C.diff cases may be twice as high as tests miss infection
The number of cases of the hospital bug C.diff could be twice as high as previously thought as current tests used by the NHS are failing to pick up the infection, experts have claimed.
By Rebecca Smith, Medical Editor Published: 7:15AM GMT 04 Nov 2009
There are around 3,000 cases of Clostridium difficile reported in hospitals in England each month but the true figure could be much higher as the current testing methods miss between 20 per cent and 80 per cent of cases, according to microbiologists.
Prof Gary French, consultant microbiologist at Kings College London and Guy's and St Thomas' Foundation Trust, has carried out research showing that the current test only correctly identifies around 38 per cent of cases of C.diff. Other trials have suggested about half of cases are found.
The research, which is due to be published in the Journal of Hospital Infection, suggests new methods using two-stages, one to screen for the presence of C.diff and if positive another more sophisticated test to establish if the bug is producing the toxins which cause symptoms or is lying dormant.
C.diff is a bacterium that can be found naturally in the gut of some people without causing problems but in others it can produce toxins which trigger diarrhoea. Vulnerable elderly patients and those who have been on antibiotics in hospital are more susceptible and the disease can prove fatal in some cases.
The results from current tests used in NHS hospitals can take several days.
Prof David Persing, consulting professor of pathology at Standford University in California and chief medical officer of Cepheid, a company which produces pathology tests, said his research has shown that the tests only found about 50 per cent of positive C.diff cases.
"The data was quite surprising. The tests are not doing anywhere near as well as we thought. For some strains they are only picking up about 20 per cent of the infections that are there. The vasst majority of patients who are infrected with some of these strains are being missed and are not being put in isolation. There is no attempt to even treat the patient if the test comes back negative," he said.
He said for strain 106, which is common in Britain, the current test only detected around 20 per cent of cases but for the more virulent 027 strain the tests found 80 per cent of cases.
The new tests are more accurate and faster, he said, but they can be three time more expensive. However, by finding positive cases faster, NHS hospitals could cut their infection rates and reduce duplicate tests to save money in the long run.
Prof French also found that the current tests are 'inadequate' and called for new methods to be employed. But he added that patients with symptoms are isolated and treated accordingly without waiting for test results and they may continue to be treated even if the result is negative.
He said: "From our paper and other studies, we show that the present tests are not as reliable as they should be… I think that these tests are really not good enough. We need recommendations to move to a new system and this should be debated."
Prof French said that although new tests may find more cases it should not be taken as a rise in C.diff prevalence but would be the result of more accurate testing. He said the downward trend in C.diff cases shown by mandatory reporting of cases to the Health Protection Agency is probably still the case.
He said: "The hygiene improvements across the board, shown by the dramatic reduction in MRSA rates, means I am convincted taht the reduction in C.diff rates is a true phenomenon.
"If we go to a new test that is more sensitive we are bound to see an increase in reported cases. That will not be a result of poor practice but the result of better testing."
The latest C. Difficile figures show that there were 6,855 cases reported in patients aged two years and over during the April to June 2009. This is a drop of 37 per cent on the same period last year.
Dr Christine McCartney, Executive Director for the Health Protection Agency's Healthcare Associated Infection and Anti-Microbial Resistance Programme, said: “Studies have suggested that different tests have better efficacy rates depending on the strain of Clostridium difficile.
“The Agency works closely with the Department of Health to ensure all infection control guidelines take any new strains of health care associated infection into account to ensure health care settings have the most up to date evidence and research possible to help combat healthcare associated infections.”
Brian Duerden, Inspector of Microbiology and Infection Control at the Department of Health said: "Accurate test results are essential for good patient care. In March this year we issued advice on a two-stage testing approach and reminded trusts that patients should be isolated and treated as Clostridium difficile patients if they were symptomatic, even if they tested negative.
"We will be evaluating the results of this study, along with other studies currently underway, as part of a review into healthcare acquired infection testing. We will continue to work tirelessly to tackle these infections."
Testing methods will be discussed at a symposium at Guy's and St Thomas' Hospital.
New, more expensive tests should be brought in, but hospital managers would need reassurance that any apparent rise in cases found by the new methods should not be seen as poor patient care, they said.
By Ed Susman SAN FRANCISCO -- September 15, 2009 -- Researchers said that hospital-acquired infections with methicillin-resistant Staphylococcus aureus (MRSA) can be largely prevented by identifying carriers of the organism when patients are admitted to the hospital and then initiating aggressive isolation procedures, even if patients are not experiencing disease symptoms but are colonised by the bacteria. Lance Peterson, MD, Microbiology and Infectious Diseases Research, NorthShore University HealthSystem, Chicago, Illinois, said if hospital staff is not aggressive in conducting isolation programs with persons carrying MRSA, the infection control program is doomed to fail. The aggressive program initiated at his hospitals in 2005 resulted in a 70% reduction in MRSA infections rates, and even though the costs associated with the program added to the hospital budget, the resulting savings in preventing infections was triple the cost, Dr. Peterson said here on September 12 at the 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). The study at the 3 NorthShore system hospitals in Evanston, Illinois, revealed that about 7 of every 100 individuals who had MRSA colonisation developed a symptomatic infection. "The biggest risk factor for MRSA infection is to be colonised," he said. The 3 hospitals used real-time polymerase chain reaction testing to screen incoming patients for colonisation with MRSA. Upon presentation at the hospital, patients had their nostrils swabbed for pathogens. If MRSA was detected the patients were isolated and treated with mupirocin for 5 days. Staff treating these patients wore gowns and gloves for contact precautions, he said. Patients were also given 2 antiseptic baths. The polymerase chain reaction test is more expensive than traditional tests, and additional nursing care precautions also added costs to the program, Dr. Peterson said. "The bottom line for us is that if you want to have a successful MRSA reduction program," he said, "you have to have a very aggressive, very rapid, and broad MRSA screening program." Dr. Peterson and colleagues studied 37,179 consecutive patients who underwent MRSA-testing at admission. The prevalence of MRSA was 8.5%, but two-thirds of the individuals were not aware they were carriers of MRSA. "Successful control of any epidemic relies on detection of those harbouring the pathogen and limiting further spread," he said. "The approach to control of the MRSA pandemic is no different. Most persons harbouring MRSA do not exhibit signs of infection and thus to detect all spreaders some surveillance must be done." [Presentation title: Debate: Is Molecular Screening for MRSA Colonization Worth the Cost? Case in Favour. Abstract 408]
Source - ( Sep 15, 2009 )
Sepsis is a major healthcare problem. There are approximately 750,000 cases of sepsis each year in the U.S. And the number is growing.
Sepsis results from complex interactions between infecting microorganisms and host immune, inflammatory, and coagulation responses. Severe sepsis is defined as sepsis with organ dysfunction. Severe sepsis with hypotension, despite adequate fluid resuscitation, is septic shock. Septic shock and multiorgan dysfunction are the most common causes of death in sepsis patients. Mortality associated with severe sepsis remains unacceptably high—20 to 50%. When shock is present, mortality is even higher—40 to 60%.
