Antibiotics might not be the best answer for C. diff

Diarrhea seems sometimes like a forbidden topic, something to be whispered about or referred to with euphemisms. For most people, it's a passing inconvenience, but it can be a life-threatening situation for others. Diarrheal disease -- which stems from poor sanitation, unclean drinking water, and other infections -- is a leading cause of death globally in children under 5.

It can also be caused by the use of antibiotics to treat unrelated infections. In the United States, antibiotic-associated diarrhea is a serious problem, particularly for older or immunocompromised people. Ironically, when it's caused by a type of bacteria called C. difficile, or C. diff, the treatment is ... more antibiotics.

Balancing the treatment of potentially deadly infections with the need to reduce unnecessary antibiotic use -- which fosters the development of all kinds of drug-resistant bacteria -- is a tightrope clinicians walk regularly.

Because C. diff exists in an uneasy alliance with other gut bacteria, people can be carriers of the bacteria without experiencing symptoms. So determining which patients with diarrhea and C. diff to treat can be a tricky business. In general, C. diff infections are overdiagnosed and overtreated in this country.

Recently, Stanford Medicine infectious disease diagnostic specialist Niaz Banaei, MD, and his colleagues published a study in the Journal of Clinical Microbiology showing it's possible to safely avoid antibiotic treatment in a subset of people with a suspected C. diff infection. They do so by using a new testing method to identify the people most likely to benefit from antibiotics.

I caught up with him to learn more about the ways clinicians at Stanford Medicine are working to be good stewards of antibiotic treatments.

What is C. difficile, exactly? Why is it a concern?

Clostridioides difficile is a bacterium that can be found in the human gut and the environment. Most individuals carry C. difficile in their gut without experiencing any symptoms. These people are considered to be "colonized" by the bacteria.

However, when the community of microorganisms inhabiting the gut and contributing to our health is disturbed with antibiotics (usually prescribed for the treatment of unrelated medical issues), C. difficile can expand in numbers and produce toxins that can damage the lining of the large gut.

This can clinically manifest as diarrhea and gut inflammation, and death if not treated appropriately. More than 10,000 people die from C. difficile infection in the United States each year.

How is a C. difficile infection diagnosed?

C. difficile genetic material can be detected in a person's stool using a polymerase chain reaction, or PCR, test. We can also use a test called an immunoassay to assess the presence of the bacterial toxin in stool. Once an infection is confirmed, patients are treated with antibiotics that kill C. difficile.

But accurate diagnosis of C. difficile infection is complicated by the fact that people colonized by the bacterium can develop diarrhea that results from other causes. So even if the PCR test for C. difficile is positive, it's not certain whether the bacteria is the cause of a patient's diarrhea.

The toxin immunoassay detects only the presence of the toxins that can cause diarrhea. The downside of this test is that it misses some patients with C. difficile infection. In many hospitals, the decision to treat a symptomatic patient is left to the provider, based on their clinical suspicion for C. difficile infection and the results of both PCR and immunoassay testing. 

Why is it important to avoid overuse of antibiotics? Why is this complicated in patients with potential C. difficile infection?

Antibiotics save lives of patients with life-threatening bacterial infections. However, the inappropriate use of antibiotics can disrupt a healthy gut microbial community and promote the growth of drug-resistant bacteria. Antibiotics used to treat C. difficile infection can further disrupt the gut microbial community, which can allow C. difficile to recolonize after a subsequent exposure and, potentially, cause a future infection. 

Because laboratory diagnostics cannot definitively distinguish between C. difficile colonization in a healthy carrier and a true infection, the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America recommend that -- in order to avoid the unnecessary use of antibiotics in colonized patients -- C. difficile testing be done only in those patients with severe diarrhea in the absence of laxative therapy.

In 2015, my team led an effort to reduce the overdiagnosis of C. difficile through the real-time electronic tracking of diarrheal episodes and laxative administration. This enabled clinical laboratory personnel to verify that patients with orders for C. difficile testing met the current guidelines.

Stanford Medicine was the first health care system in the country to launch this intervention, which was shown to be highly effective in reducing hospital-onset C. difficile infection diagnoses without having any negative impact on patient care. Essentially it reduced the overdiagnoses of C. diff infection and helped doctors focus on other potential causes of their patients' diarrhea.

Tell us about the current study

Our prior study helped ensure that patients tested for C. difficile infection met the established guidelines, but there is still a need to reduce the overdiagnosis and overtreatment of C. difficile infection in patients who test positive for the presence of the bacteria.

We developed a new PCR testing method that allows laboratory personnel to infer the presence or absence of the C. difficile toxin from the PCR results alone. We collaborated with Stanford Medicine's division of infectious diseases, Infection Prevention and Control Program and Antimicrobial Safety & Sustainability Program to show that the dual reporting of C. difficile PCR and predicted toxin results helps doctors decide who should receive antibiotics and who doesn't likely need them, without worsening patient outcomes.

Given the findings, in November of 2017 Stanford Health Care started to only report the predicted toxin result.  

What did you find after this change?

Some observational studies argue that doctors should still treat patients with positive PCR tests even if they're negative for the presence of the C. difficile toxin. However, the clinical impact of providing or withholding antibiotic treatment in these patients had not been thoroughly investigated.

We found that, in a study of 600 hospitalized symptomatic PCR-positive, but predicted toxin-negative adult patients, reporting only the predicted toxin result resulted in a significant reduction in antibiotic therapy, and that there were no increases in adverse events for these patients. Altogether, our findings support the safety of limiting antibiotics for hospitalized patients with suspected C. difficile infection who show no signs of toxin in their gut.

Photo by Elena

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