Researchers have discovered that whole genome sequencing can impact infection control and patient management because of the clinical relevant data that it provides on bacterial transmission. In collaboration with Illumina researchers, scientists from Cambridge University's Wellcome Trust Sanger Institute have used whole genome sequencing to establish which isolates of methicillin-resistant Staphylococcus aureus (MRSA) were part of a hospital outbreak, since current lab techniques are often unable to distinguish between MRSA isolates.

The new study, published in New England Journal of Medicine, has demonstrated that whole genome sequencing cannot only rapidly supply accurate data, it also clearly distinguish between MRSA isolates.

MRSA infection is a leading public health problem. 2008 U.S. estimates show that 15,249 deaths were attributed to 89,785 invasive MRSA infections. On average, patients with MRSA infections spend twice as long in hospital compared to other patients who came in for the same reasons. Longer hospital stays, plus the treatments to deal with these type of infections raise the cost of health care.

In order to better control healthcare-associated infection, it is crucial to rapidly and accurately identify bacterial transmission.

Leading researcher, Professor Sharon Peacock, from Cambridge University explains:

"An important limitation of current infection control methodology is that the available bacterial typing methods cannot distinguish between different strains of MRSA. The purpose of our study was to see if whole genome sequencing of MRSA could be used to distinguish between related strains at a genome level, and if this would inform and guide outbreak investigations."

The researchers based their study on an MRSA outbreak in a neonatal intensive care unit that had already terminated, obtaining samples and sequencing them in real-time. They discovered that whole genome sequencing enabled them to distinguish between strains that were part of the outbreak and those that were not. This demonstrated that the outbreak could have been identified more rapidly compared with current clinical testing, and therefore potentially reducing the size of the outbreak.

Co-leading researcher, Dr Geoffrey Smith, Senior Director of Research at Illumina declared:

"This study demonstrates how advances in whole genome sequencing can provide essential information to help combat hospital outbreaks in clinically relevant turnaround times. As sequencing has become increasingly accurate and comprehensive, it can be used to answer a wide range of questions. Not only could we distinguish different MRSA strains in the hospital, we were also able to rapidly characterize antibiotic resistance and toxin genes present in the clinical isolates."

The team subsequently developed a list of all the MRSA genes that cause antibiotic resistance to allow a rapid identification of drug resistance in MRSA strains, which will assist healthcare professionals in treating each infected patient with the most appropriate therapy possible. Additionally, it provides a powerful tool to discover new drug resistance mechanisms.

MRSA generates various unique toxins that can lead to severe clinical syndromes, such as septic shock, pneumonia, and complicated skin and soft tissue infections. The researchers developed a list of toxin genes to rapidly identify these genes that occur in the MRSA strains. At present, these toxins can only be identified with multiple assays in reference laboratories.

Leading author, Dr Julian Parkhill from the Wellcome Trust Sanger Institute remarked:

"Distinguishing between strains is important for infection control management. Quick action is essential to control a suspected outbreak, but it is of equal importance to identify unrelated strains to prevent unnecessary ward closures and other disruptive control measures. Healthcare need better, more efficient ways of identifying an outbreak and then processes the data. Current clinical methods to make links between related strains compare the pattern of bacterial susceptibility to a profile of antibiotics. We found this method to be inaccurate. We identified two MRSA strains, that seemed to be identical using current methods, were genetically very different."

Ultimately, using whole genome sequencing will become part of routine health care, and these findings have made a contribution to support whole genome sequencing in controlling MRSA and other outbreaks in hospital settings.

Professor Peacock concluded: "The next stage is to develop interactive tools that provide automated interpretation of genome sequence and provide clinically meaningful information to healthcare workers, a necessary advance before this can be rolled out into clinical practice."

Written by Petra Rattue