Though it may eventually be eclipsed by the emerging multidrug-resistant gram-negative pathogens, Clostridium difficile is, for all intents and purposes, the tyrant king of healthcare infections.
It’s close to a literal gut punch, typically setting up as an enteric infection after healthy, commensal bacteria have been blasted away by indiscriminate broad-spectrum antibiotic use. In particular, the NAP1/027 C. diff strain is highly virulent and toxigenic, causing a miserable panoply of symptoms from recurrent diarrhea to life-threatening breakdown of the colon.
“The most common bug acquired in the hospital, C. diff kills 15,000 to 30,000 people every year and costs more than $4.8 billion a year in hospitalizations alone,” according to new guidelines issued by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.1
With input from the CDC, the IDSA and SHEA guidelines recommend fecal transplant for recurrent cases, outline new testing strategies, and recommend new first-line antibiotics. Updating the 2010 guidelines, the recommendations still emphasize glove use as the most important infection control measure, as hand-washing with alcohol and even soap may not eliminate C. diff spores from hands.
L. Clifford McDonald, MD, co-chair of the IDSA/SHEA C. diff guidelines panel, is the associate director for science in the CDC Division of Healthcare Quality Promotion. Hospital Infection Control and Prevention asked him to comment on some of the recommendations in the following interview.
HIC: C. diff has been recognized as a major threat to patient safety for several years now. Have you been able to make much progress in reducing it and is the NAP1/027 strain still causing the majority of severe infections?
McDonald: We have seen some decline, but not nearly what we want to see. The standard infection ratio for the hospital-onset infections is surveyed in [the CDC’s] NHSN. That came down 8% by 2014, and from 2015 to 2016 there was another 8% decline.
You could say that maybe we are at a 15% to 20% decline, but we really wanted to see at least a 30% decline at this point. So, we are not moving as dramatically as we should. The 027 strain is the main source we see in our Emerging Infections Program — 10 sites across the U.S. with 14 million people under surveillance. The 027 is the most common strain for healthcare settings, which includes hospital-onset disease.
HIC: Antibiotic stewardship has certainly been heavily emphasized of late. Are you seeing any signs that more prudent use of antibiotics is having an impact?
McDonald: When you sort it out by comparing our antibiotic use measures to England, for example, we are still using a lot of fluoroquinolones. [Reductions might be critical] for this 027 strain in particular because it is fluoroquinolone-resistant. But we know that the cephalosporins are also bad characters.
We have not seen antibiotic stewardship linked to reductions in a big way, and part of that is because we are starting out behind the 8 ball with a lot of antibiotic use. That said, there have been hospitals that have reduced specific antibiotics and have seen declines in their C. diff rates. We are doing some of that analysis now, but it is not out yet. There are hospitals that reduced their fluoroquinolone use and others that have reduced their cephalosporin use, and that has been associated with declines. So, it does work, but we need to see much more.
HIC: The C. diff guidelines recommend testing patients with new onset of unexplained diarrhea, defined as three or more unformed stools in 24 hours. It is also noted that molecular tests are used in more than 70% of hospital labs, but these tests have pros and cons.
McDonald: We didn’t come out in this guideline and talk about “diagnostic stewardship,” but I think that is something you will hear more about. The WHO is using that term. With any test for any condition, the results always have to be considered in the context of the patient tested. Any test will suffer if you order it for the wrong patients.
In the case of the nucleic acid application test — the PCRs — they are very sensitive. They are great for ruling out disease. But if they are positive, it does seem that patients can have diarrhea for other causes. In fact, one study found that 19% of patients who were getting a C. diff test ordered were on laxatives. So that kind of thing — not paying attention — [is a problem]. In looking at the criteria for ordering a test, it is three unformed stools of diarrhea which is unexplained. If someone is on a laxative that causes diarrhea, ordering a C. diff test is circumspect.
HIC: There is a new recommendation for fecal microbiota transplantation, the transfer of healthy stool from a donor in an attempt to restore healthy gut bacteria and eradicate C. diff in the recipient.
