The Lancet Infectious Diseases Commission Antibiotic resistance—the need for global solutions Ramanan Laxminarayan, Adriano Duse, Chand Wattal, Anita K M Zaidi, Heiman F L Wertheim, Nithima Sumpradit, Erika Vlieghe, Gabriel Levy Hara, Ian M Gould, Herman Goossens, Christina Greko, Anthony D So, Maryam Bigdeli, Göran Tomson, Will Woodhouse, Eva Ombaka, Arturo Quizhpe Peralta, Farah Naz Qamar, Fatima Mir, Sam Kariuki, Zulfi qar A Bhutta, Anthony Coates, Richard Bergstrom, Gerard D Wright, Eric D Brown, Otto Cars The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences Published Online aff ect everybody in the world. Similarities with climate change are evident. Many eff orts have been made to describe the November 17, 2013 many diff erent facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated http://dx.doi.org/10.1016/ S1473-3099(13)70318-9 action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for See Online/Comments unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in http://dx.doi.org/10.1016/ modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, S1473-3099(13)70195-6, which we today take for granted, would not be possible without access to eff ective treatment for bacterial infections. http://dx.doi.org/10.1016/ Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and S1473-3099(13)70315-3, http://dx.doi.org/10.1016/ unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic S1473-3099(13)70317-7, resistance, its major causes and consequences, and identify key areas in which action is urgently needed. http://dx.doi.org/10.1016/ S1473-3099(13)70196-8, Part 1: Global epidemiology of antibiotic Resistance has spread worldwide. Antibiotic-resistant http://dx.doi.org/10.1016/ S1473-3099(13)70314-1, 5 resistance and use gonorrhoea emerged in Vietnam in 1967, then spread to the http://dx.doi.org/10.1016/ The rise of resistance Philippines, and fi nally the USA.6 NDM enzymes, fi rst S1473-3099(13)70316-5, and The decreasing eff ectiveness of antibiotics in treating reported in 2008, are now found worldwide.7 The distri- http://dx.doi.org/10.1016/ common infections has quickened in recent years, and bution of resistance genes, such as Entero bacteriaceae- S1473-3099(13)70299-8 with the arrival of untreatable strains of carbapenem- Center for Disease Dynamics, Economics and Policy, resistant Enterobacteriaceae, we are at the dawn of a Washington, DC, USA 1 Panel: Contributions to the Commission postantibiotic era. In high-income countries, continued (R Laxminarayan PhD); high rates of antibiotic use in hospitals, the community, The Commission is a single document, each group of authors Princeton University, Princeton and agriculture have contributed to selection pressure that take responsibility for the text and views expressed in their NJ, USA (R Laxminarayan); Public Health Foundation of 2 has sustained resistant strains, forcing a shift to more individual parts. India, New Delhi, India expensive and more broad-spectrum antibiotics. In low- Part 1: Global epidemiology of antibiotic resistance and use (R Laxminarayan); University of income and middle-income countries (LMICs), antibiotic (page 1) the Witwatersrand, use is increasing with rising incomes, high rates of Johannesburg, South Africa Ramanan Laxminarayan, Adriano Duse, Chand Wattal, (A Duse MD); Sir Gangaram hospitalisation, and high prevalence of hospital infections. Anita K M Zaidi Hospital, New Delhi, India Resistance arises as a consequence of mutations in (C Wattal MD); Department of Part 2: Getting out of the impasse (page 5) microbes and selection pressure from antibiotic use that Paediatrics and Child Health, Heiman F L Wertheim, Nithima Sumpradit, Erika Vlieghe, provides a competitive advantage for mutated strains. Division of Women and Child Gabriel Levy Hara, Ian M Gould Health, The Aga Khan Suboptimum antibiotic doses help stepwise selection of University Karachi, Sindh, resistance. Resistance genes are borne on chromosomal, Part 3: Minimising the time to eff ective treatment—rapid Pakistan (A K M Zaidi MD, and increasingly, on transmissible extrachromosomal diagnostic testing (page 9) F N Qamar MBBS, F Mir PhD, Herman Goossens Prof Z A Bhutta PhD); Nuffi eld elements. The resulting resistant clones—eg, meticillin- Department of Clinical resistant Staphylococcus aureus (MRSA) USA 300, Part 4: The interface between people and animals (page 12) Medicine, Centre for Tropical Escherichia coli ST131, and Klebsiella ST258) are dis- Christina Greko Diseases, University of Oxford, seminated rapidly worldwide. This spread is facilitated by Oxford, UK