19th-Century diagnostic methods make it too easy for “ESKAPE” pathogens to escape

  • December 1, 2018
  • All

In 2004, microbiologist Carl Nathan, M.D., wrote in a Nature commentary that:

"Treating infections with pathogen-specific rather than broad-spectrum antibiotics (whenever possible) will require prior, rapid, accurate and specific diagnosis. It makes no sense to use 21st-century technology to develop drugs targeted at specific infections whose diagnosis is delayed by 19th-century methods."1

In the decade and a half since Dr. Nathan wrote these words, the standard of care has remained mired in “19th-century methods.” Despite important diagnostic improvements made to post-blood culture methods, the days-long culturing of blood remains the foundation for pathogen-specific identification. Since clinicians cannot wait days to act when confronted with a patient suspected of sepsis, the standard of care remains empiric therapy. In the 2018 book, Superbugs: An Arms Race Against Bacteria, Lord Jim O'Neill and his coauthors describe the limitations of empiric therapy:

"Doctors usually treat patients using empirical diagnosis, which is little more than an educated guess based on a clinical assessment of the patient’s symptoms, history, and profile. This system is often not good enough to distinguish between bacterial and viral infections, or even to tell if the patient has an infection at all. If a bacterial infection is diagnosed, there is no way to determine if the bacteria are resistant or susceptible to standard treatments using empirical diagnosis since they produce identical symptoms, and our current diagnostic tests to distinguish between them take two days."2

Empiric therapy works for many patients, it has been demonstrated that approximately 60% of patients are on initial effective therapy, but there remain significant opportunities for improvement.3 A recent 1,400 patient, 11-site clinical trial led by investigators at UPMC found similar gaps: 2 in 3 patients were not on effective therapy at hour zero, and 1 in 5 patients were still on ineffective therapy 24 hours later.4

An Easy “ESKAPE”

Frighteningly, many patients who are not initially on effective therapy are battling a prevalent and deadly “ESKAPE” pathogens that cause the most worry for clinicians. The opportunistic ESKAPE pathogens were dubbed the acronym due to the bacterial pathogens being known for their ability to “escape” response to broad-spectrum antibiotics. The ESKAPE pathogens have been primary beneficiaries of “19th-century methods” of diagnosis. Of the six ESKAPE pathogens, four of the most common, E. faecium, S. aureus, K. pneumoniae, and P. aeruginosa, make up approximately 90% of all ESKAPE bloodstream infections.5  The Infectious Diseases Society of America (IDSA) elevated the profile of these pathogens with a report called “Bad Bugs, No Drugs” providing the ESKAPE name and highlighting the potential health crisis.6  Most of these pathogens are multidrug resistant and increasingly resistant to common empiric therapy such as the combination Vancomycin/Piperacillin-Tazobactam.

The 21st-Century Diagnostic for Fighting ESKAPE Pathogens

Enter the T2Bacteria Panel. The first and only FDA-cleared technology to detect prevalent and deadly ESKAPE pathogens in 3 to 5 hours – directly in whole blood! This breakthrough test is shown to provide results 2.5 days faster than the current standard of care.

Direct from whole blood technology is ushering in a new era of diagnostics, one befitting of 21st-century technology advantages described by Dr. Nathan in 2004.

Don’t wait another decade – it’s time to use 21st-century technology! Find out what it can do for you here.


1. Nathan, C. (2004). Antibiotics at the crossroads. Nature431(7011), 899.
2. Hall, W, et al. (2018) Superbugs: An Arms Race Against Bacteria. Cambridge, MA.; Harvard University Press
3. Buehler, SS, et al. Clinical microbiology reviews, (2016). 29(1), 59-103.
4. T2Bacteria Pivotal Clinical Study 2018. Manuscript under review.
5. Karlowsky, J. et al. Annals of Clinical Microbiology and Antimicrobials, (2004). 3:7.
6. Infectious Diseases Society of America. (2008, December 9). No ESKAPE! New Drugs Against MRSA, Other Superbugs Still Lacking. ScienceDaily.  

