August 23, 2012

ADEADLY OUTBREAK of antibiotic-resistant bacteria last year at the Clinical Research Center of the National Institutes of Health offers a fascinating and frightening window on the future of medicine. Fascinating because scientists used whole-genome sequencing to obtain a fine-grained blueprint of the genetic material in the bacteria and to track how it spread. Frightening because the bacteria, resistant to multiple antibiotics, defied efforts to control it in the 234-bed hospital in Bethesda.

On June 13, 2011, a 43-year-old patient was transferred into the intensive-care unit. She was known to be carrying a resistant strain of the bacteria Klebsiella pneumoniae, probably from an earlier hospital stay. Such infections can be dangerous, with mortality rates upward of 50 percent. She was lucky — she recovered and was discharged July 15. Then, on Aug. 5, another case involving the bug was discovered from a different patient, who had never been in the same ward as the first. In the following weeks, an average of one new case was found each week in the hospital. By Jan. 1, there had been 17. Eleven patients died; six deaths were directly attributable to the bacteria.

To find out what happened, researchers from the National Human Genome Research Institute used sophisticated procedures to sequence, or blueprint, the whole genome of the superbug, starting with a sample taken from the first patient. The sequence provided data down to the level of nucleotides, the basic chemical building block of nucleic acids. DNA and RNA are made up of long chains of nucleotides. The genome of the bacteria was then compared with other samples from other patients, allowing researchers to map how the bug had skittered around the hospital. It was discovered that Patient No. 1 may have transmitted the superbug three different times.

The sleuthing, described in a report in the journal Science Translational Medicine, is an example of how remarkable advances in genomics are changing our understanding of the biology of disease and medical conditions. With fast results and lower costs, genomics are being applied to real-world problems; in this case, how to control a dangerous infection outbreak in a hospital. The promise of genomics has been slow in realization, but it is becoming a reality.

The outbreak also calls attention to the deepening problem known as antimicrobial resistance, particularly in hospitals. As bacteria evolve, they develop resistance to antibiotics. In this case, the germ was highly resistant to multiple drugs, leaving doctors with no effective therapeutic options for some people. The superbug was tenacious, surviving in sink drains and on a ventilator that had been thoroughly cleaned.

The rise of antimicrobial resistance is a public-health crisis. Many first-line antibiotics are losing their efficacy, and the pipeline of new compounds is drying up. Pharmaceutical companies are leaving the market, unwilling to make the sizable investments in research and development required for new drugs. The story of the outbreak at the NIH is a strong reminder of the need for judicious use of existing antibiotics and for a fresh drive to create and win regulatory approval of effective new drugs.