What if patients pushed for DNA sequencing in mystery infections? 💉🩸💬
There is a better way than bombarding a patient with antibiotics when the root cause is unknown, writes Dr. Eric Topol.
Many years ago, circa 2011, I had a hand infection. It started as nothing, the kind of kitchen mishap that normally would be long gone from my memory: I was struggling with the last bits of brownie stuck to a pan, and (not very smartly), using a knife to pry them off, when the knife slipped and went straight into my left palm.
It was a stab, enough to draw blood, but not worryingly deep. I cleaned it up, put on a bandage, and (more smartly) opted to soak the pan overnight.
But a few days later, the gash wasn’t healing. A week or two later, when we were visiting family, I noticed the hand was starting to swell and turning slightly purple.
Uh oh.
A wonderful cousin, who happened to be an ER physician, took one look at it and took me to the hospital.
It was an infection of some sort, but who knew exactly what?
I was admitted to the hospital, and the doctors began trying different antibiotics.
For a while, nothing seemed to be working. I remember one doctor coming in to tell me they were trying an antibiotic next called vancomycin, which I’d get through an IV.
What if that doesn’t work? I asked. Then what?
Vancomycin is a last-line antibiotic, he said, or something like that. It should work.
He said it so causally that somehow I didn’t worry. I didn’t wonder, what if it’s actually a different kind of infection, not a bacterial infection at all? What if I developed sepsis, a potentially fatal reaction to an untreated infection?
Along with the doctors, I waited to see what would happen.
Thankfully, my hand did start to get better. The vancomycin worked, and today, my left palm doesn’t even have a scar.
I thought of this hospitalization and my lucky outcome when I read a recent post by Dr. Eric Topol, a fantastic physician and researcher who writes a free newsletter called Ground Truths. (The Gold Foundation also awarded him the National Humanism in Medicine Medal last year. This newsletter is a side project and not connected to my job at the nonprofit Gold Foundation.)
In his post, “A Culture of [Blood Cultures]": Why hasn't rapid sequencing for serious infections and sepsis become standard of care?”, Dr. Topol details a method of revealing the “causative pathogen” through sequencing its DNA.
In other words, this method could have unlocked what microbe was causing my hand infection and allowed doctors to prescribe the best drug from the beginning.
Microbial DNA technology has been around for years, but it’s rarely used in urgent patient cases, Dr. Topol explained. In 2014, Dr. Sharon Peacock, a microbiology professor at University of Cambridge, pushed in Nature for sequencing of bacterial and viral DNA to be done swiftly in order to know what remedies will actually help a patient.
DNA sequencing has also been key recently in delivering critical information about a certain novel coronavirus, making it possible to develop a COVID-19 vaccine in record time.
But despite this amazing technology, if you or I were to have serious mystery infection today, the treatment path would likely be the same as it was for me a decade ago: a flood of antibiotic guesses.
Dr. Topol writes:
“Today when a patient presents with possible sepsis we draw multiple blood cultures and wait a few days before the results come back with a possible pathogen and readout for antibiotics that may be useful. The patient is bombarded with ‘empiric, broad spectrum antibiotics’ to cover all the bacteria that are thought to be potentially causal, with implicit acknowledgement that viruses and other pathogens (fungi, parasites) won’t be covered by the antibiotic cocktail. That ‘blitzkrieg’ cocktail, which may not even be directed to the underlying pathogen, has potential toxicity for the kidneys and other vital organs, and is typically continued until the cultures come back. All too often the cultures are negative, not revealing a/the pathogen, or show a contaminant, so, dependent on the patient’s clinical condition, the cocktail is continued for a full course of several days or longer. More potential for adverse effects of potentially misdirected antibiotics.
“In contrast, ‘clinical metagenomics’ as the field is known, takes an agnostic approach as to what is the causative pathogen. As shown in this excellent review, sequencing can be performed on any body fluid or tissue and there are several steps required, besides the sequencing, that include library preparation and bioinformatic analysis. There is no assumption about the bug—many cases successfully diagnosed by this technique would have been unthinkable pathogens, like an ameba or tuberculosis. The sequence tells the story in place of a clinician’s intuition for what might be the cause of infection.”
This missed opportunity is made all the worse because the other options — lots and lots and lots of antibiotics — is contributing to the growing resistance to antibiotics, which is incredibly scary and dangerous.
The obstacles to routine DNA sequencing include cost and expertise, but Dr. Topol points out that all of this is possible — the demand is just not there, because people don’t know about it.
Hence, that’s why I’m writing about this today. So that you know, and that you can push one day for this option, if you or a loved one is seriously sick with an unknown infection, or if you are a healthcare professional who might have sway on this in some way.
Here’s how Dr. Topol closes:
“The bottom line: this can be done, but we’re not doing it. There appears to be no drive or incentive to change or adopt this technology for routine medical practice. Meanwhile, sepsis is a leading cause of death—it accounts for 1 of 5 deaths globally—about 11 million deaths in 2017. Patients and their families don’t know about this technology, but if they did, and started clamoring about it, we might begin to see some traction. I keep thinking of how many lives we could save (and could have saved) if only we responded to the charge in Peacock’s 2014 editorial.”
Knowledge is power, my friends.
To our journeys,
Brianne
