Friday, August 24, 2012

XX Tech Report: Rapid detection and treatment for deadly blood infections

Methicillin-resistant Staphylococcus aureus (green), a frequent agent
in blood infections, under attack from a white blood cell.
Photo: Wikimedia Commons, public domain.

By Jeffrey Perkel, Ph.D., DXS technology editor

[Ed. note: Introducing our new technology editor, Jeffrey PerkelJeffrey, a recovering scientist, has always had a passion for the technology and the gadgetry of science. He has been a scientific writer and editor since 2000, when he left academia to join the staff of The Scientist magazine as a Senior Editor for Technology. Before that, he studied transcription factor biology at the University of Pennsylvania and Harvard Medical School -- training that, surprisingly, has little application in the real world. In 2006, he and his family headed west to Pocatello, Idaho, and has been a freelance writer ever since. You can see why Double X Science is thrilled to have him on the team! You can find Jeffrey at his Website or on Twitter at @j_perkel. Welcome, Jeff!]

A story published earlier this week on NBCNews.com both alarmed me and piqued my interest.

It alarmed me because, well, I don’t like microbes much (despite, or perhaps because of my background in microbiology), and this article is about people getting very, very sick from sepsis (aka septicemia or bacteremia, an infection of the blood), which presents itself as a whole-body inflammatory response and a significantly increased risk of organ failure. It is an important area of microbiology because sepsis results from a bacterial infection, and the article says that 20% to 50% of infected patients die from sepsis.

My interest was piqued, however, because the piece goes on to talk about how a new genetic testing device that the US Food and Drug Administration approved in June could possibly help rein in the disease. That’s because it can reduce the time for diagnosing sepsis from days to hours. And when it comes to sepsis, time is critical.

Sepsis is confirmed by testing for the presence of specific types of bacteria in blood samples from patients and identifying what bacteria, if any, are in the circulation. If they are present, the researchers need to find out if the bugs are resistant to any antibiotic. Unfortunately, all that takes time – time the patient often doesn’t have. As the news story notes,
A 2010 study in the journal Critical Care Medicine found that for every hour of delay in administering antibiotics, mortality rose by 7.6 percent.
The new testing system is called the Verigene Gram-positive Blood Culture Test, marketed by Nanosphere Inc., a nanotechnology company in Northbrook, Ill. NBCNews.com describes the system:
About the size of a small microwave oven, the Verigene Gram-positive Blood Culture Nucleic Acid Test is the first system approved by the FDA to identify quickly certain bacteria responsible for bloodstream infections -- and whether some are resistant to the top drugs used against them. Instead of the three days required for a traditional blood culture panel, results from the Verigene test come back within three hours, identifying up to a dozen specific bacteria known to cause sepsis, including strains of Staphylococcus, Streptococcus, Enterococcus and Listeria.
Of particular importance, the system can catch some particularly nasty bugs, methicillin-resistant Staphylococcus aureus (MRSA; see Maryn McKenna’s excellent Superbug if you really want to terrify yourself on this subject) and vancomycin-resistant Enterococci.

In its press release announcing the Verigene test’s approval, the FDA said that, compared to standard microbiology methods, the Verigene test results “were consistent with traditional blood culture methods in 93 percent to 100 percent of the comparisons.”

The test is remarkably simple, and even automated, requiring a dedicated sample processing instrument and a reader from Nanosphere.

The patient sample is added to a glass slide covered with capture signals that recognize DNA from sepsis-causing bacteria. The capture signals are placed on the glass slide in a defined order, each programmed to recognize only one strain of bacteria. This uniform order helps scientists identify which strain of bacteria, if any, is responsible for the infection. If the patient blood sample contains bacteria, the signals on the glass slide will capture its DNA, and the special scanner and software can detect this capture.   

What sets the Verigene test apart from the previously available tests for sepsis is precisely how they do the detecting. The test adds sub-microscopic gold balls, called gold nanoparticles, to the glass slide. These gold nanoparticles are studded with more capture signals. When bacteria match up with the same specific capture signals, the nanoparticles will attach to that area. This ball gives scientists the ability to more rapidly detect which type of bacteria, if any, is present, and thus select the right course of antibiotic treatment.

The reaction is developed by coating the gold nanoparticles with silver, a process called signal amplification, which increases sensitivity up to 100,000 times, and then hitting it with light. Those spots containing the nanoparticles scatter light; those without it, do not. The effect is so strong, the original paper detected it using a “conventional flatbed scanner,” like something you’d have in your home office.

According to Nanosphere’s website, the whole thing requires less than five minutes’ worth of hands-on time, plus 2.5 hours to get the result. That falls within the necessary time frame to diagnose sepsis and begin life-saving antibiotic therapy.

Hopefully, this is a technology that neither your family nor mine will ever need. But it's nice to know it's there. And now, you know how it works.

(If you’re interested in the research paper that led to this test, from company cofounders Robert Letsinger and Chad Mirkin, both of Northwestern University, you can read it here.)

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