The Clostridium difficile Epidemic: A Potential Disaster for Long-Term Care

The Scope of the Problem

Clostridium difficile (C. difficile), an anaerobic, spore-forming, gram-positive bacteria, has emerged in recent years as a serious health threat in the United States. Although the organism has been known to cause disease for at least 30 years,¹ recent mutations have resulted in healthcare–acquired epidemic outbreaks in the United States,^2-5 Canada,^6,7 Europe^8,9 and Japan.¹⁰ Genetic fingerprinting has identified a number of strains in clonal outbreaks, and several of these strains are cause for great concern. The rapidly spreading, hypervirulent, BI/NAP1 toxinotype III strain (also called PCR ribotype 027) has been responsible for many of the epidemic outbreaks. NAP1 toxinotype III strains produce 16 times more toxin than non-mutated strains of C. difficile. These strains are also resistant to some widely used antimicrobials and cause severe illness, including pseudomembranous colitis.^1,2,11,12 Relapse rates as high as 19% have been reported.⁹ Other recent strains with similar mutations have also caused widespread, healthcare–acquired clonal outbreaks.^13,14 Because genetic fingerprinting is rarely done, it is impossible to know the particular strains responsible for all of the outbreaks that are now occurring.

The number of cases of C. difficile–associated disease (CDAD) in the United States more than doubled between 1996 (82,000 cases) and 2003 (178,000 cases).³ A non–antimicrobial-resistant form of NAP1 toxinotype III was initially isolated in France in 1988, but cases were rare and sporadic.¹² Further mutations of the organism to the hypervirulent state resulted in epidemic outbreaks of CDAD in eight U.S. states² and Canada^6,7 between 2000 and 2003. Since 2003, similar outbreaks have been occurring throughout Europe, and the organism was identified and/or implicated in epidemic outbreaks in 16 European countries by 2007.^12,15,16

Attributable Mortality in the Older Patient

These epidemic strains are far more deadly than the organisms of 30 years ago. Redelings et al¹⁷ estimated that U.S. death rates for CDAD increased by 35% per year between 1999 and 2004. Mortality directly attributable to CDAD has been estimated to range between 6.0% to 6.9%.^18-20 C. difficile–attributable mortality for older persons is even higher. Pepin et al⁶ found that 14.3% of those between the ages of 65 and 74 years died within 30 days of diagnosis. For those over age 75 years, nearly 20% died as a direct result of the CDAD. Individuals who develop pseudomembranous colitis have a mortality rate up to 30% that is attributable to the infection.¹²

Risk Factors

Risk factors for CDAD include antimicrobial use, advanced age, comorbidities, and feeding tubes.

Antimicrobial Use 
The relationship between broad-spectrum antibiotic use and CDAD has been known for over 30 years¹ and is well documented. Fluoroquinolones (eg, ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin) and cephalosporins may place an individual at high risk.^5,20 However, antimicrobial drugs may no longer be a prerequisite to development of the disease. Recent studies suggest that 20%²⁰ to 30%²¹ of CDAD occurs in persons with no recent exposure to antibiotics within the previous one to two years. Dial et al²² found that 45% of patients taking a proton pump inhibitor–type medication had not received antimicrobials for at least 90 days.

Advanced Age
Older residents are at high risk for developing CDAD. Using the data from the National Hospital Discharge Survey, McDonald et al²³ found that the CDAD rate for persons over age 65 years was 228 per 100,000 population. For 45- to 64-year-old persons, the rate is only 40 per 100,000.³ Delmee et al²⁴ found that 20% of patients hospitalized with CDAD in Belgium had been transferred to the hospital from a LTC facility.²⁴ Because older adults are at significantly increased risk for this highly contagious infection, preventing CDAD epidemics in LTC settings presents a major challenge.

Comorbidities
Overall state of health plays an important role in how well a resident will be able to avoid infection. Several comorbidities have been found to increase the risk of CDAD including cancer,^22,25 chronic obstructive pulmonary disease,⁵ diabetes,²⁵ immunosuppression,^25,26 inflammatory bowel disease,22 methicillin-resistant staphylococcus aureus diagnosis in the recent past,²² pneumonia,¹⁷ renal failure,^17,22,25 and septicemia.¹⁷

Corticosteroids, which are often prescribed for asthma, chronic obstructive pulmonary disease, and autoimmune disorders, also increased the risk of contracting CDAD.²⁵ In addition, LTC nurses should be aware that residents taking proton pump inhibitors, such as omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole, for gastroesophageal reflux disease (or other reasons) are particularly at risk for contracting this infection.^22,25,27

Feeding Tubes
Residents with feeding tubes are more likely than those without to contract CDAD.^14,20,27 Contamination of equipment used for feedings may increase the bacterial load that the resident is exposed to. Although C. difficile spores are not affected by gastric acid, the actively reproducing, vegetative cells are.²⁷ Tubes that are inserted below the stomach, for example, jejunostomy tubes, totally bypass this protective mechanism and further increase the risk for infection.²⁸

Sources of Contamination

Sources of contamination include environmental surfaces, airborne transmission, asymptomatic carriers, hand hygiene, food sources, and spore formation.

