COMMENTARY

New Help for Managing Clostridium difficile Infection

Revised IDSA/SHEA Clinical Practice Guidelines

David A. Johnson, MD

Disclosures

April 26, 2018

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

Clostridium difficile infection (CDI) is not an uncommon thought in any inpatient or outpatient provider's mind. The American College of Gastroenterology (ACG), under the excellent leadership of Dr Chris Surawicz and Dr Larry Brandt, issued a guideline in 2013 that was extremely helpful in providing evidence-based recommendations for clinicians dealing with CDI.[1] The Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) recently issued new clinical practice guidelines for CDI.[2] I am going to [compare and] contrast the two guidelines and tell you what I learned from reviewing them so that you can apply this guidance to your practice.

Clostridium difficile Is an Increasing Problem

CDI is increasing at an alarming rate. There are nearly 500,000 cases per year in the United States.[2] The proportion of discharged patients diagnosed with C difficile has more than doubled over the past 9 years.[3] There are also increased hospital lengths of stay—nearly 5 days more when CDI is diagnosed.[3] The cost for that extended timeframe is an extra $15,000.[3] Healthcare-acquired CDI has also doubled from 11% to over 22% over the past several years.[3]

Furthermore, under the inpatient prospective payment system, the Centers for Medicare & Medicaid Services added CDI to a penalty rate in 2017. If a patient is readmitted within 30 days after CDI, there is no payment for that hospital stay. The estimated cost is around $15,000-$17,000. So, there are huge implications for cost. Billions of dollars are involved for prevention of CDI recurrence as it relates to repeat hospitalization.

Testing

Let's talk about the new guidelines.[2]

The first recommendation is not to test if there is no diarrhea. This is inordinately apparent in our hospital. We cannot get the test run by the lab unless there is diarrhea.

The test is best performed using a toxin plus glutamate dehydrogenase, an antigen present in virtually all strains of C difficile, toxigenic and non-toxigenic. This is then amplified by a test for the specific gene itself by a toxin immunoassay or a nucleic amplification assay. Your lab is doing this—it's just important to recognize that that is the standard.

Do not repeat testing within 7 days during the same episode of diarrhea.

Do not test stool from asymptomatic persons, except if you are doing some type of epidemiologic study. This is important because I'm aware of some hospitals that are trying to pretest people prior to admission, and there is not sufficient evidence to recommend that at present. Recognize that 1%-3% of the adult population are asymptomatic carriers, and it is much more prevalent at medical facilities like nursing homes and extended care facilities.

There is an incredibly high prevalence of asymptomatic carriage in infants. There is a very strong recommendation from the new guideline that if you do treat infants, the asymptomatic carriage is so high that you should not even screen for C difficile in neonates or infants aged younger than 12 months. In that population, do not even test.

In the 1- to 2-year-old age group, there is still a high prevalence [of asymptomatic carriage] and they should not be routinely tested. If all other causes of diarrhea have been excluded, then consider testing for C difficile.

For those older than 2 years, test if there is a concern and as directed.

Infection Control

The new guideline states that handwashing with soap and water is better than disinfection with alcohol-type products. This helps remove the spores. Soap and water before and after [caring for a patient] is the recommendation.

Again, should we test for asymptomatic carriers? There is no recommendation for this, so we should not be doing it routinely. Studies have looked at this upon entry into the hospital. This is somewhat problematic from a stratification bias, so the recommendation is that there is no official policy.

Antibiotic Stewardship

We are seeing tremendous emphasis on antibiotic stewardship across the board in a variety of different disease states.

Antibiotics should be targeted on the basis of the local epidemiology of your C difficile strains at present, if they are known. Fluoroquinolones (which seem to be doled out like candy), clindamycin, and cephalosporins (except for surgical antibiotic prophylaxis) should be restricted.

There is a strong recommendation to be better antibiotic stewards.

Preventive Antibiotics

What about preventive antibiotics for patients admitted with a prior history of CDI? There are no good data on this. If the patient is at particularly high risk, a soft recommendation is that antibiotics could be considered but perhaps at a lower dose (eg, vancomycin 125 mg/day or fidaxomicin at 200 mg/day for 10-14 days). Again, there is no official recommendation but some hospitals do this.

Proton Pump Inhibitors

Proton pump inhibitors (PPIs) take lots of heat.

