The toll of sepsis goes beyond the tragic consequences of patient mortality. Patients who survive sepsis often develop long-lasting effects like tissue damage, organ dysfunction or failure, and even loss of limbs. A study from the University of Michigan Health System, published in the JAMA medical journal in 2010, found that older severe sepsis survivors were at higher risk for long-term cognitive impairment and physical problems compared to similarly aged patients treated for other illnesses.
Considered together, these factors make sepsis the most expensive hospital-treated condition in the U.S., stretching resources thin with costs that exceed $20 billion every year. The question is: How can hospitals improve sepsis care while also reducing the associated costs of the illness? Fortunately, the answers work hand in hand.
The trouble with diagnosing sepsis
The biggest challenge for diagnosing sepsis is clear: time and accuracy of detection.
All diagnostics today require a blood culture. The problem is that by the time a patient shows sepsis symptoms, a physician draws blood, a lab runs the culture, and several days have passed. Initial blood cultures can take two to five days to show a positive finding, and then it takes anywhere from another two hours to three days for labs to determine the species of microbe causing the patient’s sepsis. Only then can physicians determine which drug to administer.
Sepsis patients – and the hospitals treating them – cannot afford this kind of waiting game. Worse yet is the guessing game: Blood cultures are only 50 to 60 percent sensitive. Physicians are often forced to hope for the best until subsequent testing and observation is completed.
The importance of accelerating detection
Like any illness, the sooner sepsis is treated, the better the patient outcome but the stakes for sepsis are substantially higher. In fact, every hour of delayed treatment increases mortality risk by nearly eight percent. This is why physicians typically try to buy time by putting patients on a broad spectrum of antimicrobial drugs (the guessing game again). Unfortunately, 20 to 30 percent of patients receive inadequate or inappropriate antimicrobial therapy for sepsis. This wide swath of drug therapies is also leading to an increased prevalence of “resistant” organisms as bacteria and other microbes adapt and become less responsive to treatment. In addition, the cost of treatment is increased as drug therapies are not specifically targeted at the pathogens causing the infection.
New technology can reduce sepsis detection time from 2-5 days to 3-5 hours
T2 Magnetic Resonance (T2MR®), a diagnostic detection method from T2 Biosystems, uses miniaturized magnetic resonance technology to measure how water molecules react in the presence of magnetic fields. T2MR can quickly and accurately identify sepsis pathogens direct from whole blood – without the need for a blood culture. It’s the first and only detection method to achieve this feat and dramatically reduces the time of detection by eliminating the 2-5 day blood culture process. It also increases sensitivity because there is no reliance on blood culture which suffers from a sensitivity of 50-60%. The first diagnostic panel to be developed using T2MR is for diagnosing Candida bloodstream infections.
The hidden dangers of Candida
While sepsis can be caused by a range of bacterial, fungal, or viral infections, Candida is by far the deadliest sepsis-causing pathogen. It’s the 4th-leading hospital-acquired bloodstream infection in the U.S. with over 100,000 cases every year – and a staggeringly high 40 percent mortality rate. Not to mention extensive hospital stays and extremely high costs per patient. Yet this danger often remains hidden, as 40 to 50 percent of Candida infections are missed by blood cultures.
This is where T2MR technology comes into play. The T2Candida® Panel is the first sepsis pathogen diagnostic panel that does not require blood culture and delivers species-specific results in just three to five hours – compared to up to six days with other diagnostics. Run on the fully-automated T2Dx® Instrument, the T2Candida Panel identifies the five clinically relevant species of Candida directly from whole blood. No other FDA-cleared Candida diagnostics technology can match its detection speed or accuracy. This improvement in speed can be potentially life-saving for infected patients.
The detection is in the details
If speed is the critical first step in sepsis pathogen detection, sensitivity and specificity immediately follow. The T2Candida Panel delivers a species-specific result in three to five hours while detecting very low levels of pathogen – as low as 1 CFU/mL, compared to the 100–1,000 CFU/mL required by PCR-based in vitro diagnostics. In the initial pivotal trial, T2Candida demonstrated a sensitivity of 91.1 percent and specificity of 99.4 percent. Most recently, in an analysis of 55 candidiasis cases, the T2Candida panel demonstrated 99.4 percent specificity and 96.4 percent sensitivity, according to study published in Future Microbiology.
