<i>Clostridium Difficile</i>: Avoiding High-Risk Antibiotics


Following in-depth discussions regarding the risk for developing Clostridium difficile with the use of certain antibiotic therapies, Daniel E. Freedberg, MD, MS; Dale N. Gerding, MD; Yoav Golan, MD, MS; and Peter L. Salgo, MD, suggest how antimicrobial stewardship can improve patient outcomes.

Peter L. Salgo, MD: I don’t want to leave this topic without at least briefly visiting the topic of antibiotic stewardship in this country, and perhaps around the globe, and the overuse, perhaps the improper use, of antibiotics. How does that impact the incidence and severity of Clostridium difficile? My sense is that we’re seeing it more. I keep hearing we’re using more antibiotics in animal husbandry and whatever. Are they related? Are people getting too many antibiotics over the counter? Maybe not over the counter, but over the phone, if you will, or out in the community? Where does all this fit in?

Daniel E. Freedberg, MD, MS: I think the short answer is, yes. We’re using too many antibiotics; we should use fewer. And antibiotics do impact Clostridium difficile infection. And they seem to, interestingly, impact it at every level. So, if you look at hospitals that use a lot of antibiotics and compare them to hospitals that don’t use a lot of antibiotics, the ones that use a lot of antibiotics have a lot more Clostridium difficile—even after adjusting for other factors.

If you look at it at the ward level and adjust for all their factors, there’s going to be more Clostridium difficile in the ward that uses more antibiotics. We even looked at it at the individual-patient level. And if you look at patients in consecutive rooms, at patients coming into rooms, at the room level, the amount of antibiotics received by the room actually seems to impact the next patient’s risk for Clostridium difficile.

So, this has been likened to the inverse of “herd immunity.” Most people are familiar with this concept for vaccines, but this is kind of the downside to that. A lot of programs have been looked at to decrease rates of Clostridium difficile infection, and almost no matter how you try it, as long as you’re trying something, you can get your rates down. But the cornerstone of all these programs is antibiotic stewardship and using less antibiotics.

Peter L. Salgo, MD: And you can decrease the rate of antibiotic-resistant Clostridium difficile as well, where you don’t start selecting out bad Clostridium difficile?

Daniel E. Freedberg, MD, MS: There’s negligible vancomycin resistance to Clostridium difficile, as we talked about. It’s debatable whether there are some case reports of a higher MIC (minimum inhibitory concentration) to metronidazole with Clostridium difficile. So, it’s not so much antibiotic resistance that’s the problem. Rather, it’s that you created an environment where there’s just more Clostridium difficile around, more colonized patients, and patients shedding more clostridium difficile spores in their stools by using more antibiotics.

Peter L. Salgo, MD: Let’s talk about that.

Dale N. Gerding, MD: What you suggested has actually been done with clindamycin control. Some Clostridium difficiles have resistance to clindamycin. It’s the poster child for Clostridium difficile.

Peter L. Salgo, MD: I remember the introduction of clindamycin, and the first thing we heard was, “Clindamycin causes Clostridium difficile.”

Dale N. Gerding, MD: Well, it causes clindamycin colitis.

Peter L. Salgo, MD: Well, that’s not what we heard. And then we figured it out. But it was clindamycin Clostridium difficile—pseudomembranous colitis back to clindamycin.

Yoav Golan, MD, MS: But it’s not surprising that Clostridium difficile is such a big epidemic now because we live in an antibiotic-rich society.

Peter L. Salgo, MD: That’s my point.

Yoav Golan, MD, MS: The recent data suggest that 30% to 50% of antibiotic use is unnecessary. And the second component to that, by the way, that we shouldn’t forget is that when you use an antibiotic, don’t use it forever. Because much of the burden of antibiotics (the unnecessary use) is actually prolonging courses beyond what they really should be.

Peter L. Salgo, MD: All right. Let’s run through a few bullet points here before we leave. First of all, you mentioned fewer antibiotics, the antibiotics you use for shorter courses. Is that for all community physicians? Do you understand the position of a community physician who gets a call from a patient, a patient he knows or she knows well, who says, “I’ve got this, I want an antibiotic”? This community physician knows that if you don’t give the antibiotic, the patient is going to call somebody else.

Yoav Golan, MD, MS: So, one of the problems is in spending time with your patient and actually explaining that to the patient. But I think that if you do that and if the patient understands that they’re not going to benefit from an antibiotic, they’re not going to request it. If you decide to use an antibiotic, use the shortest effective dose—don’t use it forever. In the past, the thinking was that if you prolong the antibiotic, only good things can happen because it’s more of a good thing. But now we know that’s not necessarily the case.

Peter L. Salgo, MD: Are there some antibiotics, specifically, that you want to cut back on? If you talk to primary care physicians (the physician community in America), what antibiotics would you warn them to avoid, if at all possible?

Yoav Golan, MD, MS: It’s hard to avoid one class of antibiotics, and all antibiotics have some benefit. As we heard from Daniel and others, fluoroquinolones, ciprofloxacin, levofloxacin (some people call it “vitamin L,” as it became so prevalent in the community as well as in the hospitals), we know that these are among the highest risk factors for Clostridium difficile. And there are also, as we learned recently, risky antibiotics in terms of the heart and some other risks, such as the tendons and so forth.

Peter L. Salgo, MD: That’s with levofloxacin.

Yoav Golan, MD, MS: That’s with levofloxacin and moxifloxacin as well. So, avoiding the use of fluoroquinolones, when they’re not necessary or when you have an alternative that’s just as effective, where the patient could be treated effectively, would probably be your first step. Third-generation cephalosporins are also big risk factors, not that many are being used in the community. They are more so being used in the hospital. But this would be another risk group. Clindamycin—we already talked about. There are still some&mdash;mostly dentists, gynecologists, and obstetricians, at least from my experience&mdash;that use a lot of clindamycin. Well, we know that there are treatment alternatives that are less risky. That would be another route.

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