Antibiotic resistance in agricultural environments: A call to action

Sep. 26, 2013 — Antibiotic resistant pathogens are an emerging, critical human health issue. The World Health Organization (WHO) has declared antibiotic resistance as a top health issue worldwide. Two million Americans are infected each year with diseases resistant to known antibiotics; between ten and fifteen thousand die.Jean McLain, PhD, will present “Antibiotic Resistance in Agricultural Environments: A Call to Action,” on Tuesday, Nov. 5, 2013 at 4:30 PM. The presentation is part of the American Society of Agronomy, Crop Science Society of America, and the Soil Science Society of America Annual Meetings, Nov. 3-7 in Tampa, Florida. The theme of this year’s conference is “Water, Food, Energy, & Innovation for a Sustainable World.”Most people equate antibiotic resistance to the medical field. However, antibiotic resistance is also in our soils. And, the field of agriculture has been blamed for making this worse by using concentrated feed operations that leak antibiotics into surrounding waterways. …

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Local animal populations contribution to human Salmonella infections overstated

Sep. 12, 2013 — A new study has shown that, contrary to popular belief, local domestic animals are unlikely to be the major source of antibiotic resistant Salmonella in humans. The result comes from a detailed study of DNA from more than 370 Salmonella samples collected over a 22-year period.By studying the genetic variation in the Salmonella bacteria and their drug resistance genes, researchers found that distinguishable bacterial populations exist in human and animal populations living side by side. Antibiotic resistance is considered to be one of the most important dangers to human health, threatening to make many treatments to common infections ineffective. By comparing the genomes of Salmonella in humans and animals the researchers have provided important new insights into the likely sources and spread of antibiotic resistant infections. First, the Salmonella bacteria largely remained within their original host populations and second, there were more varied combinations of drug resistance in the human-infecting bacteria.Salmonella infection is a global issue, with approximately 94 million people contracting gastroenteritis or food poisoning each year. The combined annual cost in the United States and European Union is estimated to be more than £4 billion ($6 billion). This public health issue is exacerbated further by antibiotic resistance, which can lead to more complicated and protracted illness in patients and increased treatment costs.”For the first time we’ve determined in detail and on a large scale how Salmonella strains taken from humans and animals in the same setting and over the same time period relate to each other,” says Dr Alison Mather, first author on the study, from the Wellcome Trust Sanger Institute. “Our genomic data reveal how the Salmonella bacteria spread during the course of a long-term epidemic. We found that people have a more diverse source of infection and antibiotic resistance than just the local animals, pointing towards alternative sources.”The team sequenced DNA from 373 samples from humans and animals infected with Salmonella Typhimurium DT104 over a 22-year period, mainly from Scotland, but also from other countries. …

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Scientists uncover how superbug fights off antibiotic

Aug. 28, 2013 — Investigators working to stem the spread of antibiotic-resistant bacteria have taken a major step in their efforts to develop new treatments.In mBio, researchers at The University of Texas Health Science Center at Houston (UTHealth) report they have identified a novel mechanism that a particular superbug uses to fend off a key front-line antibiotic called daptomycin. The superbug often affects critically ill patients.This information is helping investigators identify compounds to knock out a mechanism of resistance in order to “disarm” the superbug.Prior to the mass production of antibiotics, a cut or strep throat could lead to serious illness or even death. Antibiotics gave doctors the ability to treat bacterial infections. But, bacteria have developed mechanisms of resistance that can make antibiotics ineffective against the most aggressive superbugs.Thousands of people succumb to superbug-related infections worldwide annually and superbugs account for $20 billion in excess health care costs in the United States each year.”Antibiotic resistance is one of the major public health threats of the 21st Century,” said Cesar Arias, M.D., Ph.D., the study’s senior author and associate professor in the Division of Infectious Diseases at the UTHealth Medical School. “These superbugs can make antibiotics useless, which makes certain bacterial infections virtually untreatable.”While there are several types of antibiotic-resistant bacteria, the study focused on a hard-to-treat superbug called vancomycin-resistant enterococci or VRE. VRE usually affect patients who have a compromised immune system or who are critically ill.The frequency of VRE recovered from hospitalized patients in the United States has increased eightfold in the last 15 years, becoming the second most common hospital-associated bacterium in the United States, Arias said.The superbug appears to be building resistance to one of the few antibiotics that works against it — daptomycin.To see how VRE developed the ability to ward off daptomycin during the course of treatment, Arias’ team used fluorescent labeled daptomycin and observed the interaction between the superbug and the antibiotic with the aid of advanced microscopy techniques.Contrary to the prevailing belief that tiny electrical charges on the surface of VRE cells repel the antibiotic, the researchers report that the VRE cells actually divert the antibiotic and “trap” it to an area where it is rendered ineffective. The mechanism of resistance is completed by changing the composition of the bacterial cell membrane. The study also provides the genetic and biochemical basis for the resistance pathway.”The importance of this work is that an understanding of ‘how’ bacteria become resistant can then lead to a search for new antibiotics that target the resistance pathway itself, thus overcoming and preventing resistance,” said Barbara E. Murray, M.D., study co-author as well as director of the Division of Infectious Diseases and holder of the J. …

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Antibiotic reduction campaigns do not necessarily reduce resistance