Environmental Surfaces
When a CDAD outbreak occurs, it can happen very quickly, as the organism can be transferred from one patient to the next very easily due to environmental contamination. C. difficile has been cultured from a number of frequently handled environmental surfaces, such as bed frames, radiators, commodes, storage compartments, floors, door frames, door handles, call bells, water faucets, telephones, and other surfaces.^13,29,30 Fawley et al¹³ conducted a 51-month study at Leeds Teaching Hospital in the United Kingdom. A total of 192 cases of CDAD were identified in patients during this time period. The researchers obtained a total of 2550 environmental swabs from two wards, and 886 of these samples were positive for C. difficile. The organism was also cultured from the hands of healthcare providers. Because up to 93% of isolates were a single genotype (clonal), cross-contamination had occurred.¹³

This is an anaerobic organism (thrives in the absence of oxygen), and anaerobes usually die rather quickly in room air. When plated onto a dry glass slide, vegetative C. difficile cells that are actively reproducing die within 15 minutes. However, vegetative C. difficile cells have been shown to survive in room air on moist, nutrient-free agar for at least three hours, with some strains surviving up to 12 hours. Moist surfaces such as toilets, sinks, food trays, beds, linens, dressings, and even skin may be ideal settings for vegetative C. difficile.²⁷

Airborne Transmission
It is also apparent that C. difficile can be transmitted through the air. In one study, 554 environmental samples were taken from “high-reach” areas, such as over-bed lamps, bed bay partitions, the tops of doors and windows, curtain rails, and smoke detectors. Of these, 12% to 15% were positive for C. difficile.¹³ Roberts et al³⁰ showed that aerial dissemination of C. difficile occurred by collecting 23 isolates directly from the air during a two-day period. Twenty-two of these isolates were clonal, but the last known case of CDAD on that particular hospital ward was seven weeks prior to the sampling dates.³⁰

Asymptomatic Carriers
When Kyne et al³¹ prospectively tested 271 hospital patients, they found that 14% were asymptomatic carriers of C. difficile and that an additional 7% of patients became infected but remained asymptomatic while hospitalized.³¹ In a LTC setting, Riggs et al29 found that 51% of the residents were asymptomatic carriers of C. difficile. Whereas C. difficile was cultured from the skin of only 19% of the patients in isolation (the known infected), 61% of skin swabs obtained from asymptomatic individuals were positive for the organism. For environmental samples, 24% of the swabs from areas with patients with CDAD were positive, but 59% of the samples taken from rooms of asymptomatic carriers were positive for C. difficil. These were not non-toxic, non-infective organisms in 87% of cases; skin samples yielded the isolates identical to the concurrent disease-producing isolates found in stool samples, showing that all were clones of the same strain. The researchers demonstrated that spores could transfer easily from skin sources to the caregiver’s hands.²⁹

Hand Hygiene
It is well known and well documented that alcohol-based handrubs are not effective against C. difficile. Soap-and-water handwashing for at least 30 seconds is highly recommended.³²

Food Sources
The primary mechanism for transmission of the illness is fecal/oral contamination. Therefore, scrupulous handwashing and meticulous cleaning of cooking and serving utensils, bowls, etc, is imperative. Contaminated food may, however, contribute to the problem. Rodriguez-Palacios et al³³ isolated C. difficile from 11% of calves³³ and 20% of packaged ground beef purchased in retail stores in Ontario and Québec, Canada.³⁴

Spore Formation
Vegetative cells of C. difficile convert to spores in response to hostile environments. Spores have tough outer covers that protect the metabolically inactive microorganism from nutrient deprivation, dehydration, extreme heat, freezing, ultraviolet light, and chemicals that are toxic to the vegetative cell. C. difficile spores can survive on environmental surfaces for months,³⁰ and possibly even longer. Spores of C. difficile have been shown to survive gastric acid,²⁷ survive on uniforms washed for 10 minutes at 140 degrees F (60 degrees C),³⁵ and survive in contaminated ground beef cooked at 160 degrees F (71 degrees C).³³ Further complicating the situation, most commercially available cleaning solutions used in healthcare settings do not kill C. difficile spores. Hypochlorite-based disinfectants or household bleach should be used for cleaning.³²

The Impact on Long-Term Care Facilities

The Numbers
The number of patients with CDAD discharged from an acute care to a LTC facility increased from 20,000 in the year 2000 to 57,000 by 2003.³ Given the trends observed since 2000, this number is likely to steadily increase. Greater severity of illness and increased hospital lengths of stay associated with CDAD increases the probability that LTC placement will be required.

