When it comes to the spread of antibiotic resistance, there is no shortage of dire predictions. Phrases such as “a global public health and environmental catastrophe” (US Institute of Medicine) and “a doomsday scenario” (WHO) are commonplace. Indeed, ever since the advent of penicillin, there have been concerns about this phenomenon. Alexander Fleming himself sounded a warning at the end of his Nobel lecture in 1945: “There is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant”.
The factors behind the development of antimicrobial resistance are well known and are generally drummed into healthcare professionals throughout their training and careers. Yet the misuse of antibiotics remains widespread. A 2011 article in JAMA suggested that up to 50% of antibiotic use is unnecessary or inappropriate.[1] Often overlooked are contributory factors outside of human healthcare. A US Congresswoman, who is also a microbiologist, has calculated that four fifths of antibiotics used in the US are given to livestock, often to completely healthy animals, creating yet more opportunities for the development of resistance.[2]
In 2011, antibiotic resistance was the theme of World Health Day, which adopted the slogan “No action today, no cure tomorrow”. This followed publication of details of the spread of a gene called NDM-1 (New Delhi metallo-beta-lactamase) to different species of bacteria, making them resistant to nearly all of the carbapenems, the most powerful ‘last-line’ class of antibiotics.[3] The NDM-1 gene has since been identified in over 16 countries and has spread to 14 different species of bacteria, including pathogenic varieties responsible for dysentery and cholera.[4]
Suggestions of a post-antibiotic apocalypse are clearly more than mere hyperbole. Already, resistant bacterial infections kill around 25,000 people annually in Europe,[5] and resistance to antibiotics costs the US between $17 billion and $26 billion a year.[6] Despite the human and financial toll, and a robust understanding of the spread of antimicrobial resistance, satisfactorily addressing this phenomenon has remained elusive. Outside healthcare, relatively little attention has been given to the issue, especially among legislators and policy makers. Some experts suggest an analogy with climate change. According to Professor John Conly, Chairman of the Board for the Canadian Committee on Antibiotic Resistance, “The problem is that [antimicrobial resistance] is somewhat akin to climate change and so slow and insidious that people, and notably our politicians, are lulled asleep.” Many governments around the world haven’t yet grasped the gravity of the situation.
Staying ahead of the microbes will require combined action by many different stakeholders including policy makers, regulators and drug companies, not just by healthcare providers and patients. Worryingly, the drug development pipeline for new antimicrobials is slim. Between 1983 and 1887, 16 new antibiotics received approval by the FDA, yet from 2003 to 2011, just seven have done so.[7] This state of affairs probably reflects the relatively unattractive financial incentives for the development of new antimicrobials. Drug-resistant infections are still a small proportion of the total number of infections, so the market for new antibiotics is small. Furthermore, much of the resistance is in countries that cannot afford expensive new drugs. Finally, successful treatment generally involves taking the drugs over a short period rather than for life – good for the patient but less so for the manufacturer.
In the hope of encouraging the development of new antimicrobials, the Infectious Diseases Society of America has put forward its “10×20” plan, which calls for the development of ten new antibiotics by 2020. It has proposed financial incentives such as tax credits, guaranteed markets and extended patent protection, to encourage investment in research and development.[8]
In the battle against antimicrobial resistance, we cannot afford to procrastinate. Concerted urgent global efforts are needed to avoid regressing to the pre-antibiotic era. Whether or not we will succeed in the war against antimicrobials is far from certain. The Director of the Antibiotic Resistance Monitoring and Reference Laboratory of the UK Health Protection Agency, Dr Livermore, does not appear optimistic: “The emergence of antibiotic resistance is the most eloquent example of Darwin’s principle of evolution that there ever was. It is a war of attrition. It is naïve to think we can win.”
References
[1] Hughes J.M. Preserving the lifesaving power of antimicrobial agents. JAMA 2011; 305:1027-1028.
[2] FDA Reports to Slaughter: Over 70 Percent of Antibiotics Administered to Animals In Feed. Retrieved 02/05/2012 from www.louise.house.gov/index.php?option=com_content&view=article&id=2481:fda-reports-to-slaughter-over-70-percent-of-antibiotics-administered-to-animals-in-feed-&catid=95:2011-press-releases&Itemid=55 12.
[3] Kumarasamy K.K., Toleman M.A., Walsh T.R. et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 2010; 10:597-602.
[4] Nordmann P., Poirel L., Walsh T.R., Livermore D.M. The emerging NDM carbapenemases. Trends Microbiol 2011; 19:588-595.
[5] World Health Organization. Antimicrobial Resistance: Information for Policy Makers. Fact Sheet. 2012. Retrieved 02/05/2012 from www.euro.who.int/en/what-we-do/health-topics/disease-prevention/antimicrobial-resistance/antibiotic-resistance/factsheets/information-for-policy-makers
[6] Roberts R.R., Hota B., Ahmad I. et al. Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship. Clin Infect Dis 2009; 49:1175-1184.
[7] Infectious Diseases Society of America. Antimicrobial Resistance. 2012. Retrieved 02/05/2012 from www.idsociety.org/AR_Policy
[8] Infectious Diseases Society of America The 10 x ’20 Initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin Infect Dis 2010; 50:1081-1083.