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Antimicrobials: challenging resistance

Altering general practice prescribing can play a significant role in combating antibiotic resistance.

Penicillin, the world’s first antibiotic, or ‘bacteria killer’ as it was originally known, was discovered by Scottish doctor and bacteriologist Alexander Fleming in 1928 and was being produced on a commercial scale by the 1940s. But, not long after accepting a Nobel Prize in 1945, Dr Fleming was already predicting the danger of antibiotic resistance from overuse of such medications.1

According to Prof Chris Del Mar, Professor of Public Health at Bond University on the Gold Coast, this situation – antibiotic resistance – has now become a critical concern in Australia and throughout the world.

‘The antibiotic crisis has come,’ he told Good Practice. ‘We are getting reports from all around the world of multi-resistant organisms; so resistant to every antibiotic we know.’

The consequences of this development could be described as catastrophic.

‘[It could mean a return] to the pre-antibiotic era, when people died of pneumonia, and the postman got a prick on his finger from attending his rosebushes and died of septicaemia,’ Prof Del Mar said.

Such a situation would also result in significant downstream effects, with an impact on public health.

‘When you’re working in a hospital and treating patients with cancer who are vulnerable to infection, you don’t want antibiotics that don’t work,’ Prof John Turnidge, lead for the Australian Commission on Safety and Quality in Health Care’s (ACSQHC) National Antimicrobial Utilisation Surveillance Program, told Good Practice.

Medical procedures currently considered routine may also become significantly riskier for the patient.

‘As well as direct deaths from antibiotic resistance, you’d also have the inability to use antibiotic cover for high-risk procedures, which we now take as standard care,’ Prof Del Mar said. ‘That includes things like joint replacements, for example. So that means a lot of orthopaedic surgery would be too dangerous to do.’

Because there are very few new antibiotics under development for general use,2 large-scale inquiries into the phenomenon of antibiotic resistance, such as the UK’s Tackling drug-resistant infections globally: Final report and recommendations, have suggested that a major part of the solution is to reduce unnecessary antibiotic prescriptions across hospitals and primary care.3

‘Antibiotic resistance only happens if you use the antibiotics,’ Prof Del Mar said. ‘If you don’t use them, the competitive environment for the bacteria means the bacteria are at a disadvantage if they carry resistance genes.’

Achieving a reduction in antibiotic prescribing would involve a combination of patient education, finding alternatives to antibiotics, and ensuring antibiotics are only prescribed when they will be genuinely effective.

Antibiotics in general practice

While many of the most common antibiotic resistance scenarios occur within hospitals, general practice prescribing has also contributed to the issue.

‘GPs’ prescribing habits inevitably have a large effect on antibiotic use in Australia, just through volume of patients seen,’ Dr Justin Coleman, GP and Chair of the RACGP working group on NPS MedicineWise’s ‘Choosing Wisely Australia’ initiative, told Good Practice.

The ACSQHC’s Antimicrobial Use and Resistance in Australia (AURA) project, which explored the impact of general practice antibiotic prescribing in a 2016 report found that GPs generate 88% of antibiotic prescriptions in Australia.4

According to Prof Turnidge, a member of the AURA project reference group, the report contained a number of other concerning statistics.

‘Other figures that troubled us most were on the Pharmaceutical Benefits Scheme [PBS], which covers about 95% of all antibiotic scripts within the community,’ he said. ‘In 2014, 46% of Australians took at least one course of antibiotics, which is a mind-boggling figure.’

Dr Coleman placed Australia’s prescribing figures into a global context.

‘In terms of antibiotic prescribing, Australia ranks lower than the average OECD [Organisation for Economic Cooperation and Development] countries,’ he said. ‘In particular, we compare poorly to a lot of European countries. Notably, [Australia prescribes] more than Scandinavia, which has done very well with reduced targeted antibiotic prescribing for years.’

According to Prof Del Mar, these rates of over-prescribing emerged from a widespread ‘better safe than sorry’ approach from earlier days in general practice, when resistance wasn’t as much of a problem. He used the case of a sore throat as a common example.

‘We know a lot of sore throats are caused by streptococcus and that you can get nasty consequences from streptococcus, including acute rheumatic fever and acute glomerulonephritis,’ he said. ‘We also know that streptococcus is very sensitive to penicillin, so it seemed very sensible to cover it with penicillin.

‘That was standard practice in all the textbooks to stop these side-effects.’

Prof Turnidge feels this type of practise has also led to patients often expecting prescriptions for antibiotics when they visit their GP.

‘An unwritten bond has been built up [between doctor and patient] in Australia that’s led to this dizzying spiral of increasing antibiotic use,’ he said.

This, Prof Turnidge believes, can be exacerbated by a fear of losing patients.

‘General practice is a private business and you’ve got to keep your customer satisfied, so to speak,’ he said. ‘There’s always a concern that if you don’t write the script, the patient will go to the GP down the road or to the 24-hour clinic to get it.’

Evidence-based

Dr Coleman believes a doctor’s decision regarding whether or not to prescribe should be made according to the evidence. He used Choosing Wisely’s guidelines against overusing antibiotics to illustrate the point.