Distinguishing patients with localized infections or a systemic inflammatory response (SIRS) from those with sepsis is challenging. SIRS is not specific to sepsis and can result from other conditions such as acute pancreatitis and immunodeficiencies. This makes a quick diagnosis, difficult.
Today, blood culture and culture techniques are the gold standard for detection of infection. Physicians order cultures as soon as two or more SIRS criteria are identified. The turnaround time for culture/blood culture is lengthy, ranging from 48 to 72 hours. As a result, antimicrobial therapy administration usually begins before culture results are available.
The choice of appropriate broad-spectrum antimicrobial therapy is tricky because of the rising prevalence of resistant pathogens. Today, this choice is left up to the physician’s intuition. Patients with severe sepsis or septic shock, however, have little margin for error in what therapy they receive. Consequently, there is a huge unmet need for fast turnaround tests that enable early administration of antimicrobial therapy/antibiotics by rapid identification of infection and facilitate choice of antimicrobial therapy through rapid identification and detection of causative pathogen.
Future sepsis diagnostic options include single-analyte immunoassays and molecular identification, for which opportunities exist at both the front and back ends.
Among all single-analyte biomarkers, detection of a protein biomarker called procalcitonin (PCT) in serum holds the most promise. Serum levels of PCT have been shown to increase in patients with an infection; high values will be seen in cases of severe sepsis and septic shock.
Widespread use, however, is lacking. This is partly due to the lack of clinical trials with proper negative controls that differentiate septic from sepsis-like patients. Another difficulty lies with the riskiness of using a cut-off threshold of PCT to rule-out sepsis. Scientia’s research indicates that the possibility of false negatives is daunting and subsequent denial of antibiotic could increase the probability of mortality.
Another potential application of PCT is in therapy monitoring. PCT kinetics can be used to assess the effectiveness of treatment. If PCT levels do not begin to decline in a patient after four days of antibiotic treatment, the physician should consider changing the antibiotic regimen.
B.R.A.H.M.S. owns the IP on PCT and offers the test today along with bioMerieux. Several other immunoassay providers, including Roche Diagnostics and Siemens, have licensed PCT from B.R.A.H.M.S. And are offering it or intend to offer it on their immunoassay platforms.
Molecular identification of sepsis-causing pathogens might prove extremely helpful for rapid identification of pathogens and major antimicrobial resistance determinants. Rapid detection of hard-to-grow pathogens and antibiotic-resistant pathogens such as MRSA and VRE can significantly improve clinical outcome, enabling a narrowing of the spectrum of antibiotic coverage.
SeptiFast, a molecular sepsis test, has been launched by Roche Molecular Diagnostics in Europe. Adoption of this test has been disappointing as a result of its limited coverage of pathogens, automation issues, contamination problem, and cost.
Given the substantial barriers, many molecular diagnostic companies do not plan on taking up the daunting task of introducing a front-end molecular identification test and have resorted to the back end of identification of organisms directly in positive blood cultures instead.
The simplest of these back-end molecular identification tests is the PNA FISH (peptide nucleic acid fluorescent in situ hybridization) test. PNA FISH has the advantage of rapid hybridization kinetics and offers a sensitive way to identify S. Aureus, Enterococcus faecalis, or Candida albicans in positive blood culture samples. Identification is typically done within a few hours after a positive blood culture result is obtained. PNA FISH is available today and is offered by AdvanDx.
Another emerging methodology for identification of organisms in positive blood cultures is real-time PCR. Several companies such as Cepheid (with bioMerieux) are working toward developing such a test.
Sepsis is a complex and life-threatening disease. Significant improvements in the care, management, and treatment of sepsis patients have been realized recently. While early diagnosis remains a challenge and a rapid, sensitive, and specific diagnostic test is still lacking, these new approaches open up a whole new dimension in early diagnosis of sepsis and are likely to evolve into solutions for this major unmet need.
Source - ( Jul 16, 2009 )
Tuberculosis (TB) has taken a backseat over the last few decades as it has not received the funding appropriate to such a major health threat to the developing world. The World Health Organisation (WHO) published statistics last month showing that worldwide TB rates are stabilising at approximately 14 million cases, comprising one-third of the world’s population.
There are, however, a few countries where TB rates are increasing. The Health Protection Agency (HPA) has released statistics showing that the UK has seen a 2% increase (the only European country where TB is actually on the rise) and in African countries where HIV/TB co-infection is rife, TB deaths have quadrupled over the last 15 years. Clearly, tuberculosis is making a comeback - the disease is stronger now than ever before, and is rapidly becoming more drug-resistant, usually by gene mutations. In fact, much of the antibiotic resistance observed among TB strains is multi-drug resistance (MDR), showing resistance toward at least two first-line drugs. TB is second only to HIV as the world’s deadliest infectious disease, claiming a life every 20 seconds.
One of the key obstacles in controlling TB infection is the lack of fast and accurate diagnostic methods, particularly in areas of the world with the greatest disease burden. This article will examine those current diagnostics and reveal details of a new test that is set to revolutionise the way that TB is diagnosed and, therefore, controlled throughout the world.
Over the last year, the World Health Organisation has expressed concern that they may not be able to reach the targets for TB control as defined in the UN’s Millennium Development Goals (MDG’s). Those targets for 2015 included minimum requirements for cases detected and treated and required falling rates of TB incidence. Additionally, as defined in 2006 by the Stop TB Partnership, a global consortium of public health, non-government organisations, World Bank, pharmaceutical and other corporate stakeholders, governments, and academic institutions, prevalence and mortality rates should be decreased to one-half of the 1990 rates. This would essentially mean that 50 million people would receive treatment and 14 million lives would be saved.
As we know, early detection and proper treatment are essential to combat TB. UN Secretary-General, Ban Ki-Moon, argued that although “the epidemic is continuing its decline, the [global] rate of decline is far too slow, Unless we accelerate action, the numbers of those falling ill will continue to grow.” A 2008 report stated that “the detection rate increased only marginally to 61%, short of the 65% benchmark for 2006 contained in the Stop TB Partnership Global Plan and the ultimate target of 70%.”
One-third of TB cases come from Sub-Saharan Africa and Southeast Asia, where the main attributable factors are widespread poverty and a lack of adequate public healthcare.
People who have TB, or live in poverty, can often become mired in a vicious circle of continuous proliferation of both. TB most commonly attacks people in their working years crippling their ability to earn a living. Additionally, the costs associated with healthcare for TB can put families of sufferers under tremendous financial strain. This has a particularly significant impact on children who often become malnourished and have to leave school to take care of their family. In some cases, these children ultimately become orphans.
In turn, people living in poverty who cannot afford or access healthcare often share living space with many people, some of whom are already infected with TB. Spread of infection becomes much more likely in such settings.
