Hospital providers see increasing numbers of patients who present to the ED with pre-existing Clostridium difficile infections (CDI), prompting the need for increased infection control efforts to prevent transmission. Although isolation and effective sterilization procedures are important, experts note that the biggest weapon in the battle against CDI is an effective antimicrobial stewardship program.

  • Experts say that most cases of CDI stem from patients receiving antibiotics for another indication. For instance, some patients receive antibiotics in a doctor’s office or clinic setting, develop symptoms of CDI, and then present to the ED.
  • Data show that the incidence of CDI climbed steadily between 2001 and 2012, affecting roughly half a million patients and costing the healthcare system an estimated $5 billion annually.
  • While preliminary data from the CDC suggest the number of new CDI cases may be leveling off, cases of multiply resistant forms of the infection (mrCDI) have increased sharply, according to one new analysis. Investigators report the annual incidence of mrCDI increased by nearly 200% between 2001 and 2012.
  • Although most cases of CDI can be treated successfully with antibiotics, patients with treatment-resistant strains can suffer from severe disease, and even die from the infection.

Although healthcare providers are sharply attuned to the risks posed by Clostridium difficile infection (CDI), the incidence of this type of infection steadily climbed between 2001 and 2012. It’s the most common healthcare-associated infection in the United States. While preliminary data from the CDC suggest that the levels of CDI finally may be stabilizing, an increasing number of patients present to the ED with pre-existing CDI. This pushes this threat up the priority list for frontline providers.

“Our data show that more and more C. diff is coming from the community setting, so people are coming to the ED with symptoms already,” explains Vicki Allen, MSN, RN, CIC, FAPIC, the infection prevention director at CaroMont Regional Medical Center in Gastonia, NC, and chair of the communications committee for the Association for Professionals in Infection Control and Epidemiology. “We do track community onset of C. diff, and we see a lot of it coming from clinics. You would think that a lot of these patients would be coming from nursing homes, but we are not seeing that in our community.” Allen notes that the problem stems in part from patients who go to the doctor’s office with a viral infection and expect to walk out with a prescription for antibiotics, she says. “Then, they become symptomatic, and come to the ED,” she says.

Indeed, the development of CDI usually occurs because of receiving antibiotics for another indication, explains James Lewis, MD, MSCE, a professor of gastroenterology and a senior scholar in the Center for Clinical Epidemiology and Biostatistics at the Perelman School of Medicine at the University of Pennsylvania. “For example, people may have been hospitalized, and had surgery, and may have received antibiotics at the time ... or had pneumonia, and received antibiotics, and we think those antibiotics disrupt the normal community of bacteria that live in our intestines and allow C. diff to colonize and cause the infection,” he says. “Certainly, that can occur in patients who come to the ED from nursing homes, but it can also occur in ambulatory patients as well. Many ambulatory patients are treated with antibiotics, and some patients develop C. diff without apparent treatment with antibiotics.”

Lewis notes there are other reasons why the normal bacterial community might be disrupted. “A common example would be patients who have other underlying disorders of their intestines, such as ulcerative colitis,” he says. “But, more commonly, we see C. diff in patients who have been hospitalized and/or have been treated with antibiotics.” Of particular concern to frontline providers is the fact that C. difficile is resistant to normal sterilizing procedures and can spread easily in healthcare settings. Older patients are particularly vulnerable to CDI, which can cause diarrhea, severe gut inflammation, and blood infections or sepsis. While antibiotics are used to treat CDI, experts note that vigilance is needed, as the infection will recur in 30% of all cases.

Allen explains that it is important to immediately isolate patients who present with symptoms, such as diarrhea, and are suspected of carrying CDI. “Especially if a physician is ordering a specimen to rule out CDI, then we are assuming there is an infection until we know otherwise,” she explains.

Further, environmental services personnel are alerted to use bleach to clean that room because it will kill C. difficile bacteria. “If you are not isolating the patient and that room is not cleaned with bleach, then there is the potential that the pathogen will be still alive in the environment, heightening the opportunity for transmission,” Allen observes.

While all these steps are important, Allen notes that her hospital’s primary weapon in the battle against CDI is antimicrobial stewardship. “The literature says the primary risk factor for developing CDI is related to antibiotic usage,” she notes. “Consequently, the focus is on using the appropriate antibiotic for whatever pathogen [clinicians] are treating, and then using as short a course of antibiotics as possible.”

Allen adds that this is particularly important with respect to elderly patients who present with ailments such as community-onset pneumonia that require treatment. “It is just really important that [clinicians] focus on using the appropriate antibiotics for the duration that is necessary. These patients are already at risk because of their age and their illness, and so antibiotics pose an additional risk factor,” she observes.

Obtain Leadership Support

Allen’s hospital maintains an antimicrobial committee that collaborates with the clinical staff to disseminate guidance in this area and track antibiotic usage. “Physicians [serving on the committee] will round with the clinical staff, questioning antibiotic usage, and teaching nurses and other bedside caregivers about the importance of appropriate antibiotic use,” Allen explains.

