The endless struggle
Authors: None The Lancet Infectious Diseases
Journal: The Lancet Infectious Diseases (2011)

Almost 10 years ago, in an editorial in this journal advocating the prudent use of antibiotics to limit development of resistance, we described these drugs as a “gift to be used sparingly”. In 2001, antibiotic resistance was not very fashionable beyond clinicians and researchers with first-hand knowledge of the topic. However, now that it is the focus of WHO's World Health Day on April 7, resistance has joined the front rank of global health concerns. What has brought antibiotic resistance into the limelight, and can this new-found status be harnessed to “safeguard these medicines for future generations”, to use the words of the World Health Day website? In 2001, WHO launched its Global Strategy for Containment of Antimicrobial Resistance. This report was, arguably, strong on recommendations but not on implementation. Besides, its impact was completely overshadowed by the events September 11, 2001, and subsequent posting of anthrax spores through the US mail, which shifted attention onto the threat of bioterrorism. Campaigning groups such as The Alliance for the Prudent Use of Antibiotics (APUA) and ReAct helped maintain the impetus to combat antibiotic resistance. The 2004 Infectious Diseases Society of America report Bad Bugs, No Drugs was important in bringing antibiotic resistance back to the attention of policy makers. But emerging epidemics of antibiotic-resistant infections are probably what has brought the issue into the public domain and thus piqued the interest of governments. A subject that might once have seemed rather distant from the man or woman in the street now frequently makes headlines. At times during the past decade, the casual observer could have been forgiven for thinking that hospitals in some countries were on the point of collapse from a wave of meticillin-resistant Staphylococcus aureus (MRSA) infections. And MRSA has now escaped into community settings, particularly in the USA. Clostridium difficile, the emergence of which as a serious health-care-associated infection is due to overuse of broad-spectrum antibiotics, shows increasing signs of resistance to several antibiotics, and has enjoyed a rise to public attention similar to that of MRSA. β-lactam resistance among Gram-negative bacteria is hardly a recent concern, but a carbapenemase-producing form called NDM-1, which also confers resistance to almost all antibiotics, grabbed attention worldwide last August when clusters of cases were reported from the Indian subcontinent and UK. Human infections with bacteria carrying the NDM-1 enzyme have now been reported from at least 20 countries. Let us also not forget the 440 000 or so cases of multidrug-resistant tuberculosis that occur worldwide every year. Indeed, a troubling feature of recent years is the increasing frequency of multidrug resistance among common bacteria, with around 400 000 Europeans having such infections annually. Our very rough estimate is that resistant infections double mortality, cost of treatment, and length of hospital stay. Bearing in mind that our objective is to contain antibiotic resistance rather than eradicate it, several policies could be adopted to help guarantee a future for antibiotics. We need reliable data to tackle antibiotic resistance. Thus establishment of a worldwide network of resistance-surveillance laboratories is essential, and a policy that WHO seems suited to implement. Prescribers relied on a stream of new antibiotics to treat infections with resistant organisms. Yet that stream reduced to a trickle by the end of the past century. There are signs of hope—by some estimates around 70 new antibacterials are undergoing clinical development, but few of these represent new classes of drugs or are active against Gram-negative infections. Market forces alone will likely not reinvigorate the antibiotic pipeline. Various ways have been suggested of incentivising the pharmaceutical industry including patent pooling, advanced market commitments, and prize funds. In the end, governments and other major global health donors may have to take a more active role in building on the model of public–private partnerships for development of drugs for neglected diseases. Ensuring that antibiotics are used only when indicated and not—for example—sold without prescription is essential. It is encouraging then that India and China, the world's two most populous nations, are preparing to announce new antibiotic policies and regulations. At the end of 2009 the presidents of the USA and EU agreed to establish a taskforce on antibiotic resistance, due to report this year. The interest of world leaders indicates that resistance is no longer being sidelined as a vital health issue. Although this interest is not itself sufficient to combat resistance, the post-antibiotic era is not yet upon us. A gift to be used sparingly3 years ago, representatives from the European Union met in Copenhagen, Denmark, to draw up a programme to combat the growing threat of antimicrobial-resistant pathogens. One of the main recommendations coming out of this meeting was that member nations should encourage the prudent use of antimicrobials and thus reduce the selective pressure that is causing resistant strains to emerge. Copenhagen recommendations are available in full at www.microbial.threat.dk ). This year the group reconvened in Visby, Sweden, to assess what progress has been made. Full-Text PDF Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological studyThe potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed. Full-Text PDF Open AccessPush and pull of antibiotic developmentLast month's summit between the European Union (EU) and the USA, in Washington, DC, saw US President Barack Obama and Swedish Prime Minister Fredrik Reinfeldt—on behalf of the EU Presidency—agree to establish a transatlantic taskforce to tackle antibiotic resistance. The Infectious Disease Society of America (IDSA) subsequently wrote to the respective leaders commending them on their undertaking and advising that the prospective taskforce include an antibacterial drug pipeline work group. The letter called for global commitment to the development of new antibacterial drugs. Full-Text PDF