3 Lessons for Sepsis Committees with Dr. Sandy Estrada

  • November 15, 2018
  • All

The following is edited from a conversation with Sandy Estrada, Pharm.D., BCPS, Vice President, Medical Affairs, T2 Biosystems. Dr. Estrada was previously an Infectious Diseases Clinical Pharmacist for Lee Health in Ft. Myers, FL for 13 years where she served as the Co-Director of Antimicrobial Stewardship, Director of the ID Pharmacy Residency Program, and as a member of the sepsis committee.

Sepsis Committees Get It Right With Direct Patient Care Staff Involvement:

Sepsis committees often make a priority of identifying or hiring a sepsis coordinator. This position is typically held by a nurse or emergency department clinician. This leadership role for frontline caregivers helps center the committee’s actions on a passion for patient care and a desire to seek breakthroughs that can reduce sepsis mortality and improve patient outcomes.  

Integration with Existing Hospital Committees is Key:

Every sepsis committee should be conscious of other on-going committees and how to maximize its influence and expertise to drive improved patient care.  Many sepsis committees are relatively recent creations. At our hospital, the stewardship committee had been in existence for about a decade when the sepsis committee was first organized. The stewardship committee’s mission of fast and appropriate targeted antibiotic utilization is highly aligned with a core sepsis committee priority. In addition, many individuals were members of both the sepsis and the stewardship committees. Our sepsis committee was very successful when it leveraged and accelerated the work of existing committees, like stewardship.

You Must Get the Right Players at the Table:

An effective sepsis committee must be collaborative and have a balanced representation by clinical and administrative leaders. A purely clinical group is at risk of not having support from administration for proposed changes, while a purely administrative group may not have buy-in from the clinicians necessary to implement any changes. In addition, it is important to have someone from the IT department represented; they are key in making sure protocols and order sets get electronically implemented in a timely fashion.

“Killing the Kidneys” with Empiric Therapy?

  • October 17, 2018
  • All

A recent Pharmacy Practice News article ran with the jarring headline: “Killing the Kidneys to Save the Patient.”1 It drives at an issue facing many hospitals today: widespread use of antibiotics are at times negatively impacting kidney function – because hospitals have such limited data, they struggle to make timely appropriate antibiotic therapy choices. 

For millions of patients at risk of sepsis each year, the standard of care is to turn immediately to broad empiric antimicrobial therapy when a patient is suspected of a sepsis-related infection: dose patients with vancomycin and piperacillin-tazobactam, or a similarly broad-spectrum coverage. This is a pre-emptive strike while they wait for a diagnostic result that can identify the causative pathogen of the bloodstream infection – or if there is an infection at all. In fact, over 50% of the time, there is no infection at all! “Vanc” and “pip/tazo,” for example, are relatively cheap and effective – and necessary for a patient’s survival if they have a gram-positive infection like MRSA or a gram-negative bacteria like Pseudomonas aeruginosa or E. coli. When the mortality rate for sepsis rises ~8% each hour the patient goes untreated, the results of undertreatment are devastating.2 So this practice is the right thing to do, but it has consequences.

Kidneys are often paying the price. Broad-spectrum empiric therapy can cause nephrotoxicity or acute kidney injury in patients. Acute kidney injury causes excess waste products in blood and makes it challenging for kidneys to maintain the right balance of fluid in the body, and may negatively affect other organs. Some patients may be required to go on dialysis to help replace kidney function. A recent study demonstrated that vancomycin plus piperacillin-tazobactam increases the odds of acute kidney injury by threefold, and acute kidney injury increases hospital length of stay by approximately 3.5 days and costs by $7,500.3

Enter the heroes!
Every day, antimicrobial stewardship teams face pressure to safely de-escalate or discontinue broad-spectrum antibiotics when they are not needed. How can you convince clinicians that it is safe to change therapy without any diagnostics to guide the decision… because conventional blood culture results take days?