Part 5: The access and excess dilemma (page 15) (H F L Wertheim MD); Food and inter species gene transmission, poor sanitation and Anthony D So, Maryam Bigdeli, Göran Tomson, Will Woodhouse, Drug Administration, hygiene in communities and hospitals, and the increasing Eva Ombaka, Arturo Quizhpe Peralta International Health Policy frequency of global, travel, trade, and disease transmission. Program, Ministry of Public Part 6: Challenges of antibiotic resistance in weak health Health, Nonthaburi, Thailand systems (page 19) (N Sumpradit PhD); Institute of Resistance is spreading worldwide Farah Naz Qamar, Fatima Mir, Sam Kariuki, Zulfi qar A Bhutta Tropical Medicine, Antwerp, Even before penicillin was introduced, resistant strains of Belgium and University bacteria had been detected.3 The selection pressure caused Part 7: Improving the interface between academics and the Hospital, Antwerp, Belgium by the use of millions of tonnes of antibiotics over the past pharmaceutical industry (page 23) (E Vlieghe MD); Infectious Anthony Coates, Richard Bergstrom Diseases Unit, Hospital 75 years since antibiotics were introduced has made almost Carlos G Durand, Buenos Aires, all disease-causing bacteria resistant to antibiotics Part 8: Beyond antibiotics—alternative strategies for Argentina commonly used to treat them. The rapid evolution of prevention and treatment (page 27) (Prof G Levy Hara MD); bacterial resistance is clear in the case of β-lactamases class Gerard D Wright, Eric D Brown Aberdeen Royal Infi rmary, Aberdeen, UK of antibiotics. Nearly 1000 resistance-related β-lactamases Part 9: Call to action (page 31) (I M Gould MBChB); Laboratory that inactivate these antibiotics have been identifi ed, a ten- Otto Cars, with contributions from all groups of authors of Medical Microbiology, times increase since before 1990.4 VAXINFECTIO, University of www.thelancet.com/infection Published online November 17, 2013 http://dx.doi.org/10.1016/S1473-3099(13)70318-9 1 The Lancet Infectious Diseases Commission Antwerp, Antwerp, Belgium producing extended-spectrum β-lactamase (ESBL), NDM-1, presumed sepsis. Most worrying is the emergence of pan- (H Goossens PhD); Department and Klebsiella pneumoniae carbapenemase (KPC), indicates resistant untreatable carbapenem-resistant Entero- of Animal Health and the ease with which resistance can spread. Findings of a bacteriaceae and Acinetobacter spp infections associated Antimicrobial Strategies, 8 16 National Veterinary Institute, study done in New Delhi showed NDM-1-producing with high mortality in neonatal nurseries. Uppsala, Sweden (C Greko PhD); bacteria (including Shigella boydii and Vibrio cholera) in two In Pakistan, the emergence of pan-resistant bacterial Sanford School of Public Policy, (4%) of 50 drinking water samples and 51 (30%) of isolates such as Acinetobacter spp and carbapenem- Duke University, Durham, NC, 171 seepage samples suggesting the possibility of acquiring resistant entero bacteria as causes of health-care associated USA (Prof A D So MD, W Woodhouse); Alliance for resistance outside health-care facilities. sepsis in hospitals is rendering these infections un- Health Policy and Systems Quinolone antibiotics in particular are an example of treatable.16–18 50–60% of community-acquired Gram- Research, WHO, Geneva, misadventure. These drugs are synthetic and so do not negative pathogens such as E coli associated with urinary Switzerland (M Bigdeli MPH); Departments of Learning, arise in nature, yet 30 years after their widespread tract infections have become resistant to common oral 9 Informatics, Management, introduction resistance is epidemic. More specifi cally, antibiotics (eg, amoxicillin, cefi xime, and ciprofl oxacin), Ethics and Public Health whole genome studies suggest that quinolone resistance complicating outpatient management. Sciences, Karolinska Institutet, 10 was a crucial factor in the evolution of hospital MRSA. Between July 2010 and August 2011, 72% of 1294 viable K Stockholm, Sweden (Prof G Tomson MD); School of Such examples of antibiotic-driven evolution go a long way pneumoniae isolates from sentinel sites in South Africa had 19 Pharmacy, St John’s University to explaining present epidemics of resistant health-care- antibiograms suggestive of ESBL production. Com- of Tanzania, Dodoma, associated infections.11 pounding this problem is the emergence of several Tanzania(E Ombaka PhD); In health-care settings, the spread of a resistant clone carbapenemase-resistance mechanisms. NDM-1 was fi rst Faculty of Medical Sciences, 20 University of Cuenca, Cuenca,