The Costs
McDonald et al³ determined that CDAD-attributable costs have increased healthcare expenses by $600 million per year. The authors state that this figure does not include the costs of medications and infection-control measures required in LTC facilities.³ Dubberke et al³⁶ estimated that expenses directly attributable to CDAD added an additional $2454 to the costs of an acute-care hospitalization. Total costs for a 180-day stay were calculated at $5042 per patient.³⁶ Because hospitalized patients requiring extended lengths of stay are frequently transferred to LTC facilities, most of the 180-day costs are borne by the facilities. Using secondary analysis, it is evident that having just six residents with CDAD would siphon $5000 per month from the nursing budget (a total of $30,252 for the 180 days). Given that C. difficile can easily infect the majority of residents in the entire facility within a short period of time, the result could be financially devastating, without even looking at the increased risk of liability.

Suggested Strategies

Educate the Entire Staff and the Residents
Be proactive! The more that staff and facility residents know about prevention of cross -contamination, the greater the probability that infections will be identified early and controlled. Educational programs need to be targeted for anyone and everyone who plays a role in the facility, including nurses, therapists, nursing assistants, activities staff, nutrition assistants, housekeepers, maintenance workers, and physicians who make rounds. It is not uncommon for inservices to be geared toward the professional staff, and though these efforts are clearly needed, the nursing assistants provide the majority of personal care related to toileting and personal hygiene.

Educating the housekeeping staff is absolutely critical given the degree of environmental contamination associated with C. difficile and the resilience of this organism. If, for example, the same water and/or mop are used to wash floors in the bathroom of a resident with CDAD and then used in the hallway, spores will likely be carried from the original site of contamination into the hallway, putting others at risk. With regard to controlling potentially infectious diseases, the housekeepers (often the lowest paid and most “invisible” of all healthcare workers) play one of the most important roles.

Residents have a vested interest in controlling infection in their facilities. Many residents have experience and skills from their pre-retirement lives that can help with the facilities’ overall infection-control program. Alert and oriented residents can assist with monitoring handwashing, reminding staff, residents, and visitors as needed. They can help to report areas of the environment that are soiled or in need of attention. Residents who are educated about C. difficile will be more likely to report abnormal bowel movements and more likely to ask family members who are reporting diarrhea to stay home.

Memory-support units provide a greater challenge, as residents sometimes wander into isolation rooms, put on other residents’ clothing, or take naps in someone else’s bed. Although many, many repeat instructions will be needed, reminding memory-support residents to wash their hands with soap and water after toileting, before eating, and frequently throughout the day will help to decrease fecal/oral contamination.

Identify Potential Problems and Isolate ASAP
When nurses and aides have a high index of suspicion, understand the importance of diarrhea, and can recognize the distinctive, foul odor of C. difficile, the battle is partially won. In one facility in which this author worked, it was the vigilance of the nurses, nursing assistants, and therapists that reduced the frequency of spread due to cross-contamination almost overnight. Aides reported diarrhea, nurses placed the resident into isolation (gowns and gloves), notified the interdisciplinary staff, and obtained orders for C. difficile toxin testing as soon as the problem was identified. Everyone reminded everyone else about the importance of soap-and-water hand hygiene. If a staff member or physician forgot to wash her or his hands, the person was reminded to do so by someone. As a direct result of these actions, in addition to changes in housekeeping chemicals and the use of probiotics, cases of LTC–acquired CDAD became rare within weeks.

Isolation is not an easy situation in LTC. If the bathroom is located inside the room, there is a high probability of recontamination of the hands on the door handles.

Instruct staff to wash their hands a second time after leaving a room. The resident’s room is her/his home, so it is not so easy to simply transfer rooms. It is very difficult to isolate one person in a two-bed room and to protect the other resident. It is, however, extremely important to do so, as the roommate is at increasing risk with each passing day. If the facility is designed to be home-like, boxes of yellow gowns and big red bags to hold the discarded gowns, though absolutely necessary, are definitely going to change the atmosphere. Be prepared for visitor questions. Consider keeping a room open for isolation so that residents who develop CDAD can be temporarily transferred.