McDonald: We recommend it for patients with multiple recurrent C. diff, so that is new. It is for patients with multiple recurrent C. diff who have failed appropriate antibiotic therapy. That is “appropriate” antibiotic therapy, and we lay out some new recommendations for treating primary C. diff and recurrences.
HIC: Yes, the guidelines include new recommendations for treatment, including dropping metronidazole as a first-line drug in favor of oral vancomycin or fidaxomicin.
McDonald: Another big change in this guideline is that we have moved metronidazole to no longer recommended as a first-line therapy. Metronidazole can be used if oral vancomycin or fidaxomicin are not available, but those other two agents are the recognized first-line therapy.
Recurrence of C. diff is a big problem. About 20% of patients who are adequately treated for primary C. diff will go on to develop a recurrent infection. A good take-home message is after the first recurrence, do something different. If they received metronidazole for some reason as the first-line drug, don’t use that again. If they had oral vancomycin for 10 days — which is the recommended time — then try to taper it down or try fidaxomicin. We offer some things to try, so we put out more recommendations dealing with recurrence, which include finally FMT for multiple recurrence in patients who have failed appropriate therapy with antibiotics. [FMT] is a new general area along with the diagnostics — those are the two big areas of change.
HIC: The role of probiotics in controlling C. diff remains unresolved in these new guidelines.
McDonald: We don’t recommend against it, but we say there is insufficient data to make a recommendation. I think it is worth noting, because certainly there have been several meta-analyses that suggest there is a role for probiotics in preventing C. diff.
We are not necessarily denying that. A recent Cochrane Review recommends this, but we are stuck with the fact that there is no single probiotic formulation that has been studied sufficiently to make a guideline recommendation to “use this probiotic in this dose for this period of time in these patients to prevent C. diff.” That’s what you need to make that kind of recommendation.
Lack of Options
HIC: But you decided there was enough evidence to recommend fecal transplant?
McDonald: Part of it is the [limited] number of options available. Probiotics would be for prevention, and we know a lot of other ways to prevent C. diff, like antibiotic stewardship. When you get a patient with multiple recurrences who has failed antibiotics, there are not many options. [FMT] has been shown to help a lot of people. A couple of randomized control trials suggest it does work. A lot of patients have received it, and so far, there has not been a safety concern.
But at the same time we know that it is not a standardized product, obviously. Human stool used for this purpose is considered a drug by the FDA. They have made that clear, so normally this use would require an investigational new drug [approval], but they have agreed to apply enforcement discretion, meaning for this particular reason it can be used. That’s why we felt like we could recommend it for a subset of patients who fail everything else.
HIC: In terms of infection control, is there still an emphasis on glove use due to the historical problem of removing spores from hands?
McDonald: This does include infection control, but there are not a lot of changes there. We do recommend extension of C. diff isolation to 48 hours after resolution of diarrhea. That was in the SHEA isolation guideline. There is an emphasis on gloving.
All our infection control guidance is focused on infection control of symptomatic C. diff patients diagnosed with disease. We do talk about asymptomatic carriers but we don’t have any recommendations in that area. It is an area of active research. For the patients with symptomatic C. diff, gloves are first and foremost. That is clear. The question then becomes: How do you do hand hygiene upon glove removal?
HIC: That raises some issues we have certainly discussed in the past about hand hygiene and C. diff.
McDonald: There is a theoretical benefit for soap and water over alcohol-based hand sanitizers. Alcohol does nothing to C. diff spores — we know that. With that said, it is not just C. diff we are concerned about. We are worrying about any kind of organism that can affect the patient. There are many other threats out there that are more effectively killed with alcohol than soap and water. Then you look at some of these studies of [the difficulty] of getting the spores off the hands even using soap and water, and you realize gloves are first and foremost. Soap and water can also have problems with compliance. In this guideline, we say perform hand hygiene after glove removal with either soap and water or alcohol-based hand rubs. Then we have another recommendation that if you have sustained high rates or an outbreak, then use preferentially soap and water. It is a theoretical benefit, but has never been shown in and of itself to reduce C. diff transmission.
- McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) [published online February 15, 2018]. Clin Infect Dis doi: 10.1093/cid/cix1085.