Antibiotics Increase Risk of Older-Onset IBD

Use of antibiotics for gastrointestinal infections was associated with a greater risk for older-onset inflammatory bowel disease (IBD), a risk that was dose-dependent and persisted for years after an exposure, according to a population-based study presented at the Digestive Disease Week (DDW) annual meeting.

In this exclusive MedPage Today video, study author Adam Faye, MD, of the NYU Grossman School of Medicine in New York City, discusses the findings and its clinical takeaways.

Following is a transcript of his remarks:

This study was really looking at antibiotics as a risk factor for the development of older-onset inflammatory bowel disease ... comprising mainly of ulcerative colitis and Crohn's disease. And what we know is that antibiotics have been associated with the development of inflammatory bowel disease for all adults, and particularly the studies have really looked at younger adults. And there's been a bit of mixed results, but the majority have shown that there is an increased risk for Crohn's disease, with some also showing an increased risk for ulcerative colitis.

What we also know is that inflammatory bowel disease has a bimodal peak. So, not only are patients diagnosed early in life, but there's also another peak later in life. And these are patients typically 60 years and older. And when you look at the genetic risk and when you look at family history, it seems to be lower for older individuals as compared to younger individuals.

And so what that means is that likely the environment is playing more of a factor within these patients who have new-onset inflammatory bowel disease at 60 years and older. And so, because of all those things -- because antibiotics have been shown in younger individuals, because we think the environment may be playing a bit more of a role in older individuals -- we really wanted to basically take those two things and take a look at antibiotic use and see if it was a risk factor for the development of older-onset inflammatory bowel disease. And, really, there's not been much data looking at environmental factors at all in the development of older-onset IBD. So, this is kind of a new space to start investigating and will really help push us towards prediction and prevention.

The three things we really wanted to look at were, one, the number of courses of antibiotics in the years 1 to 5 prior to a diagnosis of inflammatory bowel disease. We wanted to look at the timing of antibiotic use. So, our hypothesis was, perhaps timing closer to the development of IBD, it's more of a trigger. And then the third thing we wanted to look at is specific antibiotic classes. So, are there specific classes that are more associated or less associated with the development of inflammatory bowel disease.

In speaking to the first, overall, any antibiotic use for an individual 60 years and older was associated with the development of inflammatory bowel disease. This held true for both Crohn's disease and ulcerative colitis in older adults. And when you actually look at increasing number of courses of antibiotics, what you see is that the risk increases with each subsequent antibiotic course used. So, this really points to a dose response. And so patients who had, or individuals who had, five or more courses of antibiotics in the last 1 to 5 years were at the highest risk of developing IBD. So, more courses of antibiotics, higher risk.

The second thing we wanted to look at was timing, and what we noticed that in the 1 to 2 years prior, there actually was a higher risk of developing inflammatory bowel disease. And the risk remained elevated, even when you look farther out, 2 t0 3, 3 to 4, and 4 to 5, but it actually was attenuated. We also looked at years 5 to 10, so did a bit of a sensitivity analysis even looking farther back. And antibiotics still were persistently shown to be associated with the development of inflammatory bowel disease in older adults. Again, the risk was a bit attenuated, but even antibiotics now 5 to 10 years back were associated.

And then the third thing we did was look at antibiotic classes. So when we look at the classes, the antibiotic classes that were associated with the highest risk are those that are targeting gastrointestinal pathogens. Those being the nitroimidazoles and the fluoroquinolones, and then the antibiotic class that was not associated with any risk of older-onset inflammatory bowel disease was nitrofurantoins, which is commonly used to treat urinary tract infections.

Our class of antibiotics called "other," which was a bit of an amalgam of a consortium of antibiotics that were less commonly used, so we couldn't power to look at them individually, also was not associated. But it's obviously harder to tease out because we can't look at those individual antibiotics. And when you look at the remainder of the classes, including narrow-spectrum penicillins, extended-spectrum penicillins, you see that the risk is still there. It's not as elevated as the nitroimidazoles or the fluoroquinolones, but it's persistently elevated in those groups.

So, all in all, I think this points to a couple of things. I think one takeaway is that we do need to be judicious in the use of our antibiotics. And we do see that antibiotics are associated with the development of older-onset IBD. We think judicious use of antibiotics is important for many reasons -- using them commonly can lead to multidrug-resistant organisms, but now we have another reason. And that's to prevent the development of IBD in older adults.

In patients who have more self-limiting courses, perhaps it's better if they're not indicated to hold off on empirically prescribing antibiotics and to wait until they're actually indicated, as opposed to a lot of times if someone comes in with a self-limiting illness, we expect them to get better -- a cold or things like that, we're just using antibiotics off the bat.

I think another thing to keep in mind is that antibiotics -- not just ones targeting gastrointestinal pathogens -- can impact the intestinal microbiome. So, that's our hypothesis is what we think going on is that the antibiotics are probably doing something to the intestinal microbiome. And that may be leading to the development of IBD in older adults. Obviously this needs to be looked at with further research, which I think is an important takeaway for clinicians and researchers that we will need to investigate.

And then another thing I think is important for clinicians is if you have patients who are older and they have ongoing gastrointestinal symptoms and they report frequent antibiotic usage or antibiotic usage within the past few years, perhaps this moves a little bit higher on your differential diagnosis when you start thinking about what perhaps is causing these gastrointestinal symptoms in older adults. There's a very long differential, so sometimes it can be very hard to figure out, is this truly inflammatory bowel disease or something else. And again, with that history of antibiotics, perhaps you're putting it a bit higher on your differential. You're thinking of other things like C. difficile infection, etc. But again, this starts to move up in my mind. So, I think those are the big takeaways for clinicians.

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