore is a focus in Stream 3. Other countries, such as Sweden and the Netherlands use less than half the quantity per capita of antibiotics than Australia7 with no increase in serious infections.9

  1. World Health Organisation. Antimicrobial resistance: global report on surveillance. . 2014.
  2. Centre for Disease Dynamics EP. The state of the world’s antibiotics. 2015.
  3. WHO. Critically Important Antimicrobials for Human Medicine. Geneva: 2011.
  4. Davies DS, Grant J, Catchpole M. The drugs don’t work: a global threat: Penguin UK; 2013.
  5. O’Neill J, Davies S, Rex J, White LJ, Murray R. Antimicrobial Resistance: Tackling a crisis for the health and wealth of nations. London: HM Government (UK) and Wellcome Trust, 2014.
  6. Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ. 2010;340:c2096.
  7. Australian Commission on Safety and Quality in Health Care (ACSQHC). AURA 2016: first Australian report on antimicrobial use and resistance in human health Sydney: ACSQHC, 2016.
  8. Danish Integrated Antimicrobial Resistance Monitoring and Research Programme. DANMAP. Use of Antimicrobial Agents and Occurrence of Antimicrobial Resistance in Bacteria from Food Animals, Food and Humans in Denmark 2015.
  9. Tyrstrup M, Beckman A, Mölstad S, Engström S, Lannering C, Melander E, et al. Reduction in antibiotic prescribing for respiratory tract infections in Swedish primary care- a retrospective study of electronic patient records. BMC Infectious Diseases. 2016;16(1):709.

Collaborators

Our team has a wide range of collaborations nationally and internationally that we will use and strengthen to pursue the CRE-MARC vision of improving antibiotic use in the community by: generating new knowledge, translating knowledge to improve clinical care and reduce antibiotic resistance. These collaborations include those between the current CREMARA team, the RACGPTherapeutic Guidelines Antibiotic Guidelines, the National Prescribing Service, PHNs, universities, research institutes, policy groups and the departments of health.

Chief Investigators

Professor Chris Del Mar
Professor Paul Glasziou
Professor Tammy Hoffmann
Associate Professor Elaine Beller
Associate Professor David Looke
Doctor Sue Phillips
Professor Mieke van Driel

What CRE-MARC is doing

1. Community Antibiotic Stewardship implementation studies with several Primary Healthcare Networks (PHNs) and Practice-Based Research Networks, culminating in a randomised trial of interventions known to be effective at reducing antibiotic prescribing;
2. Skin and soft-tissue infections (SSTIs) and urinary tract infections (UTIs) – generating and synthesising evidence about antibiotic benefits and harms for these conditions (which together with ARIs covers >85% indications for antibiotic use in primary care) and developing interventions to improve appropriateness of antibiotic use for them;
3. Residential Aged Care Facilities – tackling the problem of very high antibiotic use by exploring the reasons and using information about enablers and barriers to design interventions that improve the appropriateness of antibiotic use;
4. GP registrars – developing and evaluating targeted educational interventions; and
5. Addressing other important, but neglected, questions about antibiotic resistance by conducting both primary studies and systematic reviews of the literature.

Over-arching all these streams, CRE-MARC is strongly contributing to the training and development of a new set of researchers who are able to continue and lead research in this crucial area of population health concern, through training of PhD students, post-doctoral research fellows, and clinician-researchers.

Staff