The CDC recommends placing anyone with known or suspected CDAD on contact isolation immediately. Isolation should continue until the diarrhea has stopped completely. A private room is the ideal situation, but if this option is not available, then it is possible to cohort two residents, both of whom have CDAD, in the same room. Gloves should be worn at all times, and gowns are highly recommended when soiling of clothing is possible.³² Because transfer of C. difficile spores to care providers occurs frequently and easily through contact with a resident who has the infection and contaminated environmental surfaces, this author recommends that gowns be used routinely for all hands-on care. Keep in mind that asymptomatic carriers may also shed the organism.

Recognize the Limitations of Diagnostic Testing
The vast majority of labs in the United States use some form of C. difficile toxin immunoassay to determine whether a resident has CDAD. The toxin tests have their benefits, in that they are not labor-intensive, and they generally identify cases of CDAD quickly at relatively low cost. There are issues, however. Some of the tests require that the specimen be handled in certain ways so as to prevent toxin degradation and a subsequent false-negative test. For example, some tests require that the specimen be stored at 35.6 to 46.4 degrees F (2 to 8 degrees C) and be processed within 24 hours (or sometimes 72 hr).^24,37,38

This type of handling requirement may present problems for LTC facilities that have a lab that is closed over the weekend, or have to outsource to an external lab that may pick up from an outside box once or twice a day. Check with the lab that is used, ask for a package insert for the tests that are in use, and educate the staff appropriately.

Some studies have demonstrated that toxin testing is not as accurate as once thought. Delmee et al²⁴ found that the toxin assay detected only 56.7% of the 820 toxigenic isolates evaluated in their study.²⁴ Johal et al³⁹ found that 52% of hospitalized patients with pseudomembranous colitis secondary to C. difficile had negative toxin immunoassays.³⁹ Some labs have decided to use alternative methods of detection, such as cell culture cytotoxicity⁴⁰ or toxigenic cultures²⁴ instead of toxin immunoassays. The bottom line is that if the nurses’ observations of character and odor of the stool suggest C. difficile, assume that it is C. difficile until a toxinogenic culture, cell culture cytotoxicity, or colonoscopy proves otherwise.

Determine the Source

If signs and symptoms of CDAD occur after 48 hours, then it will be considered a LTC–acquired infection. If the resident arrives with active CDAD or develops diarrhea within 48 hours of arrival,^5,23 then the infection is not LTC–acquired. Notify the referral source.

Review the Admission Process

Long-term care facilities are dependent upon referrals from other healthcare and community sources. Caring for residents with CDAD is costly, isolation is necessary, and human resources within the facility are limited. So, accepting new residents with CDAD is a difficult decision. On the other hand, it is necessary to maintain strong relationships with referral sources and to keep beds filled.

Whatever policies the organization leaders decide upon, these decisions need to be based on consideration of all of the factors discussed above, as well as needs specific to the LTC facility. It is extremely important to identify potential residents with active CDAD before they arrive. Ensure that nurses and social workers screening referrals understand the complexities of CDAD, as they may need to educate referral sources. It may be necessary to revise the admission screening form to include questions about active diarrhea. Determine whether the facility will require C. difficile toxin screening or if toxigenic cultures will be needed in the event that a potential resident has unexplained, ongoing diarrhea and a negative toxin immunoassay. Decision makers must balance the need for information critical to the safety of existing LTC residents with the increased costs that will be required of the referral source. If the organization decides to admit residents with CDAD, then it will be important to initiate isolation immediately upon arrival in order to assure the safety of other residents and facility staff.

Get Help

Most LTC facilities do not have a dedicated infection-control professional (ICP) or the funds needed for such a position. Findings show that hospitals with a higher ICP-to-bed ratio had a lower prevalence of CDAD.⁴¹ The amount of information related to infection control, multi-resistant organisms, and infections such as C. difficile is too much for a non-ICP nurse or physician to keep up with. If the facility is experiencing unexplained outbreaks of CDAD, get help. If the LTC facility is connected to a hospital, contact the hospital ICP and ask for assistance with education and tracking. If the LTC is freestanding, consider hiring an ICP consultant, or contact the state Department of Health. Although some additional costs may result from being proactive, these costs will, in the long run, be far less than those associated with treating residents who develop CDAD at the LTC facility; damage to the facility reputation if an epidemic of LTC–acquired CDAD occurs; the liability associated with failure to protect existing residents from the risk of CDAD illness, and quite possibly death; or workman’s compensation claims related to healthcare provider CDAD.

Summary

C. difficile represents a serious threat to the health and well-being of LTC residents. Epidemic outbreaks, particularly those associated with newer hypervirulent mutated strains, are becoming a widespread problem. Older persons are particularly susceptible. Proactively addressing the risk factors can prevent excessive costs, needless suffering, and even death.

The author reports no relevant financial relationships.