#54614: Clostridioides difficile Infection

Most anaerobic infections arise from sources indigenous to the patient. However, there are circumstances in which infection develops after acquisition of dormant bacteria from an exogenous source. The ability of organisms like C. difficile to produce spores makes them easily acquired from the environment. C. difficile is the main pathogen implicated in antibiotic-associated colitis and is the causative pathogen for 15% to 25% of nosocomial antibiotic-associated diarrhea [10].

As discussed, current strains of C. difficile may be less susceptible to available treatments, making its growing prevalence an even greater concern. One study noted the emergence and increasing prevalence of C. difficile strains with reduced susceptibility to both metronidazole and vancomycin [11].

C. difficile accounts for 20% to 30% of all antibiotic-associated diarrhea and is the most commonly identified reason for infectious diarrhea in hospital settings [10]. Because CDI is not a reportable disease in the United States, data are sparse. Only 20 states mandate hospital reporting either under state law or by incorporating the federal reporting requirements of the CMS. While state laws are more common, incorporation of federal reporting requirements is increasing. State surveillance activities have been heavily influenced by the CMS reporting requirements, which became mandatory in 2013. States that have not mandated reporting have taken other actions to reduce CDIs by implementing prevention collaboratives offered by the CDC [12].

The CDC Emerging Infections Program (EIP) was established in 2011 to monitor the incidence C. difficile infection and the burden of CDI in communities and hospitals within the United States. The EIP network consists of 35 counties in 10 states, with a surveillance population in excess of 12 million persons [13]. In 2021, 13,348 cases of CDI were reported to EIP. Of these, 49.3% were healthcare-associated and 51.0% were community-associated cases. The estimated incidence nationally was 55.9 per 100,000 population for community-associated CDI and 54.3 per 100,000 population for healthcare-associated CDI. Incidence rates were higher among female patients than male patients, among White patients than non-White patients, and among persons younger than 65 years of age than those older than 65 years of age [13]. Adjusting EIP data for enhanced sensitivity of diagnostic testing in the past decade, the estimated national burden of CDI decreased 24% from 2012 to 2017 [14]. This improvement was driven by a 36% decline in reported cases of healthcare-associated CDI. Although hospitalizations for CDI also declined by 24%, the number of first recurrences and in-hospital deaths did not change significantly. The estimated incidence of community-associated CDI was unchanged from 2011 to 2017 and accounted for almost 50% of the national burden of CDI in 2017. These data demonstrate the need for continued efforts to improve infection prevention and antibiotic stewardship in both inpatient and outpatient settings [14].

It is believed that long-term care facilities may be at the greatest risk for outbreaks. Because many of the patients in these settings are elderly and have been exposed to multiple antimicrobials, it has been suggested that the disease and colonization rates may be high [10]. An analysis of acute care hospital discharges in the United States found the discharge diagnoses of CDI doubled between 2000 and 2003. In 2003, close to 2% of patients discharged from acute care to long-term care carried the diagnosis of CDI [10].

CDI-associated medical costs also have reached historic highs. In 2015, the average cost for CDI case management and CDI-attributable costs per case were $42,316 and $21,448, respectively [15]. Hospital-onset CDI-attributable cost per case was $34,157, which was approximately 1.5 times the cost of community-onset CDI ($20,095). The average length of stay for inpatient treatment was 11.1 days. The total cost attributable to CDI in the United States is estimated to be $6.3 billion each year. Total annual CDI hospital management required nearly 2.4 million days of inpatient stay [15].

