̽��ֱ�� of Cambridge - sequencing

Using genome sequencing to track MRSA in under-resourced hospitals

sc604 — Tue, 09 Dec 2014 18:00:00 +0000

Researchers from the ̽��ֱ�� of Cambridge have used genome sequencing to monitor how the spread of methicillin-resistant Staphylococcus aureus (MRSA) occurs in under-resourced hospitals. By pinpointing how and when MRSA was transmitted over a three-month period at a hospital in northeast Thailand, the researchers are hoping their results will support evidence-based policies around infection control.

MRSA is a common cause of hospital-acquired infections, with the largest burden of infections occurring in under-resourced hospitals in the developing world. Whereas genome sequencing has previously been applied in well-resourced clinical settings to track the spread of MRSA, how transmission occurs in resource-limited settings is unknown. In a new study published today (9 December) in the journal Genome Research, researchers used genome sequencing to understand the spread of MRSA in a hospital with high transmission rates.

“In under-resourced hospitals and clinics, formal screening procedures for MRSA are not in place,” said Professor Sharon Peacock of the ̽��ֱ�� of Cambridge and the Wellcome Trust Sanger Institute, who led the research. “Filling gaps in our understanding of how MRSA spreads in such settings is important, since this not only highlights the problem but also provides direction to interventions that tackle this and other hospital-based pathogens.”

̽��ֱ��team of researchers from the UK, Thailand and Australia monitored all patients on two intensive care units (ICUs) at a hospital in northeast Thailand over a three-month period in order to track how and when MRSA was transmitted. During this time, five staff members and 46 patients tested positive at least once, which represented 16% of adult and 34% of paediatric patients.

Conventional bacterial genotyping approaches do not provide enough discrimination between closely-related MRSA strains to be able to pinpoint transmission from one person to another, but whole genome sequencing addresses this problem. A total of 76 MRSA populations, or isolates, were sequenced, including up to two repeat isolates from patients who tested positive for MRSA in the first screen. None of the patients or staff members who tested positive for MRSA were asymptomatic carriers.

By conventional typing, all of the MRSA identified belonged to sequence type 239, the dominant MRSA lineage worldwide. But, based on sequence data, there was considerable genetic diversity – including the presence or absence of clinically important genes such as those coding for antiseptic resistance and antibiotic resistance.

“A striking result from sequence data was the presence of multiple distinct clades, which suggests that several different variants of MRSA were circulating through the hospital at the same time,” said Peacock. “We also confirmed numerous transmission events between patients after admission to the ICU, and identified a ‘super-spreader’ in each unit.”

“Studies such as this provide information to help inform policy,” said Peacock, who is a member of the Department of Medicine and the Department of Pathology, and a Fellow of St John’s College. “It also highlights – in a concrete way – the importance of infection control including effective implementation of hand-washing, which is the most effective way to control MRSA.”

Following the results of the study, the hospital has implemented a comprehensive hand-washing policy, a project which is being overseen by Ben Cooper, one of the paper’s co-authors.

̽��ֱ��research was funded by the Medical Research Council.

Whole genome sequencing of MRSA from a hospital in Asia has demonstrated patterns of transmission in a resource-limited setting, where formal screening procedures are not feasible.

This study highlights – in a concrete way – the importance of infection control including effective implementation of hand-washing, which is the most effective way to control MRSA

Sharon Peacock

NIAID

Micrograph of Methicillin-Resistant Staphylococcus aureus (MRSA)

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Stopping superbugs in their tracks

bjb42 — Mon, 01 Nov 2010 14:10:52 +0000

Hundreds of millions of patients around the world are affected by healthcare-associated infections each year, although the true scale of their global burden and impact on health remains unknown because of the difficulty in gathering reliable data. In developing countries, the problem of such infections is compounded by the fact that the pathogens involved are frequently resistant to the antibiotics available.

Reducing mortality and morbidity from healthcare-associated infections depends on effective prescribing policies based on information provided by diagnostic microbiology, as well as prevention through improved hygiene such as frequent hand washing. ‘One of the major difficulties in resource-poor countries,’ says Professor Sharon Peacock, from the Departments of Medicine and Pathology, ‘is the lack of even simple diagnostic microbiology in many hospitals. As a result, many pathogens go unrecognised.’

