What microbes cause sepsis?

Sepsis can arise from all sorts of illnesses, but what about the microorganisms themselves that cause the initial infection? Eva Higginbotham spoke to Andrew Conway Morris, an intensive care doctor specialising in sepsis at the University of Cambridge...

Andrew - You can get sepsis from bacteria, you can get sepsis from viruses. You can get sepsis from fungal organisms. And so really across the range, and equally some parasites, such as malaria in the severe forms, would also meet our definitions of sepsis. In terms of the common organisms that we see, the most common are certainly bacteria. And again, they come from a range of different types of bacteria. If we split bacteria, broadly speaking, into gram-negative and gram-positive, which is how they stain under a microscope, we see common gram-positive organisms, such as staphylococcus aureus, and many of your listeners may have heard of MRSA. Other common organisms would be E. coli and pseudomonas. And these are organisms that often we get from the gut or from the urinary tract. So it's a pretty broad field of organisms. And it's a very interesting question as to why you get the sepsis syndrome, how much of that is due to the bug and how much of that is due to the host response

Eva - And what is it that the host is responding to when they have an infection with something like e. coli?

Andrew - So the surface of the microbes, the bacteria and so forth, are covered in molecules. And what the body does, the immune system is able to recognise those patterns and says, this is an abnormal thing that shouldn't be here, and therefore I'm going to launch an attack because it shouldn't be here and it needs to go. Now, the key thing with sepsis is that that response is not localised to a specific area, but rather spills out into the rest of the body. And again, why that happens is one of the key questions of sepsis and one that we don't fully understand. There is almost certainly an interaction there between the bacteria and the host immune system. And some of that will be dictated by the host's own genetic background. Some of it may also be due to the experience of the immune system, whether they've encountered that bug before and also where in the body it's encountered. So e. coli one commonly has in one's gut. They live there without causing any harm most of the time, but if they spill out of the gut and they get into say, for instance, your abdominal cavity, to the space around the gut, or they get into your bloodstream, then your body mounts a very vigorous response to that, and that is probably what triggers sepsis.

Eva - And does the bacteria, or other infective organism, want this to happen? Like, is it in the gut trying to burrow through with some tools it might have in its toolkit? Or is that not exactly what it wants?

Andrew - There are clearly examples of organisms that have what we call invasive potential, who you get enteroinvasive e. coli, so that's e. coli that would invade through the wall of the bowel, or you get invasive streptococcal disease where you have a streptococcus pneumoniae, so causing pneumonia, and that spreads into the bloodstream, or sometimes into the central nervous system causing a meningitis as well as a pneumonia. And some of that will be due to virulence factors carried by those bacteria that have the potential for invasion. But some of it again is probably also down to the host response. If the area where the bacteria are becomes leaky and your barrier defenses break down, then that again, allows those bacteria that have the potential to cross, to cross into areas where they shouldn't be.

Eva - Can you always figure out, when you're treating someone for sepsis, what the microorganism was that caused the reaction?

Andrew - So, no, and in fact, it's very common, probably in around 50 to 60% of cases of infection that present to hospital we can't identify the infecting organism. In a relatively small proportion that will be because we got the diagnosis wrong, but most of the time it's because our tests for infecting microorganisms are just not very good. They are based on technology developed originally by pioneers, such as Louis Pastor, over a hundred years ago. And they rely on the growth of bacteria. And in order for the bacteria to grow, they need to be in the right conditions. And also the patient needs to have not been given antibiotics that suppress the growth of bacteria, and of course you must give antibiotics early. And so it is very common not to be able to identify the infecting organism. This is changing, technology is coming that allows us to identify organisms without relying on growth. So we can use molecular tests, things like PCR, polymerase chain reactions, which allow you to detect genetic material and doesn't rely on growth, but those tests are not yet widely available for bacteria. They're widely implemented for viruses, and that's exactly what we used for respiratory viruses like SARS-COV-2, to the cause of COVID. But for bacteria, they're not that well developed and we're forced to rely on broad spectrum, empiric antibiotics - so antibiotics that we pick because they're likely to cover the organisms we think will be there. And clearly that comes with risks of breeding resistance, of using antibiotics with a broader spectrum then we need to, possibly for longer than we need to. And there really is an urgent need for diagnostics in this area to allow us to rationalise our antibiotic therapy, to minimise the use of antibiotics and preserve them because they're a precious resource