T2MR enables these low limits of detection because it is not compromised or disrupted by a sample’s background – even the highly complex sample background present in blood from sepsis patients.
All other bloodstream diagnostic systems require sample purification and extraction, which can cause 90 percent of the target to be lost. It is also critical to remember that the target pathogens for these other diagnostic tests must be cultivated and amplified in a blood culture which has substantial limitations. Every blood culture test relies on something to grow, which not only takes time but also demonstrates only 50 to 60 percent sensitivity. As a result, both limit of detection and sensitivity are compromised for blood-culture-based diagnostic tests.
The benefits of speed and sensitivity are clear
For patients suspected of having sepsis and Candida infection, accelerated detection and a more accurate diagnosis can literally be a life saver. It means physicians can start administering appropriate treatment right away, helping to lower the risk of mortality while also reducing the chance of other long-term, detrimental effects of the illness.
For hospitals, improving the diagnosis and care of sepsis and Candidemic patients provides a strong return on investment for new technology platforms like T2MR. Because sepsis is such a costly illness, rapid detection provides significant length-of-stay savings. On average, Candidemic patients require 40 days of hospitalization, with costs that run upwards of $130,000. Patients who die cost 2.7 times more than patients who survive due to lengthy stays, extended time in the ICU and multiple interventions. A rapid diagnosis by T2MR can reduce this average cost by about $30,000 per patient.
The path toward saving lives and costs
A recent study showed that, in a 500-bed hospital with 5,100 annual high-risk patients, T2MR technology and the T2Candida Panel could save as much as $5,858,448 annually, due to decreased length-of-stay and reduced use of unnecessary antimicrobial drugs.
In addition, rapid sepsis detection reduced Candida-related deaths by 60.6 percent per hospital – or 31 lives saved over a year in that 500-bed hospital. This delivers an obvious boost in patient care while also creating a substantial increase in cost savings. After all, the last weeks of life are typically very costly, as patients move into the ICU and physicians attempt numerous interventions.
Next on the development roadmap for T2Biosystems is T2Bacteria, which when combined with T2Candida may enable 95% of sepsis patients to receive rapid and appropriate therapy on day zero.
The human body may always lead physicians down a trail of complexities and convolutions, but its reaction to infection no longer has to lead hospitals down a path of high costs and concerns.
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9 Pfeiffer, C. D., Samsa, G. P., Schell, W. A., et al. (2011). Quantitation of Candida CFU in initial positive blood cultures. Journal of clinical microbiology, 49(8), 2879-2883.
10 Mylonakis, E., Clancy, C. J., Ostrosky-Zeichner, L., et al. (2015). T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clinical Infectious Diseases, ciu959.
11 Mylonakis, E., Clancy, C.J., Ostrosky-Zeichner, L., et al. (2015). T2 Magnetic Resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clinical infectious diseases, 2015: ciu959.
12 Mylonakis, E., Clancy, C. J., Ostrosky-Zeichner, L., et al. (2015). T2 magnetic resonance assay for the rapid diagnosis of candidemia in whole blood: a clinical trial. Clinical Infectious Diseases, ciu959.
13 Pfaller, M.A, Wolk, D.M, Lowery, T.J. (2015). T2MR and T2Candida: novel technology for the rapid diagnosis of candidemia and invasive candidiasis. Future microbiology, doi:10.2217/fmb.15.111.
14 PLoS ONE | www.plosone.org | October 2010 | Volume 5 | Issue 10 | e13387
15 Pfeiffer, C. D., Samsa, G. P., Schell, W. A., et al. (2011). Quantitation of Candida CFU in initial positive blood cultures. Journal of clinical microbiology, 49(8), 2879-2883.
16 Bilir, S. P., Ferrufino, C. P., Pfaller, M. A., & Munakata, J. (2015). The economic impact of rapid Candida species identification by T2Candida among high-risk patients. Future microbiology, (10) 7,1133-1144.
17 Bilir, S. P., Ferrufino, C. P., Pfaller, M. A., & Munakata, J. (2015). The economic impact of rapid Candida species identification by T2Candida among high-risk patients. Future microbiology, (10) 7,1133-1144.
18 Bilir, S. P., Ferrufino, C. P., Pfaller, M. A., & Munakata, J. (2015). The economic impact of rapid Candida species identification by T2Candida among high-risk patients. Future microbiology, (10) 7,1133-1144.
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