Having spent most of the past decade working in resource-restricted areas of south-east Asia, Professor Peacock believes that researchers can help tackle this problem using technology at two ends of the spectrum. ‘By supporting the development of low-cost, sustainable diagnostic microbiology laboratories to identify pathogens, information is generated to guide prescribing and highlight the need for infection control. This also provides bacterial strain collections that can then be examined using cutting-edge tools to define transmission pathways of important pathogens at local, national and global levels.’

Detective work

̽��ֱ��antibiotic-resistant MRSA ‘superbug’ has a deservedly high profile across the developed world but is barely on the radar in developing countries. For example, until recently, there had been no documented report of MRSA in Cambodia. This isn’t because the country has remained completely free of the pathogen but simply because there were no facilities to detect its presence. Now, the Angkor Hospital for Children in Western Cambodia has such a laboratory, the development of which was supported by a team led by Professor Peacock while working at the Wellcome Trust-Mahidol ̽��ֱ��-Oxford Tropical Medicine Research Unit in Thailand, where she continues to support research following her move to Cambridge in 2009.

Within a month of opening, the first child with MRSA infection was identified. And, with continued support from Cambridge- and Thailand-based researchers, the laboratory has recently reported that MRSA causes infection in both the hospital and the community, and is being carried by a proportion of the population.

̽��ֱ��impact of detecting these and other multi-resistant pathogens is potentially huge, explains Professor Peacock: ‘Such information alerts healthcarers and policy makers of the possibility of infection with these organisms and the risk of treatment failure using the readily available antimicrobial drugs, as well as supporting the need for hand washing to reduce spread among hospital patients’.

Tracking the global spread of multi-resistant pathogens

As highlighted by a study published this year in Science magazine, cutting-edge technology also has an important role to play. In this study, Professor Peacock was part of a team led by the Wellcome Trust Sanger Institute at Hinxton, Cambridge, which developed high-throughput genome sequencing to study the transmission of a single clone of MRSA that has become disseminated across much of the world.

Existing techniques were unable to discriminate between individual strains, but genome sequencing showed that no two strains were genetically identical. ̽��ֱ��beauty of the technique is that it allows healthcare officials to see how MRSA, or any other pathogen, can evolve and spread – from person to person, from hospital to hospital, and from country to country.

Professor Peacock’s research is continuing to use this sophisticated technology to inform better infection control of MRSA, and other pathogens, in hospital settings. ‘Being able to feed this information back to hospitals,’ she explains, ‘is key for interventions to be targeted with precision and according to need.’

For more information, please contact Professor Sharon Peacock (sjp97@cam.ac.uk) at the Departments of Medicine and Pathology. Professor Peacock chairs the Cambridge Infectious Disease Initiative, one aim of which is the development and translation of research in developing countries.

Work in resource-restricted healthcare settings in south-east Asia is defining the transmission of hospital ‘superbugs’ using low-tech diagnostics and high-tech tools.

One of the major difficulties in resource-poor countries is the lack of even simple diagnostic microbiology in many hospitals. As a result, many pathogens go unrecognised.

Professor Sharon Peacock

Matt Holden, WT Sanger Institute

MRSA

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Superbug detective

bjb42 — Sat, 01 May 2010 00:00:00 +0000

On returning to the UK after seven years in Thailand researching infectious diseases, Cambridge's new Professor of Clinical Microbiology, Sharon Peacock, has taken up with an 'old friend', as she resumes her long-standing research interest in the bacterium Staphylococcus aureus, particularly the MRSA strains that have become resistant to the antibiotic drug methicillin. ̽��ֱ��increasing incidence of antibiotic resistance in such bacteria is a global health threat. Her expertise is helping to drive a programme of research that will track and block routes of transmission for these 'superbugs'.

