The respiratory tract

November 2012

Up front

Addressing antibiotic resistance

Focusing on acute respiratory infections in primary care

Volume 41, No.11, November 2012 Pages 839-840

Chris Del Mar

Paul Glasziou

John Lowe

Mieke van Driel

Tammy Hoffmann

Elaine Beller

We have been aware for decades – perhaps as a somewhat far-off theoretical problem – that antibiotic resistance is a threat to healthcare worldwide. However, the crisis is now here and very real. Each year in Europe alone, 25 000 deaths are directly attributed to antibiotic resistance.1 New antibiotics are not being produced fast enough, and resistance means we are running out of antibiotics of last resort.

The implications of antibiotic resistance for the future of healthcare are frightening. Quite apart from serious infections (such as pneumonia and sepsis), which are now managed routinely with antibiotics, we face huge challenges for much of our medical ‘high technology’ (such as joint replacement, chemotherapy and cardiac catheterisation), which is dependent on antibiotic ‘cover’ (prophylaxis). Risk benefit comparisons will change.

Of course the solution is, on the face of it, quite simple. Stop prescribing antibiotics. However, this is difficult to achieve for many reasons. At the core is the problem of the ‘failure of the commons’:2 resistance is a shared, delayed and remote problem while the patient’s wellbeing is ‘mine’, immediate and proximal.

Acute respiratory infections (ARIs) comprise 10% of primary care consultations in Australia and an antibiotic is prescribed in 58% of cases.3 For example, in acute otitis media (which accounts for 7% of all general practitioner consultations with children in Australia), antibiotics are prescribed for 82.3% of consultations,4 despite systematic reviews in the 1980s showing the benefit of antibiotics is very small. Extrapolating from overseas, Australians consume an estimated 1000 tonnes of antibiotics per year,5 most prescribed in primary care rather than through hospital or specialist care.

Prescribing antibiotics in primary care is associated with a doubling of the odds (OR 1.95, 95% CI: 1.1–3.5) of isolating antibiotic resistance commensal organisms 2 months later.6

Following publication of some seminal systematic reviews in the 1980s and 1990s, antibiotic use for these conditions began to fall and it looked as if with time the crisis would pass. However, for the past two decades, antibiotic use has plateaued at a level much higher than in northern European countries. This means that relying solely on interventions that minimise resistance by reducing antibiotic prescribing is risky and that a broader front of attack is necessary.

Both clinician and patient-related factors are important in antibiotic resistance. It is difficult to dissuade clinicians from overprescribing: they wish to support their patients who have an ARI, even when they believe that antibiotics are only minimally effective, perhaps because their attitude is ‘my patient wants me to do something’.7 However, patients with a sore throat who hope for antibiotics when attending a consultation actually often want symptom relief, which could be better provided by analgesics than antibiotics.8 Perceived patient expectations are also important. General practitioners are nearly three times more likely to prescribe antibiotics if they believe patients expect them.9 Other clinician-related factors include concern about diagnostic uncertainties in ARIs and missing important bacterial illnesses (such as pneumonia and meningitis) and downstream commercial incentives in a fee-for-service environment where consultations with prescribed antibiotics are easier, terminated more quickly and effectively, and result in patients being 40% more likely to re-consult for future ARIs.10

Patients (or parents) often have misperceptions about the benefits and harms of antibiotics. Some parents of children with acute otitis media assume that antibiotics are the best and only way to treat the illness, do not perceive antibiotics to have any harms, and do not entertain the idea of treatment that does not include antibiotics. Patients with an ARI often self-medicate with antibiotics that they (or a family member) already have at home, with little or no awareness of the individual and population harms of doing so – another contributor to resistance.11

We hypothesise that most clinicians and most patients do not understand that population antibiotic resistance can be reversed – as data from Iceland show.12

Few patients or clinicians know about person-to-person transmission of resistance genes. Bacteria from different species commonly exchange genetic material, including ‘resistance’ genes. As humans harbour about 1014 bacteria (ie. 10 for every human cell), antibiotics will affect nonpathogenic bacteria (commensals) as much as pathogenic. Therefore, there is a huge opportunity for resistance genes to colonise other people using normal contamination transmissions: in other words, resistance can be transmitted in the same way as infection (Figure 1). Therefore, interventions that reduce acute respiratory infection transmission (known to be effective13) should also reduce resistance gene transmission.