Historically, the mortality associated with CDI has been low. Death as a direct or indirect result of CDI occurred in between 2% and 9% of cases [10,13]. However, the mortality rate associated with CDI varies according to the patient variables and disease. While many patients with C. difficile-associated diarrhea recover without specific therapy, symptoms may be prolonged and debilitating. Progression to C. difficile colitis is a serious matter and carries a mortality rate as high as 25% in elderly patients who are frail [10]. Reports focusing on patients who are more seriously ill indicate mortality rates of between 10% and 30%. As incidence rates have risen over the past decade, so too have mortality rates, and both reflect, in part, an increase in the virulence of C. difficile strains. Several hypervirulent outbreaks have been caused by the North American Pulsed Field type 1 and polymerase chain reaction (PCR) ribotype 027 (BI/NAP1/027) strain [5,16]. This virulent strain has been associated with increased production of toxins A and B, fluoroquinolone resistance, and the production of binary toxin. The role of binary toxin is not clear, but it may synergistically increase the virulence of toxins A and B. The virulent strain BI/NAP1/027 has been reported in most states throughout the United States and in several countries in Europe [16]. Preventive strategies for BI/NAP1/027 are similar to those taken for other strains, including barrier methods, use of disposable equipment, handwashing (with soap and water), environmental disinfection techniques, and antimicrobial stewardship. Vaccines are under development to target the toxins, and a novel drug (SYN-004 [ribaxamase]) for preventing C. difficile is under investigation [17].

Advanced age is considered a risk factor for CDI, as evidence by the higher age adjusted incidence of CDI [23]. Age older than 65 years is considered a risk factor both for acquisition of C. difficile and for the development of C. difficile-associated diarrhea [23,24]. This difference in prevalence is not attributable to a greater exposure to antibiotics among older adults. The Society for Healthcare Epidemiology of America (SHEA) suggests that the greater morbidity and mortality of CDI in elderly populations may be due to age-related changes in fecal flora, immunosenescence, or the presence of other underlying diseases [23]. Frequent interactions with healthcare systems also may place the older adults at greater risk for CDI. Data from the EIP show that in 2010, exposure to health care preceded 94% of CDI. Of those, 75% were inpatient exposures, with the remaining 25% associated with long-term care facilities and outpatient care settings [25,26].

The most modifiable risk factor for the development of CDI is exposure to antibiotic agents. The antibiotics most frequently implicated in cases of CDI are clindamycin, cephalosporins, fluoroquinolones, and penicillins. However, virtually every antibiotic has been associated with CDI through the years. Even very limited exposure, such as single-dose surgical antibiotic prophylaxis, increases a patient's risk of both C. difficile colonization and symptomatic disease [10].

Healthcare workers are the most common hand carriers of C. difficile due to breaks in hand washing technique, actively caring for infected patients, and the existence of C. difficile spores on surfaces commonly touched by patients and workers alike. As such, longer hospital or facility stays increase the probability of contact. The risk of acquiring the disease during an admission increases with time and can be as high as 40% during longer hospitalizations [10].

A compromised immune system can allow C. difficile to proliferate, and immunocompromised patients are at an increased risk for CDI and poorer outcomes. For example, cancer chemotherapy often leads to immunosuppression, neutropenia, intercurrent infection, and prolonged hospital stays—all of which are associated with increased risk for CDI. Furthermore, evidence also suggests that C. difficile has become the most important pathogen causing bacterial diarrhea in patients with human immunodeficiency virus (HIV) in the United States [27]. Immunosuppression, either as a result of chemotherapy or disease process, can increase the probability of developing CDI; this risk may be compounded by concurrent use of antimicrobials or prolonged hospitalization [10].

Another risk factor for C. difficile is gastrointestinal surgery or manipulation of the gastrointestinal tract, including tube feedings [10]. It has also been hypothesized that the use of acid-suppressing medications, such as histamine-2 receptor antagonists and proton pump inhibitors (PPIs), may lead to CDI [28,29,30]. Although many studies suggest an association between using these medications and the acquisition of CDI, other well-controlled studies have suggested that the association is the result of prolonged hospital stays, prolonged use of PPI therapy, and underlying disease severity [10,30]. Additionally, a system review of observational studies suggests that patients who receive acid-suppressing medications may be at increased risk for recurrent CDI [31].

CDI is much less common in children than in adults. However, 2% to 70% of young children, depending on age and other factors, may be asymptomatically colonized with C. difficile, including toxigenic strains [21,32,33]. Colonization rates decrease as infants age, falling to about 6% by 2 years of age and down to 2% by 3 years of age [21]. Although infants may acquire colonization in the first week of life, no studies have shown a consistent association between mode of feeding (i.e., formula instead of breast milk) as viable factors. Colonization of infants younger than 1 year of age has failed to show an epidemiologic association with the development of disease. At the same time, nosocomial transmission in the neonatal intensive care unit (NICU) has been well documented, as has C. difficile contamination of the NICU environment [21]. In predominantly healthy infants without significant healthcare exposure, C. difficile colonization and acquisition reflect environmental exposure, with pet dogs identified as a novel risk factor [32].