‘Choosing Wisely wouldn’t make these recommendations based just on the increased risk of resistance, because if they did a whole lot of good for the individual receiving the antibiotics would outweigh the broader harm done by increasing resistance,’ he said.

‘But what the evidence shows in so many of these instances is that … the difference antibiotics make is often quite disappointing.’

Nor is the risk of further complications from infection enough to justify many prescriptions.

‘For a GP to see a single case of acute rheumatic fever arising from sore throat, for example, would be something like one in 10 GPs’ professional lifetimes,’ Prof Del Mar said. ‘You’ve got to see a lot of sore throats to stop that one case, and it’s much the same for glomerulonephritis.

‘So the symptoms themselves aren’t a good cause, and the infective symptoms are much the same.’

While there are obviously cases in which antibiotic prescriptions are well-warranted, recent research has also shown that doctors who are considered ‘cautious’ prescribers actually have the same rate of adverse outcomes from infections as ‘enthusiastic’ prescribers.5

‘I think what that reflects is that GPs who are cautious prescribers still give antibiotics where they are needed,’ Dr Coleman said. ‘The difference lies in the larger numbers of people who probably don’t need the antibiotics.’

It should also be noted that antibiotics themselves can have adverse effects.

‘Doctors often forget to tell patients that antibiotics actually carry some harms with them,’ Prof Del Mar said. ‘Things like rashes, bellyache and diarrhoea, or thrush.

‘If you do the empirical work, you can see the harms that you get from antibiotics are much the same as the benefits, at the same sort of rate.’

Alternative strategies

As Prof Del Mar explained, ‘GPs got used to using antibiotics and patients got used to expecting them.’ How can doctors counter the situation?

One method is to intervene at the prescribing stage. Prof Turnidge described a strategy that has been used in the UK called ‘delayed prescribing’, in which a script is written for antibiotics but the patient is asked not to fill it for 48 hours.

‘It does work in the sense that only a third of patients are ever likely to fill the script. That’s the evidence we have from the UK,’ he said. ‘But the irony of that is if you need an antibiotic, you actually need it now. Waiting two days isn’t a great idea.

‘But we would continue to promote it as a strategy because it starts to send a message that, “No, you don’t need antibiotics now”.’

Another prescribing strategy being considered by the ACSQHC is introducing scripts that expire within two weeks of being written.

‘That’s quite important, because we now have information about how many antibiotics prescriptions are filled weeks, or even months, after they were written, which means that people didn’t fill it then and there, but used it later off their own bat for some other indication,’ Prof Turnidge said.

There are also a variety of different options under development in the global effort to combat antibiotic resistance.3

‘People are looking at alternatives to achieve what they need,’ Prof Turnidge said. ‘For instance, infection control strategies or chemicals other than antibiotics that can achieve the same aim.’

All agreed, however, that patient education within consultations is one of the most effective strategies for GPs.

‘It is about having that conversation with the patient at the time, getting them to understand that antibiotics are actually rather precious things and should only be prescribed when doctors really think the patient is likely to benefit,’ Prof Turnidge said.

Prof Del Mar believes it is also important to personalise the message of antibiotic resistance for the individual.

‘I mention [to patients] that if you take antibiotics and then subsequently get an infection like meningitis or pneumonia, there’s good data to show that if you’ve got resistance on board, getting on top of those very serious infections can be more difficult,’ he said.

However, Prof Turnidge acknowledged the often-pressured nature of general practice and the importance of providing support for GPs.

‘GPs are busy. They’ve got a waiting room full of people and it’s much easier for them to write a script than sit there and explain why they’re not doing it,’ he said. ‘So we’ve somehow got to facilitate that interaction and make it worth their while.

‘That’s where we need to fix the problem, right at that critical point.’

Prof Del Mar is also keen to ensure GPs aren’t burdened by such explanations.

‘We need to provide GPs with quick ways of communicating that quite complicated information to patients, so it doesn’t make the consultation any longer,’ he said.

Although it may initially be difficult to change patient expectations, Dr Coleman believes good research provides a firm foundation for change.

‘If it is good-quality evidence, it has to change our prescribing patterns, otherwise we’re just basing [our decisions] on what has always been done,’ he said.

References

  1. Penicillin’s finder assays its future. The New York Times. 26 June 1945: 21.
  2. The Pew Charitable Trusts. Tracking the pipeline of antibiotics in development. Philadelphia, USA: The Pew Charitable Trusts, updated May 2016. Available at www.pewtrusts.org/en/research-and-analysis/issue-briefs/2014/03/12/tracking-the-pipeline-of-antibiotics-in-development [Accessed 27 September 2016].
  3. Review on antimicrobial resistance. Tackling drug-resistant infections globally: Final report and recommendations. United Kingdom: Review on antimicrobial resistance, 2016.
  4. 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.
  5. Gulliford M, Moore, M, Little P, et al. Safety of reduced antibiotic prescribing for self limiting respiratory tract infections in primary care: cohort study using electronic health records. BMJ, 2016; 354:i3410.