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If pharmaceutical and biotech companies gave up trying to find better treatments for stroke and Alzheimer’s disease, there would be public outrage. Yet that is essentially what has happened to sepsis, an infection that kills as many Americans each year — about 250,000 — as stroke and Alzheimer’s combined — with barely a whimper. If we can strive to fight a new scourge like opioids, we should be able to do the same for a much older killer.

Thanks to antibiotics, vaccinations, and public health advances like modern sanitation, it’s easy to think that Americans live largely free of the infectious diseases that once took such a toll. That’s partially right: We effectively prevent many infectious disease threats. Cholera and typhoid, which once killed one percent of Americans each year, are now virtually unheard of in the U.S. Yet nearly 1.5 million Americans are hospitalized for sepsis each year, and it accounts for 1 in 3 deaths that occur in hospitals.


Sepsis is an old term. It may have been coined by Hippocrates more than 2,500 years ago. It is derived from the Greek word sipsi, meaning make rotten. In modern parlance, it is the syndrome of an acute, life-threatening failure of the body’s vital organs that develops as the body tries to fight off infection. It can start with something simple: an infected cut, the flu, a urinary tract infection, or many other seemingly benign afflictions. It is a case of friendly fire, where the body’s own immune system and other defense mechanisms respond clumsily to the infection, accidentally injuring or interfering with vital organs.

The best treatment for sepsis starts with rapid detection. The sooner it is diagnosed, the sooner doctors can start antibiotics and fluids in an effort to get the infection under control before the body’s immune system goes into overdrive. Patients require intense monitoring, as sepsis can take a turn for the worst in the blink of an eye.

Sepsis is the most expensive condition treated in U.S. hospitals, with many patients requiring prolonged care for multisystem organ failure in intensive care units. Researchers with the federal Healthcare Cost and Utilization Project found that sepsis, also called septicemia, cost $23.7 billion to treat in 2013.


Those who survive sepsis face an elevated risk of death for months or years; many end up back in the hospital. Recovery can be long and slow, and many individuals never return to work, living instead with both physical and mental disabilities.

Equally worrisome, the number of cases of sepsis is on the rise.

The onset of sepsis is pernicious. An individual can look relatively well until it is too late to intervene and stop the organ-destroying cascade of an overreactive immune system. That’s why there are efforts afoot to increase awareness and promote early recognition and treatment. Both Medicare and many state governments are driving initiatives to compel hospitals to have systems in place to ensure that every patient who might have sepsis is rapidly screened and started on resuscitation fluids and antibiotics.

The problem with these initiatives is that they begin and end with trying to make sure every patient can receive the best version of today’s care. It’s a noble and worthy goal, but it won’t on its own “solve sepsis.” If every patient with sepsis received the ideal current care, the mortality rate would drop a little, but 200,000 Americans would still die from it each year. We need a bolder plan to solve several problems in parallel.

First, we need better methods to identify sepsis early and accurately. There are plenty of potential inventions that could help, including smart wearable technologies that can detect physiological stress and decompensation and sophisticated molecular biology tests that can spot invading pathogens and the body’s immune response to them. Yet many of the companies developing these tools have neither the funds nor the wherewithal to test effectively and efficiently what can really help at the bedside.

Next, we need better treatments and strategies to care for patients, not just newer antibiotics. While there are potential therapies that might work, testing them in clinical trials is very costly. In addition, there aren’t really any incentives to entice the companies developing these drugs to work with those developing diagnostic technologies.

Finally, solving sepsis is not simply about avoiding death. We have to find better ways to help and treat sepsis survivors. The University of Pittsburgh Medical Center, where I work, Vanderbilt University Medical Center, and a few other hospitals have formed post-intensive-care recovery clinics for sepsis survivors, among other conditions, but most patients live far from any organized and focused support. And there are few programmatic research programs testing strategies to improve long-term outcomes from sepsis.

Many of the tools that might be useful to truly reduce sepsis exist but are scattered across hospital and research institutions. There is no coordinated effort to bring together researchers, industry, hospitals, and patients.

The government, through agencies such as the National Institutes of Health, has consistently supported individual research projects related to sepsis. But the NIH should be working with academic researchers, clinicians, and the private sector to do more. The government, in particular, could serve as a catalyst and coordinator-in-chief by taking a page from former Vice President Joe Biden and calling for a moonshot for sepsis. The term may be overused, but the concept is exactly what we need.