There is a strong connection between HIV and TB. A third of all HIV/AIDS sufferers are co-infected with TB. The WHO Global TB Report stated that approximately 1.37 million HIV/AIDS sufferers were diagnosed with TB in 2008 - indeed TB is the leading cause of death amongst HIV sufferers. Shockingly, new data show that 25% of all TB deaths are HIV-related, double the amount previously thought.
Optimal TB management requires rapid detection, treatment, and prevention - but current technologies are outdated and impractical. The most commonly used methods have not changed in more than 125 years. According to the WHO, “only 2% of multi-drug resistant TB (MDR-TB) cases worldwide are being diagnosed and treated appropriately.”
The current testing method begins with spreading the patient’s sputum on a glass slide, treating the material with a special stain, and observing the slide under a microscope to detect the stained bacteria. The stain does not wash off the bacteria on the slide even when an acid solution is used, hence the organisms are called acid-fast bacilli (AFB). But this method, as practiced in high-burden parts of the world, fails to detect half of all active cases; a failure rate that is even higher in those co-infected with HIV. Tests that are more accurate exact a price, both monetarily and in the prolonged length of time it takes to achieve accurate detection of the TB bacteria by cultivating them in the laboratory. Due to the slow growth rate of the TB organism (the bacterium has a doubling time of 24 hours), growing the organism in culture can take weeks before results are available. It then takes even longer to determine if there is drug resistance, because the positive culture requires a second cultivation in the presence and absence of antibiotics in order to determine which antimicrobial agents are effective in inhibiting its growth. Employing all these procedures currently required to diagnose drug-resistant TB means that results may not be available for months.
Unfortunately for many patients in the developing world, this amounts to a post-mortem diagnosis, particularly as they are often co-infected with both TB and HIV - a rapidly fatal combination. Additionally, because diagnosis takes so long, these patients are sent back into the community, rather than isolated and treated appropriately, allowing for further transmission of the organism within the community in the local area.
In most of the developed world, isolation of patients with TB is implemented to prevent transmission to surrounding family and communities. However, even in the UK there are currently no guidelines advocating isolation during the time that the laboratory testing is being conducted, making a rapid diagnosis even more necessary.
Until now, if a clinician were to request a quicker TB diagnostic method than culture, accuracy would suffer. Sputum smear testing alone can theoretically produce results within a day. However 30% or more of patients whose sputum is smear-negative ultimately reveal positive cultures in follow-up tests, proving this diagnostic method to be highly insensitive and dangerously inaccurate. Missed diagnoses via smear testing are estimated to contribute to as much as 20% of newly transmitted TB infections. And in an unexpected twist of fate, patients with HIV/TB co-infection are actually more likely to be smear-negative but to progress rapidly to a fatal outcome.
As World TB Day arrived at the end of last month, Ki-Moon called for faster action to combat TB on a global scale. He highlighted the need for infection prevention, early detection, and worldwide availability of treatment, whilst calling for more effort to combat MDR-TB, XDR-TB (extensively drug-resistant TB), and the TB/HIV co-epidemic.
With this in mind, he called for organisations to come together and develop diagnostic solutions that will prevent the spread of the disease. Specifically, the WHO has called for faster and more accurate diagnostics based on the detection of specific DNA patterns in a gene called rpoB, found in all TB bacteria, that is considered to be a surrogate marker for MDR-TB.
In line with these announcements, a number of organisations have collaborated to develop a new diagnostic test for TB. The new test detects TB in less than two hours, is highly accurate, and has recently become available in Europe. The test is run on Cepheid’s GeneXpert System, a leading molecular testing platform, and was developed jointly by Cepheid, the Foundation for Innovative New Diagnostics (FIND), the University of Medicine and Dentistry of New Jersey (UMDNJ), and the US-run National Institute of Allergy and Infectious Diseases (NIAID).
Not only is the advanced technology able to detect the TB organism directly from sputum, it can also simultaneously detect rifampicin resistant strains of the infection via the presence of mutations in the rpoB gene, which is generally used as a surrogate marker for multi-drug resistance. And the test boasts unprecedented levels of sensitivity for detection of both smear-positive and smear-negative TB cases. Especially for HIV co-infected patients, the latter feature could be a life-saver.
This new test is one of the most important diagnostic developments to have occurred in many years. It is the most technologically advanced test for TB ever developed, yet it is simple enough to perform in all corners of the world, including resource-limited settings in which it is most needed.
When an individual is suspected of having a TB infection, the first step is often a chest X-ray. If the chest X-ray is suspicious, the patient is asked to cough and produce a sputum specimen, which is mixed with a solution that kills the TB organisms and placed into a small plastic GeneXpert cartridge. The GeneXpert System carries out steps that would have, until recently, required a dedicated laboratory facility and highly trained molecular diagnostic specialists. Within the cartridge, specimen processing and reagent mixing involving dozens of micro-pipetting steps are used to carry out nested real-time polymerase chain reaction (PCR), a method to multiply DNA in a test tube dramatically faster than occurs naturally in cultures. This reaction amplifies a DNA signature sequence that is specific to TB complex bacteria. DNA amplification and detection occur simultaneously within about 90 minutes. Because the test procedure is so simple, it is possible to run a STAT test on demand for patients with X-ray findings suspicious for TB, thus maximising the medical value of the test. At this time, all other PCR-based tests require multiple hands-on processing steps that necessitate performing the tests in batches.
Building on an ingenious protocol developed by Dr David Alland, M.D. And his colleagues at UMDNJ, the team engineered a protocol inside the GeneXpert cartridge that detects the presence of 5 different mutations in the core of the rpoB gene, now proven to detect virtually all rifampicin resistant strains of TB. Because rifampicin resistance is almost always present when there is resistance to other drugs, this result can be used to predict MDR-TB. Still more important is that the presence of rifampicin resistance predicts failure of first-line therapy, guiding the clinician to the most effective choice of second-line treatment and potentially avoiding costly treatment failures that lead to progressive disease and continued spread to others.
Tuberculosis is not an infection that is going to vanish overnight and, contrary to popular belief, it is not a disease from the 19th century that we no longer need to worry about, although it should be. It is a tragedy that we have not yet managed to eradicate this devastating infection from the world, both in developing countries and in our own supposedly developed country. Its close links with poverty and the HIV virus make it a much more widespread and serious issue in Africa and Southeast Asia, but it is also a concern in the UK and Europe. With over 8,000 new cases of TB reported every year in the UK, we are seeing the number of cases increase, bucking the global trend. It is my sincere hope that this new diagnostic test, which will soon be available throughout the world, will mark the tipping point when we finally start to win the battle against TB.
