C. difficile: the most common healthcare-associated infection

Clostridioides difficile haunts care facilities, causing additional misery for patients who are already ill. In its report on antibiotic resistance threats, the CDC classified C. difficile as an urgent threat—not because it is particularly resistant to antimicrobials, but because it most often strikes those who are taking or recently took antibiotics.

For healthcare facilities and their patients, C. difficile is a menace that causes a heavy burden of expense, illness, and even death.¹ Despite the urgency, various factors make it difficult to diagnose C. difficile and determine which cases are clinically significant.

Risk Factors and Symptoms of C. difficile

The bacteria C. difficile usually pounces on those who’ve recently taken antibiotics. In fact, people are up to 10 times more likely to get a C. difficile infection while taking an antibiotic and during the month after.² That may be due to the way antibiotics can disrupt the gut microbiome.

In addition to antibiotic use, other risk factors include being 65 or older, having a recent stay at a hospital or nursing home, having a weakened immune system, or previously being infected with C. difficile. Roughly 1 in 6 patients who are infected with C. difficile will become infected again within 2–8 weeks.²

For those infected, symptoms can develop within a few short days of beginning antibiotics or up to several weeks after taking them. The most prominent symptom is severe diarrhea. Other symptoms may include fever, stomach tenderness or pain, and nausea. A C. difficile infection can progress to more severe diseases such as colitis, toxic megacolon, perforations of the colon, and sepsis. In some cases, although rare, this escalation can lead to death.

**Impacts of C. difficile infections**

C. difficile can spread easily in healthcare settings, where people are often taking antibiotics and surfaces may become contaminated. According to the CDC, extended stays in hospitals and nursing homes can increase the risk of acquiring a C. difficile infection. In 2017, there were an estimated 223,900 cases of C. difficile among hospitalized patients.³

Furthermore, there were 12,800 estimated deaths from C. difficile in 2017.³ And more than 80% of deaths occur in people 65 and older.²

The overall estimated healthcare costs of C. difficile reached $1 billion in 2017.³

Implications for antimicrobial stewardship efforts

While C. difficile is not itself particularly resistant to antibiotics, antimicrobial stewardship efforts are crucial to reducing incidences of C. difficile infections. C. difficile usually strikes those who are taking or recently took antibiotics, efforts to reduce or improve antibiotic use are imperative. Between 30 – 50% of antibiotics prescribed in hospitals are unnecessary or incorrect,⁴ a disconnect that, if addressed, could reduce healthcare-acquired C. difficile infections.

Colonization vs. infection

Not everyone who acquires C. difficile will become sick. Healthy individuals who are exposed to C. difficile can become carriers with no outward signs or symptoms of infection. In fact, such colonization is more common than a symptomatic infection.

Unfortunately, those who are colonized with C. difficile can spread the bacteria to others, and the colonization can last for several months.

In some circumstances, people may carry C. difficile and have diarrhea and other symptoms—but their symptoms are not necessarily caused by it. For example, it’s possible for passive C. difficile carriers to become co-infected with another gastrointestinal pathogen. Additionally, a C. difficile carrier may have diarrhea for myriad other reasons such as inflammatory bowel disease, diet, laxative use, or side effects from other pharmaceuticals.

For these reasons, clinicians must consider a wide variety of factors when determining whether the presence of C. difficile is clinically significant.

Common laboratory testing methods

The strains of C. difficile most associated with symptomatic illness produce two exotoxins: toxin A and toxin B. That’s why many of the gastrointestinal testing options for C. difficile target one or both of those toxins.

Traditional stool culture for C. difficile is highly sensitive; however, this method comes with several drawbacks. First, it is extremely labor intensive and time consuming, with results taking 48 – 96 hours. Second, stool culture can lead to false positives when it detects non-toxigenic strains. To avoid this, isolates of toxin production can be tested. Finally, C. difficile toxin is very unstable and degrades at room temperature, meaning false negatives can occur if specimens are not stored properly and tested promptly.

Antigen testing is a rapid test that detects the presence of C. difficile antigen. However, antigen tests are nonspecific and are often used in combination with another test for the presence of toxins. For example, tissue culture cytotoxicity assays detect toxin B. This test is expensive, time consuming (24 – 48 hours), and requires technical expertise to perform.

A faster and easier toxin test is the enzyme immunoassay, which most often targets toxin B or a combination of toxin A and toxin B. In general, these assays are less sensitive than tissue culture cytotoxicity or toxigenic culture—and much less sensitive than molecular PCR testing.

The Syndromic Approach

The multiplex PCR BioFire^® FilmArray^® Gastrointestinal (GI) Panel identifies 22 pathogens commonly associated with gastrointestinal infections, including C. difficile, with results in about an hour. The BioFire GI Panel’s C. difficile assay targets both the toxin A and toxin B genes. Overall, the panel demonstrates 98.5% sensitivity and 99.2% specificity.⁵

These rapid results can help clinicians make quick decisions about isolation and other mitigation efforts in cases of healthcare-associated C. difficile infections. The syndromic testing approach, which identifies several targets in one GI pathogen panel, can also help clinicians know quickly if another pathogen is implicated in a case of suspected C. difficile. Rapid, comprehensive results can also help reduce additional or downstream testing.⁶

As with any gastrointestinal testing method, due to high asymptomatic carriage rates, the clinical relevance of the detection of toxigenic C. difficile from stool should be considered in the context of other clinical findings, patient age, and risk factors including hospitalization and antibiotic exposure.

Lab technician using the BioFire® FilmArray® Torch System.

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References:

Dongmu Z, et al. Clin Infect Dis. May 2018; 66(9):1326–1332.
C. difficile Fact Sheet. Accessed June 7 2021. Retrieved from: https://www.cdc.gov/cdiff/pdf/Cdiff-Factsheet-P.pdf
Antibiotic Resistance Threats in the United State 2019. Retrieved from: https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf
Information for clinicians about C. diff. Accessed on June 7 2021. Retrieved from: https://www.cdc.gov/cdiff/clinicians/index.html
The stated performance is the overall aggregate from the prospective clinical study data.
Axelrad JE, et al. J of Clin. Microbiology. 2019; 27;57(3). e01775-18.