One complication in the accurate diagnosis of CDI in young children is the lack of specific tests for this age group (such as the enzyme immunoassay [EIA]). However, it is important to remember that children who are colonized with C. difficile do represent a reservoir for disease transmission, even if they are asymptomatic. This returns to the issue of environmental cleaning, which has been recognized as a key factor in transmission prevention for many organisms [21,34].

The epidemiology of CDI in children may be changing with the emergence of BI/NAP1/027. Because this strain has been associated with severe disease in both adult and pediatric patients without recent exposure to healthcare facilities, testing for C. difficile should be considered in children 1 to 2 years of age with diarrhea and recent antibiotic exposure, especially when more common causes have been excluded. Children older than 2 years of age with diarrhea and a history of recent antimicrobial use may be tested with the same techniques used for older children or adults. Because the disease has been confirmed in asymptomatic children without recent antibiotic exposure, testing for C. difficile may be considered for these patients, but other diagnoses are more likely [21].

It is vital to remain vigilant regarding CDI even among populations previously believed to be at low risk for the disease, as virulence and infection patterns are changing [35]. Statistics indicate that CDI is occurring among healthy peripartum women, who have been previously at very low risk for the disease [33,36]. The frequency of the disease also seems to be increasing among persons living in the community, including, but not limited to, healthy persons with no recent healthcare contact. But, there are limited historical data against which to compare these statistics [10].

The primary mode of C. difficile transmission is person-to-person spread through the fecal-oral route, principally within healthcare facilities [10]. Asymptomatic patients (carriers) colonized with C. difficile may be shedding spores, a source of environmental contamination that facilitates transmission of infection to more vulnerable patients within the facility. Person-to-person contact permits C. difficile spores to pass readily from carriers and their bedding to the hands and clothing of healthcare workers. The hands of healthcare workers, transiently contaminated with C. difficile spores, are probably the main means by which the organism is spread during non-outbreak periods [10]. Studies have found a prevalence of asymptomatic colonization with C. difficile of 7% to 26% in acute care facilities and 5% to 7% in long-term care facilities, although other studies indicate the prevalence of asymptomatic colonization may be closer to 20% to 50% in facilities where CDI is endemic [37]. In a prospective, blinded cohort study in two university hospitals, the rate of hospital-acquired CDI among patients admitted to the same ward as an asymptomatic carrier was 4.6%, compared with 2.6% among patients residing in a ward having no asymptomatic carrier [38]. The risk of acquiring CDI correlated with the amount of exposure and length of stay.

As discussed, the longer a person remains hospitalized, the greater the exposure risk, which indicates a cumulative daily risk of exposure to C. difficile spores in the healthcare setting. In most cases, the period between exposure to C. difficile and the development of infection has been estimated to be a median of two to three days [10]. CDI resulting from exposure to C. difficile in a healthcare facility can also have onset after discharge [10].

Environmental contamination also has an important role in transmission of C. difficile in healthcare settings. Aside from transmission on healthcare professionals' hands and clothing, there have also been outbreaks traced back to electronic rectal thermometers, inadequately cleaned commodes, and bedpans shared between patients [10]. Environmental samples of C. difficile also have been obtained from homes, parks, chain stores, fast food restaurants, and other commercial sites [39,40,41,42].

The environment must be accepted as a critical source of contamination as it plays an important role in supporting the spread of infection. Because C. difficile is shed in feces, any surface, item, or medical device that becomes contaminated with feces is a potential source for the spores and can become involved in infection transmission. C. difficile spores can exist for five months on hard surfaces without adequate cleaning. In one study, spores were found in 49% of rooms occupied by patients with CDI and in 29% of the rooms with asymptomatic carriers [21].

The heaviest contamination is present on floors, in bathrooms, and on any surfaces commonly touched by hands, such as light switches, bed rails, and tabletops. Other potential contamination sites include thermometers, blood pressure cuffs, and call buttons [21].