Source - ( Jul 24, 2009 )
By Geri Aston
When MultiCare Health System started rapid screening for methicillin-resistant Staphylococcus aureus (MRSA) in late 2007, officials paid close attention to one intensive care unit because of its history as an infection source. In the first quarter of 2008, before the screening protocol was consistently adopted, the medical-surgical ICU in question had three cases of health care-associated MRSA, says Marcia Patrick, R.N., MSN, infection control director for MultiCare Health System, Tacoma, Wash. In the second through fourth quarters, one patient was colonized with the bacteria after admission, but no patients became infected in any of the system’s five ICUs. “Early identification means we can get positive patients into isolation quickly,” Patrick says. “With good use of gowns, gloves and hand hygiene, we reduce the risk to other patients.”
Because of heightened attention to prevention of health care-associated infections (HAI) and advances in testing technology, many hospitals are considering making the move to rapid tests. But the decision is a complicated one that depends on an individual hospital’s circumstances, say hospital officials, infection control experts and test makers.
Rapid tests fall into two broad categories: screening (for the presence of an infection) and diagnostic (to determine the source). Major developments have occurred in both categories in recent years that have expanded hospitals’ options.
When it comes to rapid screening tests, most attention is on MRSA, says Patrick, who is an Association for Professionals in Infection Control and Epidemiology board member. “That’s probably the biggest thing health care facilities are struggling with, in terms of do we or don’t we want to go the rapid route.”
When making the decision, it’s important not to look at the tests in isolation, says Susan A. Levine, Ph.D., vice president of health technology research and consulting for Hayes Inc., a health technology assessment company in Lansdale, Pa. “These tests are very clever, but it’s really more important to have a system in place to support them and even to figure out if you need them.”
Hospitals should make sure they have a good infection control program in place before deciding whether to move to a rapid test, Levine says. Instituting proper hand hygiene, wound care and environmental cleanliness standards might solve most of the problem.
If a hospital has a strong infection control system and low HAI rates, it might not make sense to bring in a rapid MRSA screening test and its associated costs, says Daniel Diekema, M.D., an epidemiologist at the Iowa City VA Medical Center and a professor of internal medicine and pathology at the University of Iowa Carver College of Medicine. “You have to work with your clinicians and laboratorians up front to decide if it’s justified to bring a test on board,” he says. “Will it make a clinical impact?”
If all the infection control protocols are in place and a problem persists, a hospital might want to bring in a rapid screening test, says Diekema, who chairs the Society for Healthcare Epidemiology of America’s scientific meeting planning committee.
The question then becomes which patients to test and when. This decision, too, depends on the hospital’s circumstances. The options include screening all admitted patients or just those admitted to specific areas. The Veterans Health Administration has required screening of almost all inpatients since 2007. MultiCare tests all ICU patients, says Patrick. The system also began screening certain surgical patients, such as those getting total joint replacement or spine surgery, because infection in those cases can be so medically devastating.
Some hospitals opt only to screen patients with risk factors for carrying or getting MRSA in the hospital, such as patients transferred from nursing homes or immunocompromised patients, Levine notes. However, not all at-risk patients are easy to identify, especially as MRSA has spread into the community, says David Persing, M.D., Ph.D., chief medical and technology officer for test-maker Cepheid, Sunnyvale, Calif., (www.cepheid.com).
Hospitals have several options from which to pick once they’ve made the decision to go with a rapid screening test. Results from time-honored standard cultures take about 48 hours. But newer technology allows labs to grow cultures in 18 to 24 hours using chromogenic media. Hospitals also could go with real-time polymerase chain reaction (PCR) tests, which rely on gene amplification and provide results in two hours or less.
Sizing up needs
In evaluating their choices, hospitals should look at a number of factors, including test performance, ease of use and cost. Other questions to ask are whether the test can be run with current lab personnel, given their numbers, training, lab space and certification; how often tests would be run; how much room is available to isolate positive patients; and what kind of technical support and training the test manufacturer provides.
The two available PCR screening tests perform comparably well, several experts say, so other issues come into play. One is frequency of testing. Cepheid tests can be done on demand on individual patients, while Becton, Dickinson and Co. (BD, www.bd.com) tests are run in batches, so they’re done less frequently. For example, MultiCare uses the BD test, which the lab runs once a day at 11 a.m., with results coming back between 1:30 p.m. And 2 p.m., Patrick notes.
On-demand tests give hospitals more flexibility, but they pose a lab staffing question, she says. “Do you have the manpower for someone to step away from their routine work and go set one of these up to get an immediate result?”
Many hospitals avoid the big capital expenditure with “reagent rental” agreements, says Barbara Kalavik, spokeswoman for BD, Franklin Lakes, N.J. Under this approach, the hospital finances use of the PCR machine by committing to the manufacturer’s reagents and paying somewhat more for them.
Two other considerations are test volume and the lab’s turnaround time. Depending on those factors, batched PCR test results could potentially have the same turnaround time as the less-expensive chromogenic plates, Patrick notes.
Hospitals also have to address whether they plan to isolate patients while awaiting MRSA screening test results and if they have space to do so, Levine says. If the hospital has plenty of single-bed rooms in which patients are essentially isolated, a slower test might be a viable option. Other hospitals may not have the space to pre-emptively isolate patients for 18 or more hours, in which case the more rapid PCR test might be the way to go.
“A lot of hospitals have at least considered the [PCR] test because it really does speed up the process,” Levine says. “It becomes reasonable when someone is being admitted for surgery to have the test results before surgery.”
Most U.S. Hospitals do not isolate patients pre-emptively, Persing says. Instead, they make the bed assignment, wait for the test results and then react. In hospitals where patients typically share rooms, that practice poses an exposure risk when a patient tests positive for carrying MRSA, he says. Although it’s more expensive up front, getting the test results before bed assignment can save money later in bed management, Persing argues.
The two PCR test manufacturers only have U.S. Approval to sell rapid screening products for MRSA. However, last year both BD and Cepheid introduced products in Europe that screen for vancomycin-resistant enterococci. Cepheid plans on submitting its test for Food and Drug Administration (FDA) approval, Persing says. BD’s product currently is under FDA review, Kalavik says.
An advantage of the PCR machines is that they can be used to detect other bacteria as tests for those organisms become available, Patrick says. For example, MultiCare plans to use BD’s Clostridium difficile PCR diagnostic test. The company announced in January that it had FDA clearance for U.S. Marketing.
Rapid diagnostic tests for HAIs are quickly evolving. The technologies allow for quick identification of the organism causing a patient’s bloodstream infection. This means clinicians can prescribe the right antibiotic more quickly, which benefits the patient and helps prevent antibiotic resistance, several experts say.
Last year, BD and Cepheid received FDA approval for their rapid PCR diagnostic tests for methicillin-sensitive S. Aureus (MSSA) and MRSA. The tests detect the organisms in blood culture bottles showing gram-positive cocci. The products yield results in two hours or less, depending on the maker, as compared with the several days traditional tests take. Knowing whether the patient is infected with resistant or nonresistant staph allows the clinician to tailor antibiotic therapy accordingly, Persing says.
