HINXTON, UK—Although the toll from hospital-acquired infections in the UK has declined in recent years from a high of close to 10,000 deaths in 2007 to around half that number today, the recurrent outbreaks are still troubling enough to merit alarm bells around the world. Part of the problem faced by hospitals is that current diagnostic methods have not kept pace with the need for rapid public health interventions, such as moving patients to isolation wards or emptying and deep-cleaning contaminated wards. To help bring clinical management up to speed, a new British consortium has embarked on an ambitious project to translate advances in gene sequencing technologies into diagnostic tools for tracking the spread of infections and informing doctors how to contain outbreaks in near to real time.

The Modernising Medical Microbiology Consortium, a five-year £5.6 million ($8.7 million) effort funded by the UK Clinical Research Collaboration, is focused on four major pathogens: Staphylococcus aureus (including methicillin-resistant (MRSA) strains), Clostridium difficile, norovirus and the tuberculosis bacterium. The researchers involved in the project—who hail from the UK Health Protection Agency, the University of Oxford and the Wellcome Trust Sanger Institute—envision a day when DNA from a sick person can be sequenced and compared with samples in a database to determine whether he or she brought the infection into the hospital or acquired it on the ward, possibly because of poor staff hygiene.

The initiative's first published success came earlier this year when a team led by Oxford microbiologist Kate Dingle created a Web-accessible database of C. difficile strains based on sequencing a series of housekeeping genes, and showed that DNA can be extracted directly from stools within days without an intermediate culturing step (J. Clin. Microbiol. 48, 770–778, 2010).

Building on this research, Oxford's Rosalind Harding reported here at the Infectious Disease Genomics and Global Health conference that sequencing whole C. difficile genomes could reveal the pattern and timing of a particular strain as it spread within a hospital ward. As validation of this approach, the genome-based reconstruction of transmission patterns also gelled with independent epidemiological data showing that the people with direct transmissions had crossed paths on the hospital ward. “This is like on the scale of criminal forensics,” says Harding.

At the same meeting, Rory Bowden, a mathematical geneticist at Oxford, presented whole S. aureus genome data for more than 150 strains taken from two hospitals at two different time points each. Of note, the genomic data revealed a common ancestry among MRSA strains from a recent outbreak at the Brighton and Sussex University Hospitals NHS Trust, which had the worst MRSA infection rate in the country in 2006. This indicates that a particularly nasty form of MRSA must have swept through the wards, Bowden notes. So, despite the hospital's efforts to stay sterile by, among other measures, banning doctors from wearing neckties, the genomic data suggest that “it's perhaps less likely that the outbreak arose because of bad hygiene and more likely that it's just bad luck,” he says.

Although these genomic approaches currently show promise for historical data, Ryan Tewhey from the Scripps Research Institute in La Jolla, California says “there are still huge time lags before this will have clinical utility” in real time. Tewhey, who presented the genomes of 36 isolates of community-acquired MRSA at the meeting, notes that even though bacterial genomes can currently be sequenced for $100, he estimates that we are still five to ten years away from getting these genomes sequenced and assembled in a matter of days instead of weeks.

Even though the hardware is not yet in place to sequence deadly microbes on the spot in hospital settings, scientists should work now to refine the computational tools that instantly analyze such DNA tests, says Tanya Golubchik, an Oxford bioinformaticist who is part of the initiative. “We want to be there when it happens,” she says.