Figure 1. Causes of antibiotic resistance

Figure 1. Causes of antibiotic resistance

It is timely therefore, that the award of National Health and Medical Research Council multidisciplinary Centre for Research Excellence funding has provided the opportunity for a group of us to generate new knowledge to support the superb efforts of the National Prescribing Service, which has been addressing antibiotic and other prescribing challenges. These areas for new knowledge generation are outlined in Table 1.

Table 1. Areas for new knowledge generation
Thinking more critically about harms and benefits of antibiotics for acute respiratory infections. We have heard much about the paucity of benefits of antibiotics, but perhaps insufficient about the harms (the thrush, rashes, gastrointestinal upsets as well as more serious adverse effects) which need to be introduced into the riskbenefit equation
Adopting higher rates of hand washing to reduce person-to-person infection with both acute respiratory infections and resistance genes (carried by normal commensals)
Addressing the labelling of antibiotic packaging better: we have packet sizes that allow for unused doses or new packets that have to be broached
Increasing the uptake of delayed prescribing in Australia. This 'safety net' works well at reducing antibiotic consumption overseas, but has never been trialled in Australia
Addressing the problem as resistance genes rather than infectious agents. The issue here is that resistance can be transmitted via gene transfer from pathogens to commensals and back again. How resistance is spread through the community is poorly understood, although we know that it is generated easily enough with antibiotic use
Modelling all these approaches to estimate which ones are likely to yield the best returns in reducing antibiotic resistance

We will be seeking practices interested in joining us in undertaking research projects on these issues. For more information or to express your interest in participating in this research please email CREMARA@bond.edu.au.

Conflict of interest: none declared.

References

  1. Editorial. Urgently needed: new antibiotics. Lancet 2009;374:1868.
  2. Hardin G. The tragedy of the commons. The population problem has no technical solution; it requires a fundamental extension in morality. Science 1968;162:1243–8.
  3. Pan Y, Henderson J, Britt H. Antibiotic prescribing in Australian general practice: how has it changed from 1990–91 to 2002–03? Respir Med 2006;100:2004–11.
  4. Taylor PS, Faeth I, Marks MK, et al. Cost of treating otitis media in Australia. Expert Rev Pharmacoecon Outcomes Res 2009;9:133–41.
  5. Millet Medina FJ, Gracia Aguirre S, Madridejos Mora R, Sole Lopez J. [Antibiotic consumption (1993–1996) in primary care in a health area with a high rate of bacterial resistance]. Aten Primaria 1998;21:451–7.
  6. Hay AD, Thomas M, Montgomery A, et al. The relationship between primary care antibiotic prescribing and bacterial resistance in adults in the community: a controlled observational study using individual patient data. J Antimicrob Chemother 2005;56:146–53.
  7. Doust J, Del Mar C. Why do doctors use treatments that do not work? BMJ 2004;328:474–5.
  8. van Driel ML, De Sutter A, Deveugele M, et al. Are sore throat patients who hope for antibiotics actually asking for pain relief? Ann Fam Med 2006;4:494–9.
  9. Little P, Dorward M, Warner G, Stephens K, Senior J, Moore M. Importance of patient pressure and perceived pressure and perceived medical need for investigations, referral, and prescribing in primary care: nested observational study. BMJ 2004;328:444.
  10. Little P, Gould C, Williamson I, Warner G, Gantley M, Kinmonth AL. Reattendance and complications in a randomised trial of prescribing strategies for sore throat: the medicalising effect of prescribing antibiotics. BMJ 1997;315:350–2.
  11. Grigoryan L, Burgerhof JG, Haaijer-Ruskamp FM, et al. Is self-medication with antibiotics in Europe driven by prescribed use? J Antimicrob Chemother 2007;59:152–6.
  12. Arason VA, Sigurdsson JA, Erlendsdottir H, Gudmundsson S, Kristinsson KG. The role of antimicrobial use in the epidemiology of resistant pneumococci: a 10-year follow up. Microb Drug Resist 2006;12:169–76.
  13. Jefferson T, Del Mar C, Dooley L, et al. Physical interventions to interrupt or reduce the spread of respiratory viruses. Cochrane Database Syst Rev 2011;CD006207.

Correspondence afp@racgp.org.au

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