Another rapid diagnostic testing option is peptide nucleic acid fluorescence in situ hybridization (PNA FISH). The technology uses fluorescent molecular gene probes that target specific microbes to identify which organism is causing a patient’s bloodstream infection. Like PCR tests, PNA FISH is run using a sample from a positive blood culture. Results take about two and a half hours.
Beyond MRSA testing
The technology can detect a number of bacteria, most of which can cause bloodstream infections in hospitalized patients, says Graeme Forrest, M.D., assistant professor of medicine in the Oregon Health and Science University division of infectious diseases. These include S. Aureus, enterococci, streptococci, pseudomonas and Escherichia coli. PNA FISH also tests for yeast and fungal infections.
PNA FISH products by test manufacturer AdvanDx (www.advandx.com ) cover 95 percent of organisms causing bloodstream infections, and the Woburn, Mass., company has plans to develop tests for the remaining 5 percent, says marketing director Joen T. Johansen.
When evaluating PCR and PNA FISH technology, hospitals should consider a number of factors, Forrest says. They include: “what works within the resources of your center, what’s practical, what can be achieved and what can fit in the space you have. It also depends on your tech people—what their qualifications are.”
The technologies have some major differences. One is cost. PNA FISH requires less investment up front, about $4,000 to $4,500, Johansen says. After that, the reagents cost about the same as PCR tests, Forrest notes.
The two types of tests have advantages and disadvantages in terms of which organisms they detect. A major limitation of the PNA FISH staph test is that it does not show whether the bacteria is methicillin resistant, Forrest says. On the plus side, PNA FISH products are available for a wider range of bacteria.
The PNA FISH enterococci test differentiates between E. Faecalis and E. Faecium, which is often vancomycin resistant (VRE). According to the Centers for Disease Control and Prevention, enterococci cause about one out of every eight infections in hospitals, and about 30 percent of those are VRE.
The PCR diagnostic tests’ main disadvantage is that its U.S. Use is limited to only staph in the case of Cepheid, and staph and C. Difficile for BD. However, that could change soon. Cepheid’s rapid diagnostic test for C. Difficile is available in Europe. The company is submitting its product, which yields results in 45 minutes and can identify the strain responsible for hospital epidemics, to the FDA, Persing says. He expects approval before the year is out.
Cepheid also has released in Europe a rapid diagnostic test for tuberculosis. The sputum test not only determines the presence of the bacteria but identifies whether it is drug resistant. It takes about 45 minutes, rather than between four and six weeks for the traditional technique, Persing says. He anticipates that the company will begin the U.S. Regulatory approval process next year.
When it comes to diagnosis of bloodstream infections, Forrest believes hospitals should move to rapid products for the clinical benefit. “The microbiology labs in some small centers are still doing the same things we’ve been doing for the past 80 to 90 years.”
The main barrier is the price. “Unfortunately with hospitals, it’s a cost to the lab. They’re really tightening up any costs at the moment,” Forrest says.
He urges hospitals to take a long view. “If we can shorten lengths of stay, shorten the use of unnecessary antibiotics, have less ICU stays because [patients] get the right drug, it’s going to save a lot of money on the other end.”
Hospitals interested in investing in rapid tests should keep an eye on the horizon, Levine says. Some interesting products could be hitting the market in the coming years. One is a five-hour MRSA screening test that uses bacteriophages, viruses that infect bacteria.
MicroPhage Inc. (www.microphage.com ), the test’s maker, announced in January that it had completed its first multicenter clinical trial. The company, located in Longmont, Colo., predicts the product will be available to U.S. Hospitals later this year.
A diagnostic MRSA test under development uses metal ions to identify the bacteria’s genes without the need for the gene amplification technique on which PCR tests rely. If approved, this metalized-DNA approach could be used by labs that lack the sophistication to run PCR tests, notes Adnavance (www.adnavance.com ), the San Diego company developing the test.
Rapid tests for HAIs are still a new phenomenon, Levine says. The first quick-screening test for MRSA was approved in 2004 and the second in 2007, she notes. In the last quarter of 2008, 447 Cepheid GeneXpert Systems were in place in the United States, says spokeswoman Darwa Peterson. About 100 U.S. Labs are using AdvanDx’s PNA FISH products, Johansen says.
“What we’re seeing is just the start of these rapid tests,” Levine says. “I think they’ll become more user-friendly and easier to use at the point of care, and that would all be good.”
Source - ( Jul 23, 2009)
MRSA Survivors Network, the Chicago-based nonprofit and the official organization that launched World MRSA Day earlier this year is building momentum in the US, the UK and worldwide in its humanitarian grass-roots effort to raise awareness of the MRSA epidemic. "As governments and world agencies continue to put their focus on swine flu and prepare to spend billions of dollars on it as they did with Avian flu; the true epidemic/pandemic, MRSA continues to be virtually ignored", states Jeanine Thomas, president of MRSA Survivors Network and the National Spokesperson for MRSA. "It is unconscionable what has been allowed to happen and MRSA has been swept under the carpet in healthcare facilities for decades and the purpose of World MRSA Day is to raise awareness." Healthcare industry companies are stepping up and sponsoring World MRSA Day in the US and in the UK to raise awareness and save lives. In the U.S.; 3M, Tec Labs, Cepheid, Pfizer and others have lent their support and all have become true heroes in this movement to save lives. The inaugural pre-launch kick-off event in the U.S. Will be held Oct. 1st at Loyola University in Chicago with an international press conference, followed by the event. MRSA Action UK, who shares and alliance with MRSA Survivors Network are planning their event for Oct. 2nd. MRSA activists are organizing and holding events in their communities on Oct. 2nd and throughout October, MRSA Awareness Month. Activists can list their event on the official site- www.worldmrsaday.org. MRSA Survivors Network and fellow activists are pushing for immediate action, legislation, funding, more stringent and pro-active infection control measures and enforcement by the World Health Organization, the Centers for Disease Control and governments to stop the massive loss of life and human suffering from preventable infections. World MRSA Day is embracing all survivors and their families who have suffered or lost a loved one from any multi-drug resistant infection. Jeanine Thomas of MRSA Survivors Network was the first advocate in the U.S. To raise the alarm about MRSA and other healthcare-acquired infections and began her crusade in 2003. Ms. Thomas is a survivor of MRSA, sepsis, osteomyelitis and C. Diff and became critically ill and nearly died from the results of ankle surgery. She now lives with chronic MRSA infections. Source MRSA Survivors Network
<p><a href="http://www.medicalnewstoday.com/articles/154878.php" target="_blank"><b>Source - ( Jun 01, 2009 )</b></a></p> <p> </p>
“Fast and accurate diagnosis of MDR TB is critical if the increase in this especially deadly form of TB is to be slowed,” says David Alland, M.D., of the University of Medicine and Dentistry of New Jersey, in Newark. “It is important to distinguish patients who have drug-susceptible disease and can be started on a routine regimen of one or more TB drugs from those whose infections are caused by drug-resistant strains of M. Tb. If the latter can be identified as soon as they come to the clinic for treatment they can be safely separated from the rest of the hospital patients and will not spread MDR TB to others.”