For cases in which a physician has prescribed an antibiotic that is not the best choice according to guidelines, informed nurses can notify the physician to make a change, Allen observes. “Sometimes, people order an empiric therapy before they know the final results of a culture,” she adds.

Education, monitoring, and reporting all are important components in the prevention of CDI, Allen notes. “The other thing we are doing is trying to provide additional resources and education to the consumer, the patients and the clients in the clinics, on the importance of appropriate antibiotic use, not using unnecessary antibiotics, and then reporting symptoms if they do have them,” she says.

To bolster prevention further, Allen explains that hospital infection control staff members monitor infection trends in the community. “If we see certain trends at doctors’ offices or clinics, then we offer to provide education to them,” she says.

To carry out such efforts, it is important to have hospital leaders on board, says Allen. These leaders also can formulate incentives around appropriate antibiotic use to further motivate the clinical staff to make the issue a priority. “It is a matter of increasing awareness and keeping it up front and on the table,” she says. “We have very good support from our administration, and we also have good cooperation from our physicians. They are very receptive to the message.”

Consider Treatment-resistant Strains

While most patients with CDI recover completely with one or two courses of antibiotics, an analysis by Lewis et al suggests that cases of multiply recurring C. difficile infections (mrCDI), the most stubborn cases, are increasing rapidly. In a review of a large, nationwide health insurance database that includes more than 40 million patients, the authors found that the annual incidence of mrCDI increased by nearly 200% between 2001 and 2012. This compares to a 43% increase in the incidence of CDI over the same period.1

The analysis shows that the patients with mrCDI tended to be older and were more likely to be female than the patients with CDI. Also, the mrCDI patients were more likely to have been exposed to corticosteroids, proton pump inhibitors, and antibiotics before their diagnosis.

“There are several possible reasons [for these findings]. The most worrisome hypothesis is that the nature of C. diff is changing, meaning that the strains are changing and becoming more difficult to treat,” Lewis offers. He points to the recent emergence of the North American pulsed-field gel electrophoresis type 1 (NAP1) strain, which has been shown to be a risk factor for mrCDI, as one example. Other possible reasons for these findings include a change in treatment patterns or the possibility that some patients who present with what appears to be mrCDI may, in fact, suffer from something else, and they are misdiagnosed, Lewis says. “All of these hypotheses need to be explored further, and treatments are needed for patients who have these symptoms,” he adds.

One option that is used increasingly with patients who have experienced multiple reccurrences of the infection within a short period is fecal microbiota transplantation (FMT). Clinicians perform this procedure to provide an infusion of beneficial intestinal bacteria into patients to essentially compete with the C. difficile bacteria. The goal of the procedure is to help restore a normal population of gut bacteria, which will discourage the development of C. difficile. Although the approach is not FDA approved, Lewis notes that FMT is used fairly widely and available within the United States and around the world.

“There are multiple different ways that [this treatment] can be administered, ranging from colonoscopy, which is still probably the most common method, to enemas, upper endoscopy, to even administration of frozen fecal samples in capsules,” Lewis explains.

However, Lewis stresses that transplanting human feces into other humans is not likely to be the long-term solution to mrCDI. “The hope is that we can get smarter and figure out what bacteria or other microorganisms are essential for the effectiveness of this strategy so that those organisms can be grown in a lab and then put in a vehicle to be administered to patients,” he says.

Lewis notes that a small subset of patients with the most difficult mrCDI cases will go on to experience very severe disease. “Occasionally, people require having their colon removed as a treatment, and people have died as a complication of this,” he says. “Fortunately, that is a small minority, but it can be a fatal disease.”

There is some early evidence suggesting that aggressive antimicrobial stewardship programs and vigilant infection control practices finally may be making a dent in the incidence of CDI. The CDC’s Emerging Infections Program reports that a preliminary analysis of data from 2011-2014 shows a 9-15% decrease in cases of CDI nationally. Although these data are encouraging, public health officials stress that hospitals must maintain their focus on prevention. The CDC estimates that in 2011, CDI contributed to 29,000 deaths and 500,000 illnesses in the United States. That’s three times the number of deaths and illnesses from CDI that were tallied in 2000.


  1. Ma G, Brensinger C, Wu Q, Lewis J. Increasing incidence of multiply recurrent Clostridium difficile infection in the United States: A cohort study. Ann Intern Med 2017;167:152-158.


  • Vicki Allen, MSN, RN, CIC, FAPIC, Infection Prevention Director, CaroMont Regional Medical Center, Gastonia, NC; Chair, Communications Committee, Association for Professionals in Infection Control and Epidemiology. Email: Vicki.Allen@caromonthealth.org.
  • James Lewis, MD, MSCE, Professor of Gastroenterology, Senior Scholar, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia. Email: lewisjd@mail.med.upenn.edu.