Based within the Departments of Medicine and Pathology, and working closely with the Health Protection Agency and the Wellcome Trust Sanger Institute, Professor Peacock has recently returned from the Mahidol-Oxford Tropical Medicine Research Unit in Thailand. There, she directed a wide-ranging programme of bacterial disease research focused on prevalent diseases in South-East Asia. This included clinical treatment trials, diagnostic test development and the molecular epidemiology of several bacteria.

Professor Peacock has also had a long-term interest in MRSA, which over the past four decades has spread around the world and is resistant to many of the antibiotics commonly used in hospitals. ‘Tracking how MRSA spreads can be likened to playing detective since it’s all about trying to identify and follow specific strains of bacteria as they move globally, between countries and between individuals,’ she explained. ‘It’s important that we can do this because measures can then be introduced to further reduce transmission in settings where the bacteria pose the greatest problem such as hospitals.’

Through a collaboration with the Wellcome Trust Sanger Institute, her research has already had a dramatic impact on moving forward the detective story: in 2004, the genome of the MRSA strain that is a common cause of hospital-based infection in the UK was sequenced; and in January 2010, a new method for tracking transmission routes based on the rapid sequencing of genetic differences between strains was published in Science. Her focus now is to translate these research tools from the laboratory into the clinical setting, so that preventive interventions can then be targeted with precision and according to need

What’s the best piece of advice you’ve ever been given?

‘Make it hard, but make it look easy’; in other words, challenge yourself, but don’t let on that it’s so difficult. I’ve always tried not to settle into a comfort zone for very long before I’m looking for the next challenge, and the one after that.

Have you ever had a Eureka moment?

Yes – when I realised that what I really wanted to be was a doctor. But, at the time, I was six months into student nurse training, and having left school at 16 almost empty handed and without the O-levels I needed to study medicine. It was only when I saw how enthralling the whole diagnostic process was – taking a history, examining the patient, carrying out investigations, and reaching a diagnosis – that I knew that’s what I wanted to do. I had a very long way to go to achieve it. I did my O-levels at night school, then my A-levels part-time while working as a nurse to fund myself. It was quite difficult to get into ̽��ֱ�� to study medicine because of this unusual background, but Southampton ̽��ֱ�� gave me the opportunity. I haven’t really had a Eureka moment since – I’ve just been trying to achieve what I set out to do all those years ago!

If you could wake up tomorrow with a new skill, what would it be?

Wouldn’t it be good to wake up and realise you could run a marathon? I’m a very keen spinner – it’s a fitness regimen using a specially designed stationary bike – and I’d love to have the fitness of a marathon runner.

What is your favourite research tool?

There’s no doubt that access to information on the scale the internet provides has revolutionised the way we do our work. It’s hard to imagine that, when I was a medical student, finding scientific articles involved a trip to the library and locating the right volume of Index Medicus on a bookshelf, all to provide what PubMed does at the touch of a button. ̽��ֱ��other major research tool for me is the advent of high-throughput sequencing technology, and the speed with which we can now sequence genomes and tell individual strains of bacterial pathogens apart, some of which may only differ at a few bases of DNA. It’s an incredibly powerful tool in the battle against the spread of bacteria.

What will the future look like in 2050?

Antibiotic resistance in bacteria is a result of the widespread use of antibiotics over recent decades. Unless we embark on a better global vision for conserving the efficacy of current drugs by limiting their use, this will be a major problem in the future. However, we’ll have a better genetic understanding of bacterial pathogens and based on this I hope that we’ll be able to identify weaknesses that can be targeted with a new generation of antibiotics. And, crucially, many of the technologies that are now becoming available for diagnosing and tracking disease will be translated into cost-effective clinical tools. Even in the face of rising antibiotic resistance, we’ll have the front-line measures to understand and reduce bacterial transmission and limit the spread of infection.

̽��ֱ��expertise of Cambridge's new Professor of Clinical Microbiology, Sharon Peacock, is helping to drive a programme of research that will track and block routes of transmission for superbugs.

Tracking how MRSA spreads can be likened to playing detective since it’s all about trying to identify and follow specific strains of bacteria as they move globally, between countries and between individuals."

Sharon Peacock

̽��ֱ�� of Cambridge

Sharon Peacock

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