Dr. Alland and his collaborators at Cepheid, Inc., of Sunnyvale, Calif., have had success identifying MDR TB using a test that they say is well suited to conditions in countries where health care resources are limited and where TB is widespread. Dr. Alland explains that the testing method they have developed using a special assay is essentially a biotech lab in a small plastic cartridge. The test quickly, automatically, and accurately tells doctors whether a sample of patient sputum (material expelled from the lungs and throat by coughing) contains drug-resistant or drug-susceptible M. Tb. The test is contained in a sealed cartridge to protect the patient sample and prevent contamination of the sample. A contaminated sample could result in inaccurate or false test results.
One early hurdle for the researchers was finding a simple way to extract M. Tb DNA from the thick, sticky sputum. Ordinarily, processing sputum is labor-intensive and requires expensive equipment, such as centrifuges, which are not always available in resource-limited settings. After some effort, the scientists devised a way to liquefy sputum with chemicals that can be added directly into the sputum collection cup. The sputum can then be easily transferred into the sample processing cartridge using a simple plastic pipette, eliminating the need to spin samples in a centrifuge.
After the M. Tb DNA is extracted from the sputum sample it is amplified for testing, through a technique called real-time polymerase chain reaction. When the sample is large enough, five kinds of lab-made fluorescent molecular tags, called beacons, are applied simultaneously. Each beacon glows in a different color when it attaches to M. Tb DNA. In the presence of drug-susceptible TB, all five colors are visible. If any one of the colors is absent at the end of the test, it means the sample contains drug-resistant M. Tb. Dr. Alland and his colleagues reported that their molecular beacon assay took less than 2 hours and correctly identified rifampin-resistant TB in almost all of the samples tested.
In 2004, the scientists used the molecular beacon assay to correctly distinguish rifampin-resistant and rifampin-susceptible strains of M. Tb in sputum samples taken from patients in areas of high TB incidence in north India and Mexico. Rifampin is one of the first line drugs used to treat TB. It is also one of the drugs to which strains of M. Tb have developed resistance, and importantly, resistance to this drug has been shown to be a reliable marker for MDR TB.
Along with Dr. Alland and his collaborators from Cepheid, Inc., the partnership now includes Geneva, Switzerland-based Foundation for Innovative New Diagnostics. The group has initiated field tests of their all-in-one diagnostic cartridge in Azerbaijan, India, Germany, Peru, South Africa and Uganda.
El-Hajj, H. H. Et al. Detection of rifampin resistance in Mycobacterium tuberculosis in a single tube with molecular beacons. J Clin Microbiol. 2001 Nov;39(11):4131-7.
Varma-Basil, M. Et al. Rapid detection of rifampin resistance in Mycobacterium tuberculosis isolates from India and Mexico by a molecular beacon assay. J Clin Microbiol. 2004 Dec;42(12):5512-6.
Thirteen years after Roche launched the industry with a test for HIV load based on transcript abundance, molecular diagnostics is in full flower. A $3.3 billion market growing at 17 percent annually, the field includes assays for disease predisposition, screening, diagnosis, prognosis, monitoring, and predicting treatment efficacy, using markers ranging from SNPs to methylcytosine, messenger RNA to microRNA. Bringing digital power to traditional analog medicine, the field "is absolutely going to revolutionize health care," says Harry Glorikian, managing partner at Scientia Advisors. "I believe it with every fiber in my being."
By Jeffrey M. Perkel
Inclusion of companies in this article does not indicate endorsement by either AAAS or Science, nor is it meant to imply that their products or services are superior to those of other companies.
About a year ago, 48-year-old Jeff Gulcher's doctor called to say Jeff had cancer. His prostate was teeming with cells scored at Gleason-6, the high end of intermediate grade. The recommendation: radical prostatectomy.
The diagnosis was shocking. Gulcher wasn't at risk as far as he knew: he had no family history of early prostate cancer, and he had no symptoms. What he did have was a suspicious genotype.
Gulcher had paid $985 for the deCODEme test, a genome-scale single nucleotide polymorphism screening service from deCODE Genetics. The test uses Illumina microarrays to profile about a million loci, reporting back on the relatively small number of conditions that can be tied to the results. Scattered across 10 chromosomes, the test's 13 prostate cancer–related markers suggested that Gulcher's lifetime risk for the disease is about twice the average, or 32 percent. That's not a diagnosis, but a warning, like elevated cholesterol. It means, pay attention.
Gulcher's physician recommended a prostate specific antigen (PSA) test. Such screening typically doesn't begin until age 50. In this case, the test came back at 2.0 ng/mL, "in sort of the mid-normal range," Gulcher says. Normally harmless, that value plus the genotype data prompted his urologist to refer Jeff for a biopsy.
"I'm thinking, there's no way I have cancer," Gulcher recalls. "I'll go through the motions, have the biopsy. But just having this higher risk doesn't mean I'm going to get prostate cancer by any stretch of the imagination."
Fortunately, Gulcher didn't rely on his intuition, and the surgeon excised his tumor intact; postoperatively, it was reassessed at high grade. PSA score down to zero, Gulcher appears to have dodged a bullet, all thanks to a molecular diagnostic that he actually helped develop. Gulcher is deCODE's co-founder and chief scientific officer.
"This genetic test is reclassifying people who are thought to have average risk into somebody who really is at higher risk, and may benefit from extra surveillance," Gulcher says.
That, in a nutshell, is the promise of molecular diagnostics (MDx). Whether stratifying patients for heightened or diminished scrutiny, advising doctors on treatment decisions, or diagnosing disease, the field is redefining medicine.
Every diagnostic is molecular, whether measuring cholesterol for heart disease, radiolabeled glucose for brain imaging, or mass spectrometric peaks for ovarian cancer. So just what, exactly, is a "molecular" diagnostic?
According to Harry Glorikian of Scientia Advisors, the term generally applies to assays that detect nucleic acids, whether single nucleotide polymorphisms, mutations, or RNAs, with a sprinkling of "certain very high-quality, high-value protein assays," as well.
They come in a variety of flavors. Besides predisposition tests like deCODEme, there are assays for diagnosis, prognosis, prediction of drug response, and disease monitoring. Such tests, says Glorikian, represent a fundamental break from what he calls the traditional "gestalt" diagnostic approach. Blood pressure, temperature, and blood chemistry "are not digital indicators but analog indicators," Glorikian says, "where [the doctor] uses the computer between his/her ears, looks at all this stuff, bins it together, and says aha! This is what I think."
By contrast many MDx tests provide quantitized, digital data, as well as actionable results.
Take Down syndrome. Traditionally, a woman's likelihood of having a baby with trisomy-21 is first assessed by noninvasive screens based on maternal serum proteins and ultrasound. Yet these assays provide risk scores rather than absolute diagnoses, and must often be supplemented with more accurate, but also invasive tests such as amniocentesis, which literally count fetal chromosomes.
