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Antibiotic resistance has become one of the great challenges to human health in the 21st century with increasing numbers of isolates of many pathogenic bacteria being resistant to front line, therapeutic antibiotics. Recent evidence has suggested that antibiotic resistance can be selected by exposure to biocides, which are commonly used as disinfectants and preservatives.
Research at the University of Birmingham has shown the common mechanistic links between antibiotic and triclosan (a commonly used biocide) resistance. This research was used by the European Commission as evidence to support two reports published in 2009 and 2010 to inform opinions as to the safety of biocide use. These reports recommended specific new research avenues be funded and that possible selection of antibiotic resistance by biocides is a valid concern and were used as part of the evidence base in preparation of a new law which has come in to force across the European Union.
Biocide use and sales in Europe have been controlled by the Biocidal Products Directive since 1998. This legislation has been superseded by the EU Biocides Regulation (published May 2012, legally binding from September 2013). This new legislation now includes a requirement for new biocides to be demonstrated not to select resistance to themselves or antibiotics in target organisms before achieving registration; this addition was informed by University of Birmingham research. This will prevent biocides entering the environment that exert a selective pressure and favour the emergence of mutant bacteria with increased biocide and antibiotic resistance. Thus the research described has had an impact on policy debate and the introduction of new legislation.
Cardiff Researchers in 2009 discovered the new antibiotic resistance determinant NDM-1 and in 2010/11 characterised its rapid worldwide spread through Gram-negative bacteria (e.g. Escherichia coli and Vibrio cholerae). NDM-1 redefined how antibiotic resistance can spread locally and internationally and create new extensively-drug resistance (XDR) that severely limits therapeutic options. This discovery has resulted in: 1) new policies for the admission of overseas patients to hospitals in the UK, France, USA, Australia and China, 2) linkage between MDR transmission and poor sewerage treatment, 3) potable water treatment in Southern Asia 4) positioning papers for the World Health Assembly and 5) policy-changes by the World Health Organisation.
Research by Professor Laura Piddock at the University of Birmingham has shown that the use of fluoroquinolone antibiotics in veterinary medicine can select for antibiotic resistance in certain strains of bacteria which then present a potential risk to human health. Fluoroquinolone antibiotics are widely used in human medicine to treat bacterial infections. For those patients with chronic bacterial gastroenteritis and/or an invasive infection, fluoroquinolone antibiotics are the empiric treatment of choice by GPs; resistance to these agents represents a large public health risk. The outcomes of the research have been used by policy makers to define the human risks of food borne infection from antibiotic resistant strains and have led to the review and amendment of international policy on the use of antibiotics in food producing animals, in particular the World Health Organisation (published outside of the review period) and US Food and Drug Administration (FDA). The research described has had a direct impact on international policy and the ban on the use of certain antibiotics has had an impact on the levels of fluoroquinolone resistance in bacteria isolated from food producing animals, reducing the transmission of resistant strains to humans.
From 1993 to 2005, Professor Errington and his colleagues at the University of Oxford addressed the increasingly serious global emergency of treating antibiotic-resistant bacteria. Their research led to the establishment in 1998 of the university spin-out company Prolysis Ltd and the discovery and development of two innovative series of antibiotics. The success of Prolysis Ltd was confirmed in 2009 when it was acquired by Biota Europe for £6.4 million, and gained an additional investment of £14.9 million. The subsequently formed Biota Pharmaceuticals Inc. continues to support the development of innovative broad-spectrum antibiotics essential to combat antibiotic-resistant bacteria.
Novel bioluminescent bacterial biosensors developed at UWE, Bristol, and commercialised by Randox, have been used by a range of companies to demonstrate effectiveness of drugs and decontamination procedures. This has improved development processes at companies including Clavis Pharma, Purest Solutions and Dycem, leading to new manufacturing processes and quality control test methods. The biosensors are used in novel applications to give pharmacodynamic data on effectiveness of drugs and real time in-situ demonstration of effectiveness of decontamination processes. These biosensors, pioneered and developed by Vyv Salisbury's group, have been commercially adopted and used for evaluation by at least six collaborating companies.
The need to measure and improve hospital antibiotic prescribing was identified as a priority in European and UK policy documents about antibiotic resistance in the late 1990s. Our research developed sustainable methods for evaluating interventions to improve hospital antibiotic prescribing, and led to Davey collaborating with the European Surveillance of Antimicrobial Consumption (ESAC) project and becoming the Scottish Antimicrobial Prescribing Group's Representative with Responsibility for International Liaison and Research. Implementation of ESAC quality indicators and measurement methods has been associated with progressive improvement in antibiotic policy compliance and reduction in Clostridium difficile infection in all 14 Health Boards in Scotland since 2008.
Genetic, biochemical and structural characterisation of drug targets in the human pathogen Streptococcus pneumoniae by Fisher and colleagues at St George's showed that antibacterial quinolones selectively target the enzymes gyrase, topoisomerase IV, or both, and led to the concept that `dual targeting' drugs minimise the emergence of drug resistance. They demonstrated the potency and the mechanism of action of besifloxacin, a fluoroquinolone developed by Bausch and Lomb which was subsequently approved by the FDA in 2009 for treatment of bacterial conjunctivitis. This has been shown to be a highly efficacious treatment with correspondingly increased usage and sales in the USA.
Research by the University of Southampton has contributed significantly to reducing the global threat of antibiotic resistance. A series of both conventional placebo-controlled and novel open design trials has influenced a number of important national clinical guidelines for Respiratory Tract Infections (RTIs) and the implementation of novel prescribing strategies that discourage unnecessary antibiotic prescription. As a direct result of the research, delayed prescribing for all acute respiratory infections is a tool in the everyday practice of the UK's GPs. Southampton's work in this field has informed international guidelines currently in place in the United States, Israel and the European Union.
Research led by Dr Holmes has identified a novel variant of methicillin-resistant Staphylococcus aureus (MRSA) in livestock. This represents a previously unidentified reservoir of infection which has had impact on the epidemiology of MRSA and its management. This research also impacts on antibiotic use in agriculture and its role in the emergence of antibiotic resistance. As a consequence of these research findings commercial tests and testing protocols have been developed to detect the new MRSA variant, which are now used widely in clinical settings throughout Europe. The discovery has also been used to inform policy decisions at a governmental level in the USA and Europe.
The use of implantable polymeric devices is limited by infection. University of Nottingham research led to patented technology for hydrocephalus shunts that provides biomaterials with long-acting antimicrobial action. Almost 70% of shunts used annually in England now comprise our [text removed for publication] shunt, and UK usage has grown by 22% since 2008. The technology has reduced infection rates from 8.75% (2008) to 3.6% (2013), and prevents around 370 brain infections and 38 deaths in England each year. This is saving NHS England an estimated £18.4m in treatment costs each year, and generating company revenue. Furthermore, our [text removed for publication] EVD catheters for temporary relief of intracranial hypertension have reduced the rate of brain infections from 7.6% to 0.9%.