Antimicrobial Resistance (AMR)

by

David Patrick, Rachel McKay, Patricia Keen

• LAST REVIEWED: 23 August 2017
• LAST MODIFIED: 23 August 2017
• DOI: 10.1093/obo/9780199756797-0167

Introduction

Among the public health risks of the 21st century, treatment failure from antibiotic resistance in human pathogens now ranks highly. As more evidence is gathered to better understand the development of antibiotic resistance of microbes at the organism, molecular, and genetic levels, the need for society to address this health risk has become more urgent. Within a few years following Alexander Fleming’s discovery of penicillin in 1928 as the first antibiotic widely deployed for clinical use to treat infections (Fleming 1929), the appearance of penicillin resistant organisms demonstrated that human ingenuity could not totally triumph over nature. Over the course of the decades that followed, with each new antibiotic drug that was introduced for medical therapy, antibiotic resistance emerged in various species of bacteria shortly thereafter. Resistance is now apparent in many domains of the biosphere. Currently, community-level, national, and international recognition of consequences of treatment failure of critical infectious diseases together with increased public awareness has fueled concentrated efforts to address this important human health risk. Coordinated global action is gaining momentum, but there remain many gaps. This bibliography provides an overview of the evolutionary basis of the problem and outlines the key elements of response: surveillance, stewardship of antibiotics, infection prevention and control, and innovation of new antibiotics, alternatives, and preventive strategies.

General Overviews

For more than fifty years, a number of naturally derived and synthetic antibiotic drugs have been developed to treat pathogenic infections (Fleming 1929). These drugs are categorized in different classes based on their mode of action. Because many drugs of these antibiotic classes are used in medical treatment of both humans and domestic animals, there is ongoing debate about the degree to which antibiotic use in veterinary medicine influences the risk of treatment failure due to development of antimicrobial resistance in human patients (Forsberg, et al. 2012). As consumer demand for affordable protein sources increased, farming practices shifted toward high-density food animal production facilities that fundamentally changed veterinary treatment strategies for herds or flocks. Antibiotic compounds have been used in the production of food animals to treat disease outbreaks, to prevent disease in dense populations, and often simply to promote their growth. Awareness that prudent use of antibiotics in veterinary medicine is critically important in minimizing the health risks associated with development of antimicrobial resistance in human pathogens is growing (Roca, et al. 2015). International trade of food products and human travel throughout all regions of the world have important implications for the transmission of infectious diseases. Since the late 1990s, pharmaceutical companies no longer invest in the development of new antibiotic drugs to any great extent and as a result there are few treatment options for bacterial infections that are highly resistant to most classes of antibiotics.

• Fleming A. 1929. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzæ. British Journal of Experimental Pathology 10.31: 226–236.

  This is the first report about the derivation of penicillin G from the specific mold and the description of the antibiotic properties of the compound. This original research led Alexander Fleming to be awarded the 1945 Nobel Prize in Physiology or Medicine together with Howard Florey and Ernst Boris Chain.

• Forsberg, K. J., A. Reyes, B. Wang, E. M. Selleck, M. O. Sommer, and G. Dantas. 2012. The shared antibiotic resistome of soil bacteria and human pathogens. Science 337:1107–1111.

  DOI: 10.1126/science.1220761

  Soil dwelling bacteria have adapted to survive in their habitats by developing genetic mechanisms including those that provide resistance to antibiotics. Soil ecosystems are considered reservoirs for antibiotic resistance and for some time, there has been concern that exchange of genetic determinants of resistance between environmental bacteria and clinically important pathogens can occur. This work provides evidence that lateral exchange of antibiotic resistance genes does occur and it also describes one mechanism through which antibiotic resistance is spread.

• Roca, I., M. Akova, F. Baquero, et al. 2015. The global threat of antimicrobial resistance: Science for intervention. New Microbes New Infections 6:22–29.

  DOI: 10.1016/j.nmni.2015.02.007

  This article presents a summary of a recent meeting to explore the current situation of antimicrobial resistance in animals and the food chain, within the community, and the healthcare setting. It also describes the role of the environment and the development of novel diagnostic and therapeutic strategies, providing expert recommendations to tackle the global health risk of antimicrobial resistance.