Antibiotic resistance - a call to arms for primary healthcare providers

Seventy years after the discovery of the first antibiotics, resistance to these life-saving drugs has become a significant global public health issue. In 2007, there were around 25,000 deaths because of antibiotic-resistant infections in Europe 1; in the US, that figure was nearly 100,000, with an estimated cost of US$21–34 billion 2. Antibiotic-resistant bacteria affect most branches of medicine and resistance to antibiotics can potentially complicate the management of even the mildest infection 1. Immunocompromised patients are particularly vulnerable to multidrug-resistant bacterial infections as a consequence of their treatments for underlying illnesses 1. A worst-case scenario is that patients may be unable to receive chemotherapy or undergo routine operations (e.g. hip replacement), as the benefit of the treatment might no longer outweigh the risk of being inadequately protected from infection. Longer term consequences for the global population, their economy and nutrition may also result, not least from untreatable infections in livestock and subsequent travel and trade restrictions becoming necessary to reduce the spread of pathogens 3. Until now, new antibiotics have been developed to replace older, increasingly ineffective ones. However, no new class of antibiotics has been discovered since 1987, leaving a void on one side of the battle. Bacterial mutation appears to be overtaking human innovation, and we do not yet know whether any of the new drugs currently in the development pipeline will be effective against new mutations of bacteria, making a pandemic a real possibility 3. The growing gap between infections caused by multidrug-resistant bacteria and the decline in research and development of new antibiotics is now threatening to take us back to a pre-antibiotic era with simple infections becoming untreatable, or even fatal, so negating the healthcare advances made in the last 100 years, unless there is a global effort to contain the threat of antibiotic resistance 4. The evolution of antibiotic resistance together with the lack of new antibiotics being developed makes the emergence of untreatable, multi-drug resistant infections ever more likely 4. Antibiotic usage and antibiotic resistance rates vary widely between countries. In many countries, resistance rates have more than doubled in the past 5 years 5, and antibiotic-resistant bacteria have recently been found in Antarctic animals and water samples 3. Within the EU, around 400,000 patients contract infections that are resistant to multiple antibiotics every year, and significant resistance to last-line antibiotics is beginning to emerge in several countries 6. Antibiotic resistance can lead to hospitalisation, prolonged illness, increased risk of complications, and it is estimated that complications associated with antibiotic resistance cost €9 billion annually in Europe 7. Rapidly increasing resistance rates are of particular concern in developing countries, where respiratory disease has overtaken diarrhoea as the most frequent cause of death in children 8. The direct relationship between antibiotic overuse and the rate of antibiotic resistance will increasingly limit treatment options if it continues at current levels. Reasons for overprescribing include diagnostic uncertainty, cultural or personal habits and apparent patient pressure, although recent data suggest that the latter may be over-estimated; one study has shown that most patients who ask doctors for an antibiotic actually just want pain relief 9. The challenge we face is therefore to achieve a meaningful reduction in unnecessary antibiotic use while maintaining effective management of bacterial infections. An issue that illustrates this point is that of respiratory tract infections (RTIs), which are the most commonly treated acute problem seen in primary care 10. Although complications of upper respiratory tract infections (URTIs) are now uncommon and antibiotics are appropriate for only a small number of patients 8, primary care physicians continue to prescribe them – in the UK, 60% of all antibiotics prescribed are for patients with respiratory infections 11. Patients who are prescribed an antibiotic in primary care for a respiratory infection can develop bacterial resistance to that antibiotic, which may persist for up to 12 months. This effect not only increases the number of organisms resistant to first-line antibiotics, but also creates the conditions for increased use of second-line antibiotics in the community 12. Patients who are prescribed antibiotics unnecessarily for self-limiting infection may incorrectly believe the antibiotics did in fact treat their infection, which may incentivise them to request antibiotics in the future. A survey of Russian households found that 83.6% of families store antibiotics at home for systemic use, moreover the major indication for self-medication with antibiotics was acute viral RTIs (12.3% of total indications) 13. The problem of antimicrobial resistance is widely recognised as an urgent issue 14 and global initiatives to counteract the threat of antibiotic resistance have been initiated by the Infectious Diseases Society of America; however progress in development of new antibiotics has been slow 14. There have been campaigns in many countries to educate both the public about appropriate use of antibiotics and the community and healthcare providers about antibiotic stewardship. These campaigns may help to promote more careful use of antibiotics, at least in high-prescribing countries 15. However, the challenge remains in how to shift the focus from a recognition that antibiotic resistance is a global health imperative to the implementation of measures that facilitate change at a local level 16. While the overuse of antibiotics is recognised as a major factor in development of antibiotic resistance, the implementation of measures that will help change behaviour, of both prescribers and patients, requires education and commitment at all levels. To change behaviour, simultaneous and consistent intervention at many levels is required, and three essential conditions must be met: capability, opportunity and motivation 17. Education has been identified as particularly important. It is now crucial that teaching focuses on all necessary aspects of microbiology, infectious diseases and clinical pharmacology, with emphasis on the principles of prudent prescribing 18. Effective action requires increased awareness of antibiotic resistance as a priority at national and international levels 19. An overarching framework is needed that can be adopted across countries to create a consistent approach to change behaviour and provide the flexibility to address local issues 8. The multi-disciplinary global respiratory infection partnership (GRIP) is committed to creating such a framework that will encompass a non-antibiotic, pro-symptomatic relief policy approach to RTIs, underpinned by guidance on appropriate antibiotic use and advice for prescribers, pharmacists and other pharmacy staff, together with advice for patients on self-management strategies 16. A change in the empiric prescribing and unsolicited use and sale of antibiotic treatment in general practice and communities around the world is one area being targeted by GRIP, and is reported in two articles in this issue (Essack and Pignatari (20), and van der Velden et al. (21). GRIP emphasises a need to focus on antibiotic resistance at the local community level, where the treatment of URTIs, such as sore throat, is particularly relevant. GRIP has developed the tools to build an international framework for the non-antibiotic management of RTIs that specifically addresses the physician–patient interaction 8, and brings together policy on antibiotic stewardship, guidance on appropriate antibiotic prescribing, patient participation combined with evidence-based symptomatic management of RTIs, and guidance on strategies for effective communication between physicians and patients 8. Future GRIP activities will be focused on helping countries meet the challenge of antibiotic resistance 16. Publication of this supplement was supported as part of an unrestricted educational grant by Reckitt Benckiser Group PLC. Editorial assistance during the development and revision of this manuscript was provided by Mash Health Limited and supported by Reckitt Benckiser Group PLC. The authors provided substantial contributions to the development and revision of the manuscript and approved the final version of the manuscript. Publication of this supplement article was supported as part of an unrestricted educational grant by Reckitt Benckiser Group PLC. Editorial assistance during the development and revision of this manuscript was provided by Mash Health Limited and supported by Reckitt Benckiser Group PLC.