Sepsis is the most expensive and deadliest condition we are battling in our hospitals. But when did you last see headlines trumpeting a blockbuster new sepsis drug? You haven’t — and you won’t — until we make a serious commitment to fight the oldest disease of all.

Derek C. Angus, M.D., is professor and chair of critical care medicine and director of the Clinical Research, Investigation, and Systems Modeling of Acute Illnesses Center at the University of Pittsburgh School of Medicine. He reports receiving grant support from the NIH and consulting fees from Bayer, Beckman Coulter, Biocartis, Bristol-Myers Squibb, Ferring, GenMark, GSK, and Sobi.

  • Thankyou Dr. Angus for this courageous exposure of the limitations of standard sepsis science.

    As you know, sepsis science is a 30yr aberration of political expediency wherein consensus has replaced discovery. As Popper feared, young sepsis scientists are taught the standards guessed by their mentors when their mentors were young. Using these guesses as standards, there have been no reproducible positive sepsis randomized controlled trials for 30 yrs. and mortality varies in the control groups across trials by nearly 500%.

    The research standards “Sepsis 1,2,& 3” (SIRS and SOFA), were guessed in the 1990s. Their mandated by grant reviewers use has doomed the science to a state of perpetual nonreproducibly.

    No science can prosper using guessed, one-size-fits-all standards for clinical research. It is not surprising that sepsis research, hobbled in this way, have failed to generate reproducible positive results for nearly 30 yrs.

    We are still waiting for one of the sepsis thought leaders to gain the courage to admit publically that the emperor has no clothes.

    This editorial is a good start but this is usually where the thought leaders end their public discourse. The next step, admitting that the past approach was wrong and calling for release of the science from these false and failed standards must he publically disclosed by sepsis thought leaders.

    The logical and pivotal step after a paper saying “it’s not working” is to publically discuss the potential reasons for that failure.

    Until that deep, courageous introspection paper is published by the thought leaders and they release the young scientists with grants to seek their own course of discovery, free of the false standards, real progress cannot be expected.

  • Its truly heartbreaking that Sepsis remains the third leading cause of death when a cure was announced a year ago. The Marik Protocol represents a real breakthrough, offering safe, effective, affordable adjunct therapy for Sepsis with a remarkable reduction in Death rate. So why the widespread skepticism, reluctance to implement this therapy on a trial basis ? Besides the wide spread bias in the Medical Community favoring prescription drug therapy ( this therapy relies on natural metabolites ), there is the money involved in treating Sepsis. Sepsis patients represent a group that stays in the Hospital longer, and with more repeat visits. Hospital administrators make more money off of Sepsis patients, and have little to gain by a therapy that sends patients home quickly, having attained a more robust recovery. Organizations like Sepsis Alliance, which has a critical view of the Marik Protocol likewise have everything to loose from an affordable cure. They never reveal their conflicts of interest when they offer their critical opinions.

    Meanwhile, patients are not offered a choice of treatments, and death by Septic Shock remains a leading killer, with 8 million people die yearly world wide, a genocidal rate of mortality considering a cure is being ignored.
    Need Convincing ? Listen to what the ICU nurses who have witness the healing of the Marik Protocol have to say: ICU nurses discuss vitamin C therapy for sepsis

    See Cost of Sepsis:, see Scepticaemia: The impact on the health system and patients of delaying new treatments with uncertain evidence; a case study of the sepsis bundle [version 1; referees: 1 approved] ,,

    I have no conflicts of interest in this issue.

  • Why haven’t we seen headlines trumpeting a new sepsis drug? We have seen these headlines. It’s a hydrocortisone-vitamin C combination advocated by Dr. Paul Marik. It’s under test right now. If it cost $40,000 per patient instead of being cheaper than current treatments, it would be used everywhere by now. The lack of a corporate sponsor slowed it down. Still, 10%-15% of ICU’s are using it. If you want a bold approach, don’t wait for studies, but instead start using it on 50% of your patients immediately, and see for yourself whether it helps.

  • How about if you lobby to lengthen the exclusivity for new antibiotics and antifungals? The tools you want are all about spending money. How about changing the incentives for the Biotech industry?

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