In part to reduce harm to the kidneys, hospitals and stewardship teams are turning to new, faster diagnostics like the FDA-cleared T2Bacteria® Panel. This test provides direct-from-whole-blood infection identification in 3 to 5 hours, without the wait of blood culture.

As described in a new white paper from Lee Health, T2Bacteria is a useful tool to support five antimicrobial stewardship goals including optimizing empiric therapy within hours.4 T2Bacteria research results demonstrate the panel can help rule out of P. aeruginosa and/or S. aureus within hours.

Don’t miss the two detailed case studies where therapy could have been narrowed and optimized days sooner, saving money and reducing the risk of adverse side effects – including the potential to reduce acute kidney injury.

1. Rosenthal, M. Pharmacy Practice News. July 2018.
2. Kumar, A, et al. Critical Care Medicine,(2006). 34(6), 1589-1596.
3. Luther, M, et al. Open Forum Infectious Diseases, Volume 3, Issue suppl_1, 1 December 2016, 1805, https://doi.org/10.1093/ofid/ofw172.1353
4. Weisz, EE, et al. Stewardship and the T2Bacteria® Panel: Early Research Experience at a Community Hospital. White Paper. September 2018.

World Sepsis Day: Sepsis survivors that inspired us this year

  • September 12, 2018
  • All

Welcome to the first ever T2Blog, an initiative that we take excitedly and seriously. We are excited to create a space where readers can keep up with T2. We are privileged to play a part in fighting sepsis with game-changing diagnostic technology that detects bloodstream infections and may prevent the progression to sepsis. Sepsis is a serious condition and we are serious about having a stake in the sepsis community. Throughout these blogs, we will address inspiring patient stories, challenges in sepsis management, T2’s technology, initiatives, and advancements in the field. So here goes! 

Day to day, it’s easy to get bogged down in the essential, but sometimes seemingly disconnected details of diagnostic tests: from reagent primers and probes to sensitivity calculations to getting the exact right amount of cells in a spiked blood sample. World Sepsis Day is an important reminder to step back and connect with the larger cause that fuels all these activities at T2: to save lives of patients with sepsis and help them return home to their families instead of the tragic, and often avoidable, alternative. This year, our team was fortunate to meet and support many strong sepsis survivors who have dedicated their lives to raising awareness by telling their personal stories in order to help others avoid the same tragic consequences. Their passion, commitment, and firsthand experience have helped fuel T2 during one of the most exciting and pivotal years in our company’s history.

In January, we met with Audrey Leishman via video and her husband, PGA Tour Professional Marc Leishman, to learn about Audrey’s battle with sepsis and her outstanding work with the Begin Again Foundation to support sepsis survivors get back on their feed.

Over the summer, Mary Millard visited our team in Lexington, Massachusetts to share her story. Mary is an inspiration with her willingness to share her personal story with such passion to improve care for similar patients. What could have been a routine cardiac procedure became a lifelong health battle after a bacterial infection was misdiagnosed and incorrectly treated for too long. Her story brings much-needed attention to the devastating health effects of sepsis and hospital-acquired infections. Mary gave permission to share her experience with sepsis – and the impact she could have had with earlier identification and treatment of the increasingly resistant Pseudomonas aeruginosa that forever changed her life.

We were inspired by the passion of the family of Emily Edwards, whose life was tragically cut short by sepsis. Her family is part of the National Family Council on Sepsis and hosted a Stepping Out Sepsis 5K in May in Dracut, Massachusetts. We were proud that team orange was there to support their important work!

This month, our team at T2 is again “Spiking Out Sepsis” on the front lawn at Hartwell Avenue with a volleyball tournament where the proceeds go to the Sepsis Alliance, an organization doing such valuable work to raise awareness.  

Thanks to all the individuals and organizations who are part of the fight against sepsis. Together, we can help eradicate preventable sepsis deaths!