Sequenom's trisomy-21 MDx, set for launch later this year, blends these two approaches. Using mass spectrometry to count fetal chromosome 21–derived transcripts in maternal blood, the test is both noninvasive and quantitative—though not, per se, digital; the test measures the ratio of maternal and paternal alleles from chromosome 21.
"It's an absolute result," says Harry Stylli, Sequenom's president and CEO. "You're not dealing with a risk score." As a result, high-risk pregnancies may be properly managed, while the number of pregnancies unnecessarily subjected to invasive procedures—currently about 140,000 per year, Stylli estimates—"will dramatically decrease." [Editor's Note: It came to our attention shortly after publication of this article that the release of Sequenom's test has been delayed due to questions about some of their test data.]
Perhaps no genes more starkly illustrate the actionable power of MDx than BRCA1 and BRCA2. Mutations in these genes carry such high risk of breast and ovarian cancer (about 82 percent) that some carriers opt for prophylactic radical mastectomy, using Myriad Genetics' BRACAnalysis blood test to help guide their decision.
Based on full-length Sanger dideoxy gene sequencing, BRACAnalysis is an unusual test; sequencing is more typically suited to research labs. Yet unlike proteins or transcripts, Gulcher notes, DNA "is the only stable molecule in your body." It enables Myriad to pick up novel mutations. "Unfortunately there are a very large number of mutations in the genes that we look at, so it is not a mutation-specific test, it is a full DNA sequence test," explains Pete Meldrum, Myriad's president and CEO.
Myriad offers the test as a lab-developed "home brew" assay available through the company's Clinical Laboratory Improvement Amendments (CLIA)–certified facility in Salt Lake City, Utah. Not yet vetted by the US Food and Drug Administration (FDA), such tests can only be offered by the lab that develops them.
In this case, results come back in about 10 days. That's not generally a problem for predisposition tests. But sometimes, and especially when confronting acute medical issues, patients don't have that kind of time.
"In general, the faster the results become available, the more likely it is that they are going to be actionable," says David Persing, executive vice president and chief medical and technology officer at Cepheid.
When speed is required, real-time or quantitative PCR (qPCR) delivers. Most labs have a PCR machine, and most lab techs are competent to run them.
"Real-time PCR is quite a forgiving technique," says Stephen Little, CEO of DxS. "You can put different levels and quantities of samples into the test and it will still give a good result."
Even so, clinical labs often delay crucial tests because they must process them in batches. Cepheid's GeneXpert system was built to circumvent this problem, says Persing. A modular, independently addressable real-time PCR system, the GeneXpert is "the first sample-in, answer-out machine for real-time PCR to hit the market," says Glorikian.
Anyone can use it, Persing says. In one study, nurses running the company's Group B Streptococcus test in the labor and delivery suite "delivered results that were highly accurate, and were as reliable and as good as the ones delivered by the lab."
In part, that's because there's no sample prep; the system processes raw samples straight to analysis. Results can arrive in as little as 31 minutes, fast enough to catch patients before they leave the doctor's office.
Cepheid's new Xpert MTB/RIF assay reports in less than two hours both if an individual has tuberculosis and whether it is resistant to rifampicin. Traditional culture methods take weeks to make that assessment, says Persing, during which time patients may unwittingly spread the infection.
Cepheid's assays are mostly based on Applied Biosystems' TaqMan reagents, modified oligonucleotides that contain a fluorescent dye on one end and a quencher on the other. During PCR, this oligo binds its target DNA between the two amplification primers, where it is chewed up by the polymerase's 5' to 3' exonuclease activity, separating dye from quencher in a burst of fluorescence.
DxS uses an alternative detection reagent, called a "scorpion" probe, for its TheraScreen assays.
A scorpion, says Little, is "a self-quenching molecule." A hairpin with a PCR primer at its 3' end, the scorpion serves as a 5' PCR primer. The hairpin is complementary to part of the amplified sequence, and like a TaqMan probe bears both a fluorophore and a quencher. In the absence of amplification, the closed hairpin keeps the two dyes in close proximity, dousing fluorescence. But after amplification, the probe can denature, unfold like a scorpion's tail, and hybridize to the amplified segment. In the process, the fluorophore and quencher dissociate.
"That's the signal that the reaction has taken place and we use it to signal the presence or absence of the mutations that we look for," says Little.
In the case of DxS's K-RAS and EGFR assays, the resulting data can guide treatment. Knowledge of a K-RAS mutation helps oncologists choose between cetuximab and panitumumab in colorectal cancer, while different mutations in EGFR affect which works better for nonsmall-cell lung cancer (NSCLC), gefitinib or erlotinib.
Though many MDx probe single nucleic acids, a small but growing number profile panels of genes simultaneously.
"As our understanding of genetics increases, we are going to learn that most diseases are multigenic in nature," says Amit Kumar, president and CEO of Combimatrix, which develops MDx based on array comparative genomic hybridization; "It's not just one gene that's causing a particular illness or disease; it's a combination of multiple genes functioning together."
Three such tests have been cleared under the FDA's "in vitro diagnostics–multivariate index assay" guidelines, all based on gene expression. XDx's 20-gene AlloMap test uses reverse transcriptase (RT) PCR to monitor heart transplant rejection; Agendia's 70-gene MammaPrint microarray assay predicts whether breast cancer patients are likely to relapse and benefit from chemotherapy; and Pathwork Diagnostics' Tissue of Origin test uses a 1,500-gene array to determine the source of a primary tumor in patients that present only with metastases.
"In order to effectively treat a metastasis, you have to treat it in the same way that you treat the primary tumor," explains Ronen Tamir, chief commercialization officer at Rosetta Genomics, whose "miRview mets" test addresses the same problem using a 48-gene RT-PCR assay. In other words, a breast tumor that metastasizes to the colon should be treated as breast cancer.
Such tests may be less digital, perhaps, than the Down syndrome or BRCA tests—they sometimes provide probabilities rather than certainties—yet they still can help doctors make smarter treatment choices.
According to Steve Shak, chief medical officer at Genomic Health, whose 21-gene RT-PCR–based Oncotype DX assay also predicts breast cancer relapse, the most common treatment for women with node-negative, estrogen receptor–positive breast cancer is chemotherapy. Yet only about 4 percent of patients benefit from that option; the rest would do just as well with surgery plus hormonal therapy alone.
Now, using Oncotype DX, about one-third of treatment decisions change, Shak says. "Some women with high recurrence scores who might have been treated with hormonal therapy alone are then given hormonal therapy plus chemotherapy," he says. Similarly, "there are many women who might have considered chemotherapy but based on the results will be confident in getting hormonal therapy alone." Agendia cites similar numbers for its MammaPrint diagnostic.
Yet when it comes to multivariate MDx, array-based assays like MammaPrint are relatively rare; frequently, developers use arrays for test development, reverting to RT-PCR once the hard work of biomarker identification is done. Such was the case for Oncotype DX and AlloMap.