One study noted that in samples of cooked and uncooked meat products, 42% contained toxigenic C. difficile strains. These findings indicate that food products may play a role in C. difficile transmission [41,43]. However, foodborne transmission is not considered a major part of the usual transmission cycle so far [44].

A case definition of CDI should include symptoms (usually diarrhea) and either a stool test result positive for C. difficile toxins, or detection of toxigenic C. difficile, or colonoscopic findings demonstrating pseudomembranous colitis. Clinical manifestations of infection with toxin-producing strains of C. difficile can be as varied as nonsymptomatic carriage, mild-to-moderate diarrhea, or a fulminant pseudomembranous colitis. A history of antimicrobial use within three months of the onset of diarrhea is characteristic. The most common symptoms of mild-to-moderate C. difficile disease are [10]:

Signs and symptoms of severe infection include:

As noted, fever, cramping, abdominal discomfort, and a peripheral leukocytosis are found in fewer than half of CDI patients [10].

According to the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA), patients with at least three unexplained and new-onset unformed stools in 24 hours are the preferred target population for testing for Clostridioides difficile infection (CDI).

(https://www.idsociety.org/practice-guideline/clostridium-difficile Last Accessed: September 11, 2023)

Strength of Recommendation/Level of Evidence: Weak recommendation, very low quality of evidence

Hospitalized patients and persons residing in long-term care facilities should be tested for CDI whenever they develop unexplained and new-onset diarrhea, defined as three or more unformed stools in 24 hours [10]. The diagnosis of CDI is made in one of two ways: a stool positive for C. difficile toxins or toxigenic strain of the organism, or endoscopic/histologic findings of pseudomembranous colitis. Testing of stool from asymptomatic patients is not clinically useful, even when used as a test of cure, and is not recommended except in epidemiologic studies [10]. Diagnostic stool evaluation should be considered in the patient with clinically significant diarrhea (i.e., three or more loose stools for at least two days), or performed immediately in the patient with severe diarrhea (10 to 15 stools in a 24-hour period), especially if combined with fever or recent antibiotic usage.

One important tool for understanding CDI epidemiology is molecular typing. In order to gain an accurate understanding of transmission and the settings for transmission, molecular characterization of isolates is necessary. Molecular typing can confirm a shift in epidemiology and allow tracking of certain strains. The BI/NAP1/027 epidemic strain of C. difficile was identified and distinguished from other strains using the PCR method of typing [10].

However, typing requires access to a stool sample, which may be difficult given the preference for nonculture diagnosis methods [10]. If a culture is obtained, molecular typing may be completed by examining polymorphisms after restriction endonuclease digestion of chromosomal DNA, PCR-based methods, or sequence-based methods. PCR testing is rapid and is the most commonly recommended method. The information gained from typing the C. difficile strain can assist in treatment decisions and determining prognosis. However, the SHEA/IDSA guidelines indicate that more data on utility are necessary before this methodology can be recommended for routine testing.

The important principles for effective management of CDI are as follows [10]:

When managing CDI there are important clinical and laboratory features to consider in assessing severity, choosing therapy, and judging prognosis. These include age older than 65 years, general debility, immunodeficiency status, renal function, and leukocytosis. A peripheral leukocytosis greater than 15,000 cells/mcL is indicative of severe colitis. Leukemoid reactions in the range of 30,000–50,000 cells/mcL are sometimes seen and may be a herald sign of toxic megacolon or impending bowel perforation [10].

Mild-to-Moderate Disease

For patients with an initial CDI episode, the IDSA and the SHEA suggest using fidaxomicin rather than a standard course of vancomycin. This recommendation places a high value in the beneficial effects and safety of fidaxomicin, but its implementation depends upon available resources. Vancomycin remains an acceptable alternative.