July 29, 2013 — Antibiotic use — and misuse — is the main driver for selection of antibiotic resistant bacteria. This has led many countries to implement interventions designed to reduce overall antibiotic consumption. Now, using methicillin resistant Staphylococcus aureus (MRSA) as an example, Laura Temime of the Conservatoire National des Arts et Metiers, Paris, and collaborators warn that simply reducing antibiotics consumption does not necessarily reduce resistance.The research is published online ahead of print in Antimicrobial Agents and Chemotherapy.The success of antibiotic reduction programs depends on which antibiotics are reduced, because some select more strongly for resistance than others. For instance, in the case of S. aureus, reducing use of clindamycin and methicillin lead to decreased resistance, while reducing use of penicillins does not, since most S. aureus, including MRSA, are already resistant to penicillin, explains Temime.Additionally, efforts to reduce antibiotic use must be coordinated between hospitals and the community, since either can feed resistant bacteria into the other, undermining reduction efforts, says Temime.In 2002-2003, a national program reduced antibiotic use in France by 10 percent. However, it fell short of the full potential for reducing resistance because it failed to target those antibiotics that generate the most resistance, says Temime. She and her collaborators developed a mathematical model of MRSA circulation, which correctly simulated that reduction, post-facto. They then performed a number of simulations of reductions in antibiotic use, which demonstrated the complexities of reduction efforts.”We found that the reduction in MRSA hospital rates could have been much larger than it actually was following the 2002 antibiotic reduction campaign,” says Temime. “Our results also suggest that changes in the distribution of antibiotics prescribed for non-hospitalized patients actually limited the impact of the antibiotic reduction campaign in French hospitals.”Their research shows that class-specific changes in antibiotic use, rather than overall reductions, need to be considered in order to achieve the greatest benefit from antibiotic reduction campaigns, says Temime. …

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Do antibiotics in animal feed pose a serious risk to human health?

July 11, 2013 — As fears rise over antibiotic resistance, two experts on the British Medical Journal website today debate whether adding antibiotics to animal feed poses a serious risk to human health.David Wallinga from Keep Antibiotcs Working: the Campaign to End Antibiotic Overuse in Animal Agriculture, believes that physicians and policymakers have “overlooked the critical role played by the ongoing overuse of antibiotics in livestock and poultry.”He understands the interest in creating a pipeline of new antibiotics, but says overall reductions in antibiotic use “should come first.”He points to data showing that, in 2009-11, 72% of all US sales of antimicrobials comprised those routinely added to water or animal feed.These, he says, are “additives in feed given routinely, without a prescription, at lower than therapeutic concentrations, for purposes such as growth promotion and to control disease in otherwise healthy animals being raised in crowded or unhygienic conditions that promote disease.”Wallinga argues that, contrary to claims by some in the livestock and drug industries, “routine antibiotics are not necessary for animal health.” He points to Denmark, the world’s leading pork exporter, which reduced antimicrobial use in livestock production by 60% while increasing pork production by half since 1994.Based on a growing body of evidence, almost every European and North American public health authority agrees that routine antibiotic use in animal food production likely worsens the epidemic of resistance, he writes. “Less certain is the political will to act upon that information,” he concludes.But Veterinarian, David Burch, argues that medicated animal feed “poses no additional risk of resistance development than giving a human patient an oral antimicrobial.”He explains that some countries, such as the Netherlands, have banned routine use of antibiotics in animal feed, mainly over concerns about an increase in MRSA.But Burch argues that use of antibiotics in feed was not associated with an increase in MRSA because “no products which directly select for MRSA are registered for use in feed in the European Union.” It is mainly older antibiotics that are licensed for use in feed in the UK, he explains.He believes that how bacteria, which might carry resistant genes, are transmitted to humans must be considered, but says, given the thorough risk assessments concerning antimicrobial resistance by the regulatory authorities, “it is considered highly unlikely that the use of adding antibiotics to feed poses a serious risk to humans, especially in comparison with the extensive use of antibiotics directly in human patients.”

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Novel chemistry for new class of antibiotic

July 3, 2013 — University of Adelaide research has produced a potential new antibiotic which could help in the battle against bacterial resistance to antibiotics.The potential new antibiotic targets a bacterial enzyme critical to metabolic processes.The compound is a protein inhibitor which binds to the enzyme (called biotin protein ligase), stopping its action and interrupting the life cycle of the bacteria.”Existing antibiotics target the bacterial cell membranes but this potential new antibiotic operates in a completely different way,” says Professor Andrew Abell, project leader and Acting Head of the University’s School of Chemistry and Physics.Professor Abell says the compound, although at a very early stage of development — it has not yet been tested on an animal model — has the potential to become the first of a new class of antibiotics.”Bacteria quickly build resistance against the known classes of antibiotics and this is causing a significant global health problem,” he says. “Preliminary results show that this new class of compound may be effective against a wide range of bacterial diseases, including tuberculosis which has developed a strain resistant to all known antibiotics.”Developing the new protein inhibitor involved a novel approach called ‘in situ click chemistry’. A selection of small molecules, or ‘precursor fragments’, are presented to the bacteria in a way so that the target protein enzyme itself builds the inhibiting compound and also binds with it.”In a sense the bacteria unwittingly chooses a compound that will stop its growth and assembles it — like building a weapon and using it against itself,” says Professor Abell. “We’ve gone a step further to specifically engineer the enzyme so that it builds the best and most potent weapon.””Our results are promising. We’ve made the compounds; we know they bind and inhibit this enzyme and we’ve shown they stop the growth of a range of bacteria in the laboratory. The next critical step will be investigating their efficacy in an animal model.””Thanks to this new approach what might have taken a year or more with a range of sequential experiments, we can now do in one single experiment,” Professor Abell says.The research has been published in the journal Chemical Science and is in collaboration with researchers at Monash University and Adelaide’s Women’s and Children’s Hospital.

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