This guideline says that although there is an epidemiologic association between PPIs [and CDI], the evidence suggests that PPIs do not need to be discontinued to prevent CDI. They should be continued and discontinued as appropriate.

First-Line Treatment

The new guidelines recommend vancomycin 125 mg four times a day or fidaxomicin 200 mg twice daily for 10 days as first-line treatment.[2] This differs from the ACG guideline, where metronidazole is recommended for mild to moderate infection.[1]

Also, highlighted in the ACG guideline[1] from 2013 is that vancomycin can be given as a compounded medication. Get your pharmacy to compound vancomycin using the intravenous formulation rather than the commercially available encapsulated vancomycin. The cost savings is considerable; it is 10-15 times cheaper by using a compounding pharmacy.

If you do not have availability of vancomycin or fidaxomicin, the new guideline[2] recommends metronidazole 500 mg three times a day for 10 days. Repeated or prolonged courses with metronidazole are not recommended because of the risk for irreversible neurotoxicity.

Fulminant C difficile

What about fulminant C difficile? The new guideline recommends oral vancomycin 500 mg four times a day.

For patients with ileus, the recommendation is to give oral vancomycin 500 mg four times a day, vancomycin 500 mg in approximately 100 cc of normal saline every 6 hours as a retention enema, and metronidazole 500 mg intravenously every 8 hours.

Recurrence

Recurrence is a real problem. The recurrence rate after a one-time episode of CDI is approximately 15%, typically within the first 3 months. [After one] recurrence, the rate of recurrence seems to compound very quickly, going up to [40%-65%].[1]

The new recommendation is to give oral vancomycin for the first recurrence of CDI using a tapered and pulsed regimen.[2] The pulse recommendation is somewhat soft. The ACG guideline[1] proposed a regimen of vancomycin 125 mg four times a day [for 10 days] followed by 125 mg pulsed every third day for 10 doses. The current guideline[2] recommends that after the usual 10-day course, vancomycin is given twice daily for a week, then once daily for a week, and then once every 2-3 days for [2 to] 8 weeks. I'm a bit concerned about vancomycin-resistant Enterococcus, but a pulsed dose after the first treatment is the new standard.

The alternative is to treat with fidaxomicin for 10 days.

Rifaximin after a standard dose of vancomycin may be considered [for patients with more than one recurrence].[2] Good luck getting that paid for.

Consider fecal transplant in patients with multiple recurrences.[2] I suggest considering fecal transplant after one episode of fulminant toxicity. Also, consider a 3- to 4-day course of vancomycin prior to fecal transplant to reduce the stool burden of the vegetative spores of C difficile.[2] Discontinue it the day before you do the fecal transplant. No strong evidence here, but I think it is a reasonable thing to consider.

What do we do for patients who get treated for CDI but continue to need their [systemic] antibiotics? The recommendation is to stop [CDI therapy] at the end of the 10-day course, but consider an empiric continuation in high-risk patients.[2] It may be that you go to vancomycin 125 mg daily or fidaxomicin 200 mg daily. The evidence is very much lacking, and there is no official recommendation for this population.

Probiotics

Probiotics are a really serious moving target.

Both the ACG guideline[1] and the current guideline[2] do not recommend the use of probiotics [for primary prevention]. Lactobacillus and Saccharomyces species have been purported as potentially beneficial [for preventing recurrence].[2]

These should not be used in intensive care unit patients. There are reports of bacteremia and fungemia occurring in patients with indwelling catheters when exposed to these types of probiotics.

Final Thoughts

High-level disinfection of bathrooms is not addressed in the current guideline, but it is a David Johnson recommendation. Spores can live in a vegetative state on countertops and surface areas. Spores can be shed from the toilet. Toilet microbiology in the bathroom is fairly well known, but there is strong evidence that it can be spread and people can auto-reinfect. Tell patients to disinfect their bathrooms with high-level mechanical-disruption scrubbing followed by a high-level disinfection with exposure to a Clorox-type–based treatment. I do this routinely in my practice, and I think it would be helpful for you to incorporate.

CDI is very prevalent and also a very expensive problem. It is the leading cause of nosocomial-related death in the United States. It is a daily issue of concern and topic of discussion, and we have a long way to go. Hopefully, these new guideline recommendations will provide you some guidance when managing the next patient you see with CDI.

I'm Dr David Johnson. Thank you again for listening.

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