(https://www.idsociety.org/practice-guideline/clostridioides-difficile-2021-focused-update Last Accessed: September 11, 2023)

Strength of Recommendation/Level of Evidence: Conditional recommendation, moderate certainty of evidence

Mild-to-moderate illness is defined in the IDSA guidelines as CDI in the presence of a white blood cell count ≤15,000/mcL and serum creatinine <1.5 mg/dL [10]. In order to reduce selective pressure for vancomycin resistance in enterococci, previous recommendations were to initiate treatment with metronidazole for cases of mild-to-moderate illness. The 2021 focused guideline update recommends fidaxomicin over metronidazole for treatment of an initial or first recurrent episode of CDI [24]. The dosage is 200 mg twice daily for 10 days. Fidaxomicin is a first-in-class oral macrocyclic antibiotic with potent bactericidal activity against C. difficile [47,48]. Unlike vancomycin and metronidazole, fidaxomicin has a narrow spectrum of activity against normal gut flora. In settings in which access to fidaxomicin is limited, it is suggested to use vancomycin or metronidazole if the episode of CDI is not severe [24]. The suggested regimen is metronidazole 500 mg orally three times daily for 10 days, while the vancomycin dose is 125 mg orally four times per day for 10 days. The response to treatment is usually prompt, with a significant reduction in the rate of stooling within 24 to 48 hours. There are reports indicating that some patients infected with the BI/NAP1/027 strain respond more slowly, even unsatisfactorily, to metronidazole [16,49].

The 2021 focused guideline update also recommends coadministration of bezlotoxumab along with antibiotic therapy for patients with a recurrent CDI episode within the last six months [24]. Bezlotoxumab is a monoclonal antibody targeting toxin B produced by C. difficile and may be helpful in preventing recurrence in at-risk individuals.

The recurrence of symptoms following a successful course of therapy, and necessitating further treatment, remains a challenging problem. Up to 25% of patients treated for CDI have already experienced at least one previous episode [10]. In most cases, the recurrence of diarrhea represents relapse of the initial infection and is thought to be caused by residual vegetative spores that once again proliferate after therapy is lifted. The SHEA/IDSA guidelines list three options for re-treatment of a first recurrence of CDI [24]:

Options for treatment of a second or subsequent CDI recurrence include [24]:

In a randomized trial, oral fidaxomicin was found to be superior to vancomycin in preventing a second relapse in patients with a single recurrence of prior CDI. At 28-day follow-up, the relapse rate in the group treated with fidaxomicin was 20%, compared to 36% in the group receiving oral vancomycin [47]. Fidaxomicin appears to be an important therapeutic option for treating relapses and limiting recurrent disease.

Because disruption of the indigenous bowel flora is a major component of symptomatic infection and relapse, selected patients with multiple relapses have been treated by the instillation of stool (fecal microbiota transplantation) from a healthy donor. The rationale is to restore normal flora, and success has been reported in several uncontrolled case series. As stated, fecal microbiota transplantation is recommended for patients with multiple recurrences of CDI who have failed appropriate antibiotic treatments [10]. However, the use of this technique is limited by availability and logistics, expense, lack of health insurance coverage, and the need to screen the donor for potentially transmissible infections.

Fulminant CDI should be treated with vancomycin 500 mg four times daily orally or by nasogastric tube. Consider adding rectal instillation of vancomycin for ileus. IV metronidazole (500 mg every eight hours) should be administered together with oral or rectal vancomycin, particularly if ileus is present [24].

Although hand washing has been acknowledged as a clear necessity in the healthcare fields, consistent compliance with hand hygiene standards continues to be suboptimal. Despite the simplicity of the intervention, its substantial impact, and wide dissemination of the CDC guideline for hand hygiene, compliance with recommended hand hygiene has ranged from 16% to 81%, with an average of 30% to 50% [58,61,63,64,65]. Among the reasons given for the lack of compliance are inconvenience, understaffing, and damage to skin [61,64]. Across facility systems and organizations, consistent hand hygiene performance is an ongoing issue requiring continual attention.

