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Silley P.,MB Consult Ltd | Silley P.,University of Bradford
OIE Revue Scientifique et Technique | Year: 2012

The Clinical and Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility Testing can be considered the major international contributors to antimicrobial susceptibility testing. In this review, the author considers the differences between the respective organisations, examines the terminology used in antimicrobial susceptibility testing and argues for an urgent need to harmonise these definitions. While this may seem somewhat surprising, the terminology used to define resistance does differ. In this context, attention is given to the trend for 'resistance' to be defined by the epidemiological cut-off value, ratherthan by the long-established clinical breakpoint. The author goes on to discuss susceptibility testing methodologies and present an approach to setting clinical breakpoints.

Silley P.,MB Consult Ltd | Silley P.,University of Bradford | De Jong A.,Bayer AG | Simjee S.,Elanco Animal Health | Thomas V.,Intervet Innovation GmbH
International Journal of Antimicrobial Agents | Year: 2011

Antimicrobial surveillance systems in Denmark (DANMAP), The Netherlands (MARAN), Spain (VAV) and Sweden (SVARM) as well as the European Antimicrobial Susceptibility Surveillance in Animals (EASSA) were reviewed. Data have been considered for extended-spectrum cephalosporins, fluoroquinolones and macrolides against food-borne and commensal bacteria. The greatest challenge arises from the lack of agreement between programmes on what is meant by resistance through the use of different interpretive criteria. Indeed, it is shown here that the extent of the differences depends on the antibacterial compound being investigated, the methodology and the interpretive criteria used. This emphasises a need to agree a definition for resistance and for epidemiological cut-off values and to consider harmonising the antimicrobials used in surveillance. This analysis of the data highlights the usefulness of using both epidemiological cut-off values and clinical resistance breakpoints for the purpose of detection of decreased susceptibility and development of clinical resistance, respectively. It is concluded that harmonisation in resistance monitoring programmes is needed since there is potential for data to be appropriately used within risk analysis, providing the opportunity to implement appropriate risk management steps as a response to the public health issues arising from changes in antibiotic resistance in food-borne pathogens and commensal organisms. © 2011 Elsevier B.V. and the International Society of Chemotherapy.

Martinez M.,U.S. Food and Drug Administration | Silley P.,MB Consult Ltd
Handbook of Experimental Pharmacology | Year: 2010

This chapter provides an overview of our current understanding of the mechanisms associated with the development of antimicrobial drug resistance, international differences in definitions of resistance, ongoing efforts to track shifts in drug susceptibility, and factors that can influence the selection of therapeutic intervention. The latter presents a matrix of complex variables that includes the mechanism of drug action, the pharmacokinetics (PK) of the antimicrobial agent in the targeted patient population, the pharmacodynamics (PD) of the bacterial response to the antimicrobial agent, the PK/PD relationship that will influence dose selection, and the integrity of the host immune system. Finally, the differences between bacterial tolerance and bacterial resistance are considered, and the potential for non-traditional anti-infective therapies is discussed. © 2010 Springer-Verlag Berlin Heidelberg.

Pruden A.,Virginia Polytechnic Institute and State University | Joakim Larsson D.G.,Gothenburg University | Amezquita A.,Unilever | Collignon P.,Australian National University | And 10 more authors.
Environmental Health Perspectives | Year: 2013

Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action.

Silley P.,MB Consult Ltd | Silley P.,University of Bradford
Food Security | Year: 2013

Antimicrobials are used in the food chain. It is often not appreciated that the requirements for a sponsor of a veterinary antimicrobial drug intended for use in food-producing animals are more onerous than those for companion animals or indeed for man. This is primarily because of the issue of potential drug residues being ingested in the human diet. Indeed this is the rationale behind the Harmonised VICH Guideline 36. It is argued that this current trilateral (EU-Japan-USA) scientific guidance is appropriate to determine the safety of antimicrobial residues in the food chain; much of this thinking has been developed from previous considerations of these matters. In this contribution we will discuss this approach, which addresses the complexity of the human intestinal flora and reduces uncertainty when determining microbiological acceptable daily intakes, and make some concluding remarks with respect to food safety and security with respect to the use of antimicrobials. A variety of toxicological evaluations are performed to establish the safety of veterinary drug residues in human food and as part of such evaluation for veterinary antimicrobial drugs is the safety of their residues on the human intestinal flora; this is an important step in ensuring the safety of the food supply. © 2013 Springer Science+Business Media Dordrecht and International Society for Plant Pathology.

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