While CRE and other “superbugs” have been much in the headlines of late, Clostridium difficile has quietly become one of the most deadly pathogens in the country. Some 500,000 people are infected annually in the United States, with 29,000 patients dying within 30 days of the initial diagnosis of a C. diff infection (CDI). That is three times the number of people that have died from Ebola since the epic outbreak began in December 2013.
The CDC winnows the toll to about 15,000 deaths “directly attributable” to CDIs in a new study, making C. diff the leading cause of healthcare-associated infections (HAIs) in the country.1 A confluence of events has led to the CDI epidemic, including the emergence of the highly virulent NAP1 strain, the misuse and overuse of antibiotics, and the difficulty of removing C. diff spores from healthcare worker hands and contaminated surfaces. These dormant spores subsequently germinate in the gut of susceptible patients, who start the cycle again by shedding spores in diarrhea. As a result, there is essentially no margin for error in fighting the pathogen.
“It really is multifactorial. It is antimicrobial use and stewardship, but also environmental services, and getting healthcare workers to what they should do in terms of gowns, gloves, and hand hygiene,” says Jennie Mayfield, BSN, MPH, CIC, a clinical epidemiologist at Barnes-Jewish Hospital in St. Louis and past president of the Association for Professionals in Infection Control and Epidemiology.
Mayfield concedes a begrudging respect for the resilient, relentless pathogen, which all but dares the infection preventionist to stop it from reaching vulnerable patient populations.
“It is very challenging — a worthy adversary,” she says. “I have been facing down this organism for almost 15 years now, and it is still a little bit ahead of me.”
Most of the burden of disease is striking the elderly, with about 65% of CDIs and 80% of deaths occurring in people age 65 or older. More than 100,000 CDIs develop among residents of U.S. nursing homes each year. Meanwhile, excess annual healthcare costs are in the billions, in part because 1 out of every 5 patients with a CDI will suffer a recurrence of the infection and require additional care, the CDC reports.
“One out of nine patients over 65 years old with healthcare-associated CDI dies within 30 days of diagnosis — that is a frightening statistic,” Michael Bell, MD, deputy director of CDC’s division of healthcare quality promotion, said at recent press conference. The study was conducted at 10 sites in the CDC’s Emerging Infections Program (EIP), meaning the 2011 data reflect a broad geographic distribution.
“Because [alcohol] hand sanitizers don’t kill spores, it’s essential that you thoroughly wash your hands with soap and water to remove them,” Bell said. “This is one reason why we recommend glove use when caring for patients with C. difficile — to make it easier to maintain good hand hygiene. There’s no room for error.”
GLOVES GAINING EMPHASIS
Hand washing and C. diff have taken a long, circuitous route to get to the bottom-line advice in current thinking: emphasize glove use. In truth, neither alcohol rubs nor soap and water are really very effective at removing spores from hands. In the 2014 update to the compendium of infection control guidelines by leading infectious disease groups, wearing gloves was given as much emphasis as hand hygiene for preventing CDIs.
“Although in vivo studies demonstrate that C. difficile spores are resistant to alcohol, they also show poor log reductions (less than 2) for hand washing with soap and water,” the compendium guidelines state.2 “A 2013 study showed that only atypical products (e.g., ink and stain remover) could remove more than 1 log.”3
An earlier CDC report on the epidemiology of CDIs came to a similar conclusion: “Glove use, with strict adherence to changing between patient contacts, is the best proven method for preventing hand contamination with C. diff from symptomatic patients.”4
While the sequelae of any HAI can have some horrific presentations, it’s hard to imagine anything much worse than the hypervirulent NAP1 strain’s ability to spur life-threatening diarrhea and toxic damage to the colon.
“In the past, patients infected with C. difficile have had diarrhea that was often perceived as a nuisance but not a major problem,” Bell said. “Unfortunately, the type of C. diff circulating in the United States today produces such a powerful toxin that it can cause a truly deadly diarrhea — [an] intense illness that can include damage to the bowels so painful and severe that part of the colon needs to be surgically removed, a condition called toxic megacolon.”
Patients on broad-spectrum antibiotics are at risk for developing infections, as the drugs can wipe out commensal bacteria in the gut and leave the patient vulnerable to a CDI if spores are spread from an environmental surface or from another patient via hands of care workers. More than half of all hospitalized patients will get an antibiotic at some point during their hospital stay, but the CDC estimates that 30-50% of antibiotics prescribed in hospitals are unnecessary. Antibiotic misuse and imperfect infection control may increase the spread of CDI within a facility, and from there it can move across the healthcare continuum.
“Although people receiving care in hospitals made up two-thirds of all [CDIs], two-thirds of those actually occurred after the patient went home,” Bell said. “It’s essential that patients and their clinicians be aware that they need to take any diarrhea following antibiotic use very seriously. Shorter hospital stays are driving this trend, as incubating C. diff in the gut becomes symptomatic after discharge,” Mayfield said.
“The mean incubation period for the onset of disease following acquisition is [about] two days,” she said. “So you’re exposed, you get it in your gut, gut flora are altered, and you don’t become symptomatic until you’re home or in the nursing home.”
That said, the role of C. diff emergence and transmission in the community is poorly understood, she added.