Hand hygiene is a simple and effective way to prevent healthcare-acquired infections, especially C. difficile. Several studies have documented the reduction of healthcare-associated infections by improving hand hygiene compliance among healthcare workers between episodes of patient contact, but barriers to effective hand washing persist. The development of effective alcohol-based handrub solutions addresses these concerns, and studies have demonstrated that these solutions have increased compliance [59,60,65]. Unfortunately, it was discovered that C. difficile, in its spore form, is highly resistant to killing by alcohol. Healthcare professionals who attempt to decontaminate their hands with alcohol-based products may simply displace spores over the skin surface, without much reduction in the risk of transmission to other patients under their care. Residual spores are readily transferred by a handshake after use of an alcohol-based handrub [66]. Studies have shown that although the implementation of alcohol-based products has decreased the rates of MRSA and vancomycin-resistant Enterococcus (VRE), the rates of CDI do not change [10,66]. What does work is mechanical hand washing with soap and water after each contact with an infected patient. This practice physically removes the spores and reduces the likelihood of transmission. Therefore, hand hygiene should be performed with soap (or antimicrobial soap) and water before and after every contact with CDI patients, and gloves should be used and disposed of properly.

Staff, patient, and visitor education can be key to hand hygiene compliance as well as compliance with all measures to prevent and control CDI. Staff education must include all staff, not simply medical, nursing, or healthcare staff. Housekeeping staff must know how to protect themselves and how to adequately disinfect surfaces, especially those most likely to be contaminated, such as floors, light switches, bedside rails, call buttons, and tables.

Frequent in-services on patient care units as well as during orientation can ensure that all staff members are reminded frequently about the necessary precautions to prevent CDI. Signs posted on alcohol handrub can remind staff that hand washing with soap and water is required in a room with a CDI patient. Another key to compliance with hand hygiene and any infection control measures is monitoring and feedback to staff regarding compliance.

Patients and visitors should also be instructed that hand washing is an essential practice, and instructions on proper hand hygiene should be provided. Although most individuals know to wash their hands before eating and after using the restroom, few do little more than remove obvious dirt. Good hand washing involves removing the skin oils where organisms can remain even when the hands look clean. A quick pass under the water faucet and fast dry with a towel removes visible dirt, but the oils and organisms remain.

To effectively remove the oils and organisms, the process should take at least 20 seconds—the amount of time it takes to sing the song "Happy Birthday." The hands should be soaped and rubbed vigorously for 15 seconds to create a good lather and to assure that all parts of each hand are soaped and rubbed well. Then the hands should be rinsed thoroughly and dried, preferably with a paper towel. The towel should be used to turn off the water and then properly thrown away. Such hand washing removes the oils that harbor the organisms. Some mistakenly think that hot water must be used to kill the organisms. Water hot enough to kill organisms would be too hot to touch. Warm water mainly adds to comfort and encourages better washing technique.

The use of additional isolation techniques, such as Contact Precautions in addition to Standard Precautions, with patients with active CDI has been employed during breakouts with varied success. This addresses the transmission of C. difficile via patients with active CDI, but healthcare professionals' hands and the environment are equally efficient modes of disease transmission. Therefore, adhering to hand hygiene standards and stringent surface decontamination are equally important. The following descriptions of Contact Precautions are summarized from the 2007 Standard Precautions guideline and the 2017 SHEA/IDSA C. difficile guidelines [10,56]. The CDC website also provides updated guidance for clinicians and healthcare facilities on prevention of CDI, including isolation precautions, disinfection and sterilization, and hand hygiene [71].

Because C. difficile spore production can increase when exposed to nonchlorine-based cleaning agents and the spores are more resistant to commonly used surface disinfectants than vegetative cells, some investigators have recommended the use of dilute solutions of hypochlorite (1,600 ppm available chlorine) for routine environmental disinfection of rooms of patients with C. difficile-associated diarrhea or colitis, to reduce the incidence of C. difficile diarrhea, or in units with high C. difficile rates [57]. Acidified nitrite and preacetyl ions have also been found to effectively and safely destroy C. difficile spores [56].

The IDSA and the SHEA recommend accommodating patients with CDI in a private room with a dedicated toilet to decrease transmission to other patients. If there is a limited number of private single rooms, prioritize patients with stool incontinence for placement in private rooms.