"The thing with arrays is they are a little bit clunky to use, whereas RT-PCR, if you can use it, is a much easier technology to fit into a lab," says Little. "Ease of use and convenience are very important considerations when you move into diagnostics."
Ease of use and convenience are especially important when it comes to more esoteric markers, such as DNA methylation or microRNAs.
LabCorp's ColoSure test measures methylation of the vimentin gene in stool samples. Epigenomics is developing a blood-based assay for SEPT9 methylation. Both are early indicators of colon cancer, and both are based on qPCR detection of bisulfite-treated DNA (in which unmethylated cytosine is converted to uracil, while methyl-C remains unmodified).
"Having a very innovative test with a novel analyte [DNA methylation], we decided to be rather conservative when it comes to the assay technology," says Achim Plum, senior vice president for corporate development at Epigenomics.
Slated for European release this year, Epigenomics' assay won't be the first blood test–based colon cancer screen on the market; GeneNews beat them to the punch in 2008 with ColonSentry, based on microRNA expression.
Short, endogenous, regulatory RNAs that silence the translation of complementary mRNAs, microRNAs are relatively recent discoveries. Yet they have emerged as hot commodities in MDx, and Cepheid, Rosetta Genomics, Exiqon, and Combimatrix are all also pursuing them.
Exiqon's in-development assay for colorectal cancer prognosis is based on the detection of microRNAs with DNA analogs called Locked Nucleic Acids (LNA), because, says Søren Møller, Exiqon's vice president of research and development, standard nucleic acids just aren't specific enough.
"You don't have much sequence space," Møller explains. "microRNAs are 20–23 nucleotides long, and if you need to detect those in complex samples, you need very, very accurate detection techniques. LNA provides that advantage."
Rosetta's miRview squamous test uses RT-PCR of a single microRNA to help distinguish between squamous and nonsquamous NSCLC—an actionable result, says Tamir.
"Alimta is only labeled for nonsquamous NSCLC; Avastin is labeled for both," he says. But a "black box" warning on Avastin "warns against fatal hemorrhaging of 40 percent of the patients which are squamous."
A potentially life-saving decision based on a type of molecule researchers barely knew existed 10 years ago, it's just another example of putting the "personal" in personalized medicine. The MDx landscape continues to change as new technologies—like next-generation sequencing—come to the fore.
"There's a lot going on in this space, it's so exciting," says Glorikian. "Anybody who isn't in this space needs to ask themselves why."
Fred C. Tenover turned an early love of science into a successful microbiology career at the Centers for Disease Control and Prevention. He published 290 papers and became a noted specialist in drug resistant bacteria and moved into the private sector in 2008. Now 54, Dr. Tenover works at Cepheid, a molecular diagnostics company in Sunnyvale, Calif., where he's developing early warning tools to detect antibiotic resistant diseases.
Full name: Dr. Fred C. Tenover Age: 54 Hometown: Kalamazoo, Mich. Current position: Senior director, scientific affairs for Cepheid First job: Phlebotomist Favorite job: Current one Education: B.S. From University of Dayton; M.S. And Ph.D. From University of Rochester Years in the industry: 26 How I got to here in 10 words or less: I asked the right questions.
Q. You always had a love of science, but that wasn't what you planned to study when you arrived at college.
A. I had 16 years of Catholic education and had been interested in science since elementary school. So as a freshman in college, my intent was to go to the seminary and join a religious order where I could teach and still do scientific research.
Q. Did you ever have any problems reconciling those two halves of your life?
A. Not at all. I had read the work of a Jesuit priest named Pierre Teilhard de Chardin. He was also a serious scientist, a paleontologist, and the way he melded his science and faith became a model for me.
Q. But you ended up choosing science over theology. Why?
A. I did a three-month study tour at eight different universities throughout Europe and had a chance to talk to a lot of different people. That's when I decided science was more attractive to me than the theology side in terms of what I could do with my career. My faith still played a major role in my career.
Q. What did you plan to do once you actually decided to get a Ph.D?
A. I wanted to continue to do research particularly in antibiotic resistance, which was what much of my doctoral thesis focused on. I took a post doctoral fellowship at the University of Washington studying clinical microbiology in public health. I later became associate director of microbiology at the Seattle Veterans Administration. And I continued to teach at the University of Washington.
Q. Where did you go from there?
A. I was offered a job at the CDC in 1990 as the chief of the antibiotics investigation branch and later became director. It was an opportunity to focus on antimicrobial resistance and public health and lead a larger group of scientists. Plus, the CDC was the Mecca of infectious disease research.
Q. I understand you taught introductory microbiology to nonscience majors. Is there a secret to keeping nonscientists engaged when discussing technical topics?
A. Every lecture should have a lot of factual information and it should also be mildly entertaining. With infectious diseases as a topic, it's easy to get people to laugh in one moment and to scare the heck out of them the next. That's a great way to hold a group together, and you get great questions.
Q. What do you consider to be your most notable accomplishment while there?
A. One was the discovery of community MRSA [methicillin-resistant Staphylococcus aureus] in 1999. It's mostly spread person to person in hospitals by other patients or health-care workers that haven't washed their hands or worn their gloves.
Q. How did you discover it?
A. We saw a report of four kids from Minnesota and North Dakota, all from Indian reservations, that developed Staph. They were treated with antibiotics but died anyway. Shortly afterward, there were outbreaks in Pennsylvania, Mississippi, Georgia and Texas. This was a wake-up call since these are not strains of MRSA that leaked out (of a hospital). They developed in the community.
Q. One of your early investigations on MRSA involved professional football players. What did you find?
A. We investigated an outbreak with a professional football team in 2003. We found linemen had the most incidents of MRSA because -- we hypothesized -- they had the most skin-to-skin contact. I understand the early infections sidelined a few professional athletic careers including former Redskin defensive tackle Brandon Noble and college football player Ricky Lannetti. The CDC worked with the NFL and the NCAA to develop guidelines for wound management, prevention and care.
Q. Do you consider drug-resistant bacteria to be a bigger threat than flu?
A. Yes. There are more antibiotic resistant bacteria that threaten our health every day and will be for a long time to come.
Q. After years of public service, what prompted your move into the private sector?
A. I got a great job offer from Cepheid in 2008 to establish an external resource program with all of our customers, collecting organisms and characterizing them, looking for emerging resistance and changing strain types across the U.S. And internationally. It merges my love of microbial resistance and rapid diagnostics, something I saw the importance of when working in developing countries with the CDC and the World Health Organization.
Q. Was it a tough transition?
A. Not really, because I worked with a lot of diagnostic companies while at CDC. Helping them to improve products is something I already had in my portfolio.
Q. Your entire career has been dedicated to studying antimicrobial resistance. What's needed to control the problem?
A. We need better infection control, definitely need new antibiotics and new rapid diagnostics to find out where the patients are to find these infections.