For the unfortunate few who become infected by clostridioides difficile (c diff) the initial and hopefully, final treatment is an antibiotic. But, wait! Aren’t antibiotics part of the problem? Don’t people GET c diff after taking antibiotics? Well, yes. When antibiotics impair your gut microbiome by killing off both good and bad bacteria, it can make it easy for c diff to take over. C diff is treated with a few specific antibiotics including oral vancomycin and fidaxomycin (Dificid©) and sometimes, metronidazole. These antibiotics are specifically active against c diff in part because they accumulate in the colon where c diff resides.
Don’t all antibiotics work against an infection?
No, as mentioned in a previous post, antibiotics are not a one-size-fits-all solution. A given antibiotic works against a few different strains of bacteria. That is why a prescriber needs to carefully consider what they are treating. Bacteria tend to preferentially affect different tissues, for example, one bacteria may tend to cause pneumonia in the lungs, while another causes urinary tract infection in the bladder. Also, antibiotics tend to penetrate different tissues differently. In urology, I used specific antibiotics that targeted the bladder or prostate and the bacteria that affected them specifically. I prescribed antibiotics that saturated the desired tissue, for example, the prostate, better than other antibiotics would have.
So what antibiotics are used to treat c diff?
C diff is treated with oral (not intravenous) vancomycin or oral fidaxomycin because when taken by mouth, these antibiotics don’t go into the bloodstream but are excreted in the gut. This means they are found in concentration in the colon where the bacteria are hanging out. They work right where they are needed. Metronidazole is also used in children and low-risk patients (younger, healthier), but it is not as effective.
But don’t antibiotics damage the microbiome?
Well, yes. That is the trade-off. The problem is that c diff makes toxins that damage the colon lining. These toxins inhibit the growth of good bacteria, to keep them away so c diff can flourish. (Sneaky buggers, bacteria and viruses – they are all about living and reproducing. Kind of like people.) Antibiotics that kill off c diff also kill off some of the good bacteria. This makes it harder to restore a more normal microbiome, which in turn inhibits c diff growth. Unfortunately, antibiotics have no effect on the bacterial spores. So after killing off the live bacteria, with the microbiome damaged by the antibiotic as well as the c diff infection, those persistent c diff spores blossom into bacteria again and the infection recurs. See a cycle here? Recurrence occurs at least once in about 25% of people who have c diff.
How are the antibiotics for c diff taken?
Vancomycin is one of the first-line choices to treat c diff. Like other antibiotics, it can damage the microbiome, and it is associated with recurrence of infection. For an initial infection it is take 4 times daily for 10 days. For recurrent infection, it is taken either as a 14 day course or in an extended taper lasting 6-12 weeks or longer. To take a tapered course, you’d start it 4 times a day and taper down to every other day for a few weeks. Some patients take it indefinitely over time. It costs around $1,000 for a long tapered course, but it is covered by most insurances. (As an aside, intravenous vancomycin is used to treat MRSA, a drug-resistant staph infection that affects skin and soft tissues. In its intravenous form, it is in the blood stream which helps it saturate the skin and soft tissues where staph causes infection.)
Fidaxomycin is a newer antibiotic that treats c difficile. It also impairs the microbiome, but less so than other antibiotics. There is significantly less recurrence with it compared to vancomycin. For this reason, last year guidelines for the treatment of c diff were updated (see link below), with a caveat. It is now a first-line choice, given the increased cost. Even though it costs more than vancomycin, it is thought to be cost-effective by preventing more recurrence. A ten-day course of fidaxomycin costs about $5,000 out of pocket. If you are privately insured, you can go to the Merck website and get a co-pay card for as little as $50 for a course. It is typically taken twice daily for 10 days.
Metronidazole, along with vancomycin, was historically used as first-line treatment. However more recent studies showed it was inferior to vancomycin in achieving initial cure. It is now the second-line choice, behind fidaxomycin and vancomycin for treatment of adults. For children, however, it works well when used for mild infection.
How effective are these antibiotics?
Well, recurrence does occur in about 25% of people who have an initial c diff infection. Of those, another 40% go on to have a third infection, then the risk is over 60% for a fourth infection. I belong to a support group at the Peggy Lillis Foundation. I have heard of recurrences after taking all three antibiotics to treat c diff. However, anecdotally I’d say there seem to be more recurrences after taking vancomycin than fidaxomycin. I myself have failed vancomycin 4 times. I have not taken fidaxomycin, but have been in remission since having a fecal microbiome transplant. After my last recurrence, I also had an infusion of a monoclonal antibody called bezlotoxumab (Zinplava©).
What is a monoclonal antibody?
Simply put, it is a laboratory-made antibody. You’ve heard of monoclonal antibodies for COVID- they attach to the virus to inactivate it. This one, bezlotoxumab, is an antibody that attaches to one the toxins produced by c diff, toxin B. Because toxins A and B damage the lining of the colon, they facilitate ongoing infection and increase the risk of recurrence. The damage to the cells lining the colon, called enterocytes, allows bezlotoxumab to pass from the bloodstream into the colon where it binds toxin B. This allows the gut to heal over the following 12 weeks. It is taken while taking antibiotics to kill off the bacteria. I am grateful that I was able to receive it. And between that, the antibiotic and fecal microbiome transplant, I am free of infection. Whew! That was a lot of work.
New treatments are coming…
Several companies are looking at restoring the gut microbiome as the key to breaking the cycle of c diff infection recurrence. Some new products are in stage three clinical trials now, meaning there will be new treatments brought to market in the next few years.
What’s next? Let’s talk about your microbiome, what it does, in a bit more depth. I have a neat video you can watch and we’ll review some new data about the other things your microbiome is associated with, like your mood and cognition. Oh, and how to rebuild it!
you explain it so well. Much appreciated!