(https://www.idsociety.org/practice-guideline/clostridium-difficile Last Accessed: September 11, 2023)

Strength of Recommendation/Level of Evidence: Strong recommendation, moderate quality of evidence

Improving hospital layout can have a markedly positive effect on the transmission of C. difficile from patient to patient [81]. In a cohort study of nosocomial acquisition of CDI, it was noted that double rooms had a higher rate of acquisition than single rooms, as did the exposure of a patient to a roommate with a positive C. difficile culture [10]. Another study example compared an older hospital with fewer single beds, higher bed occupancy, a low use of broad-spectrum antibiotics, and no antibiotic stewardship program to a newer facility with these programs. The more modern hospital with more private rooms had a lower rate of CDI; however, it was impossible to elucidate causation [10]. The difficulty comes in finding studies that provide enough quality, evidence-based information that bears out the theory of hospital layout affecting the CDI rate [10].

Research supports the fact that the great majority of patients with CDI have been recently administered antibiotics of some kind. However, antibiotic risk studies and prescribing intervention studies do not always consider exposure to C. difficile when assessing outcomes. In order to achieve a significant reduction in the incidence of CDI, it is necessary to limit the use of antibiotics known to increase risk for CDI. Antibiotics to be targeted should be based on the local epidemiology and the C. difficile strains present. Inpatient facilities should consider placing some restriction on use of fluoroquinolones, clindamycin, and cephalosporins (except for surgical antibiotic prophylaxis) [10]. The development of a healthcare facility program for appropriate antibiotic use is an important aspect of the control of C. difficile. Simply making lower risk agents available on the formulary is not sufficient; an antimicrobial stewardship program should be established [10].

Antimicrobial stewardship programs are interventions designed to ensure that hospitalized patients receive the right antibiotic, at the right dose, at the right time, and for the right duration [82]. These programs have been proven to improve patient outcomes, decrease length of hospital stays, and lower healthcare costs. Furthermore, research indicates that antimicrobial stewardship is one of two practices with good evidence of efficacy in preventing CDI [83]. As such, it is an essential aspect of preventing CDI in all healthcare settings. The core elements of a successful stewardship program are hospital leadership commitment, accountability, pharmacy expertise, implementation of interventions, tracking, reporting, and education [71,82].

Despite this proven efficacy, antimicrobial stewardship remains underutilized throughout the United States. The CDC has recommended the integration of stewardship programs at all facilities with the expectation that this one intervention would effectively prevent CDI and save lives [82]. A stewardship program assessment tool from the CDC is available online at https://www.cdc.gov/antibiotic-use/healthcare/pdfs/assessment-tool-P.pdf.

In the past, the administration of probiotics was thought to be an effective CDI preventive measure for patients receiving antibiotics. However, studies have not definitively shown them to be useful, although research has been difficult considering the diversity of probiotics used [84,85]. Additional problems include the lack of standardization, variations in bacterial counts in the products due to duration of storage, and potential for bacteremia or fungemia induction.

One randomized trial showed that drinking a probiotic drink with specific lactobacillus strains twice daily reduced the risk of CDI in patients older than 50 years of age taking antibiotics [86]. The study, however, was limited to a small number of patients in a selected population and excluded those receiving high-risk antibiotics. Larger, more diverse studies are needed before this practice can be recommended.

All surveillance programs, whether or not an outbreak is present, must have a standard definition of infection; use lab-based data, if possible; and track epidemiologically important variables, depending upon the organism(s) in question. The data must be analyzed and the analysis results communicated to all pertinent departments [56].

If an outbreak of C. difficile is identified, action must be taken to contain and alleviate the infection. If breaks in technique are tied to the outbreak or transmission, steps must be taken to correct the behavior, including the initiation of education interventions [56].

Basic infection control measures apply to all communicable diseases, including C. difficile. The most basic programs for prevention of the spread of infectious diseases include:

Although these measures are not C. difficile specific, they are important for the prevention of its transmission [56].

Performance measures are often developed according to the researched risk for C. difficile occurrence in a specific facility. No matter the level of assessed risk, standard performance measures are necessary. They include [10]:

One of the many issues affecting a facility's ability to attain quality measures and sustain them is the failure of healthcare providers to acknowledge the problem and commit to necessary changes. After performance improvement measures have been identified, they must be tailored to the practitioners and integrated into practice while building organization commitment. A practice that works in one system may require rearranging in order to work in another and be successfully sustained. It is essential to be inventive and adaptable to ensure that a change goes beyond current practice to sustained practice.