“We know it is carried in farm animals,” Mayfield said. “It is out there in the environment. But because it is a spore, it is difficult to grow in the laboratory — that’s why its name is ‘difficile.’ In the [community] situation, it is even more difficult to obtain an isolate to do DNA typing”
Indeed, about 150,000 of the half million infections in the CDC study were community associated and had no documented inpatient healthcare exposure. However, an earlier CDC study found that 82% of patients with community-associated CDIs reported exposure to outpatient healthcare settings, such as a physician or dental office, in the 12 weeks before their diagnosis, suggesting again that the trigger for infection may be outpatient antibiotics.4 Another intriguing possibility is that, in addition to outpatient antibiotic use, the ambulatory settings themselves may be serving as environmental reservoirs for the transmission of C. diff spores — which can linger on antibiotic surfaces and fomites for prolonged periods.
“Studies have shown that CDI patients that have recovered from their diarrhea can continue to shed these spores in their stool for weeks to a couple months,” says Cliff McDonald, MD, senior advisor for science and integrity at the CDC division of healthcare quality promotion. “[Researchers have found that] examination tables and other ambulatory sites were contaminated with C. difficile spores. That is something that we’re very interested in understanding. Is it the exposure to the antibiotics — they receive the prescription in the doctor’s or dentist’s office — that led them to be vulnerable to C. difficile. Or was it also that they were exposed to the spores in that setting?”
A 2013 genome study revealed how poorly the routes of CDI transmission are understood, as researchers found that more than half of hospitalized cases did not acquire the organism from another patient in the hospital.5
“People have assumed that the vast majority of C. diff transmission comes from hospitals and goes out into the community,” Victoria Fraser, MD, co-director in infectious diseases at Washington University School of Medicine in St. Louis, said in describing the findings at a medical conference. “But what [these] identified really were dramatically [different] groups of acquisition, many of which could not be linked to another case — could not be linked to the hospital. We don’t completely understand the reservoir or the transmission for C. diff in and out of the hospital, the role of agriculture, or the role of food.”
Despite such unknowns, hospitals must reduce antibiotic use, practice meticulous infection control, and implement environmental cleaning to prevent CDIs. All those factors come with the caveat that they are dependent to some extent on the vagaries of human behavior, and it doesn’t take much of a breakdown in any of them for C. diff to find a victim.
There are system obstacles as well, as pressure to free and fill rooms may be a disincentive to rigorous environmental cleaning, Mayfield said. “Environmental cleaning and disinfection is a major factor in continued transmission,” Fraser said, noting that viable C. diff spores have been found in rooms where the previous patient did not even have a CDI.
“Some of the newer technologies such as UV light and hydrogen peroxide are great ideas, but we run into problems in that there is some down time,” she said. “You put the hydrogen peroxide in the room and it takes an hour. Meanwhile, the ER has four patients backed up that they needed to admit 10 minutes ago. There is this tremendous push to get patients into beds. When you are in that situation it’s really difficult to say, ‘No, we have to close off this room [for cleaning and disinfection].’”
Given the barriers to prevention, Bell’s recommendations to best the bug were daunting.
“C. difficile infections must be diagnosed quickly and correctly so that the infected patient can be cared for using the right infection control techniques, cleaning the environment near the patient with the right spore-killing disinfectants, ensuring perfect hand hygiene all the time, and also letting facilities know when a patient with C. difficile is about to be transferred to them so they can use the right infection control practices,” he said.
As noted, none of that is easy, and even the available tests have their own set of problems.
“There is no diagnostic test that makes the diagnosis for you,” McDonald said. “It’s a combination of the clinical symptoms of the patient, their situation, and a laboratory test. The old tests that were commonly being used all the time were the enzyme amino assays and they were generally not sensitive enough. PCR tests are now being more and more used ... they are much more sensitive. There is some controversy that sometimes they’re too sensitive.”
A case in point is the oncology population Mayfield works with. The chemotherapy these patients undergo can cause diarrhea similar to C. diff, but the PCR tests do not really differentiate whether someone has active CDI or is merely colonized, she said.
There are some forces at play that hold the potential to change this picture dramatically. For one, facilities working in concert can be effective, as CDIs dropped 20% among 71 hospitals in three states participating in targeted prevention collaboratives, the CDC reported.4
The Centers for Medicare & Medicaid Services (CMS) requires CDI reporting to the CDC surveillance system. Measuring typically precedes prevention in infection control, and C. diff should be no different. In 2017, the CMS will include CDI prevention in its value-based purchasing or “pay for performance” programs. As previously reported in Hospital Infection Control & Prevention, CMS is moving quickly to issue regulatory requirements for antibiotic stewardship programs, and may have a proposed rule on the table as early as this year.
“If we can improve antibiotic prescribing we expect to see rates of C. difficile infections improve dramatically,” Bell said. “In England, over a three-year period, they were able to push C. difficile infection rates down by over 60% just by doing a better job of managing how antibiotics are used.”
REFERENCES
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Lessa FC, et al. Burden of Clostridium difficile Infection in the United States. N Engl J Med 2015; 372:
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Ellingson, K, et al. Strategies to prevent healthcare-associated infections through hand hygiene. Infect Control Hosp Epi 2014;35: 937-960.
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Edmonds SL, et al. Effectiveness of hand hygiene for removal of Clostridium difficile spores from hands. Infect Control Hosp Epi 2013;34:
302-305.
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Centers for Disease Control and Prevention. Vital signs: Preventing Clostridium difficile infections. MMWR 2012;61:157-162.
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Eyre DW, et al. Diverse sources of C. difficile infection identified on whole-genome sequencing. N Engl J Med 2013;369:1195-1205.
