Stealth C. diff: Asymptomatic carriers add another threat to emerging pathogen

CDC: 'We are not at the point of saying go after asymptomatic carriers.'

Investigators have found that asymptomatic carriers of Clostridium difficile "have the potential to contribute significantly to disease transmission," including causing infections with the highly toxigenic strain that has plagued hospitals with severe outbreaks.1 Stealth C. diff transmission is the last thing infection control professionals want to think about, especially when it is hard enough to contain the emerging pathogen by focusing on active cases with typical symptoms such as diarrhea.

Despite the findings, a leading C. diff researcher at the Centers for Disease Control and Prevention told Hospital Infection Control that ICPs still should focus their primary prevention efforts on long-term care residents and hospital patients with active, symptomatic infection. "At least in outbreaks, controlling C. diff transmission at the point of containing the patient with active disease appears to be able to control [spread]," says L. Clifford McDonald, MD, acting chief of the prevention and response branch at the CDC division of healthcare quality promotion. "We are not at the point of saying, 'Go after asymptomatic carriers.'"

Though the study focused on long-term care, the same problem may be fueling transmission in hospitals as residents are admitted as patients, says Curtis Donskey, MD, co-author of the study and director of infection control at the Cleveland VA Medical Center. "The [findings] are applicable to hospitals because 33% of the patients who were asymptomatic carriers were sent to our acute care hospital during the six months after the study was completed," he says. "These patients are often coming from the nursing home and they are carrying C. difficile on their skin."

Clinical factors, such as previous C. diff-associated disease and recent antibiotic use, may be predictive of asymptomatic carriage, the study found. Conceding that some attempt at active surveillance cultures is not practical for C. diff patients, Donskey suggested using a predictive model to trigger precautionary isolation during an outbreak. "If you just looked at patients that had a previous history of C. diff or had been on antibiotics in the past three months, that would predict about two-thirds of patients who had asymptomatic carriage," he says. "So hospitals that don't have the ability to do an anaerobic culture easily can identify a lot of the patients who are asymptomatic carriers."

However, there remain a portion of such asymptomatic patients who slip through the predictive model. "Patients will acquire the organism and become an asymptomatic carrier, but never get any kind of disease," Donskey says. "The patients develop an immune response and carry it asymptomatically."

In that regard, the research raises questions about how many asymptomatic carriers of C. diff with no history of long-term care residency may be reservoirs for transmission in hospitals. "There is no question that our data pertain mostly to long-term care, but we are currently doing some more studies to try and extend this to our acute care facilities to see how common it is," Donskey says. "It is probably less common overall in the acute care hospital, but we suspect it is still going to be significant."

Virulent strain detected

The findings also are troubling because the researchers discovered asymptomatic carriers had skin contamination with C. diff strains that included the toxigenic strain (ribotype 027) that has caused severe hospital outbreaks with heightened mortality. "About 37% of the asymptomatic carriers had the epidemic strain," reports Michelle Riggs, BS, lead author of the study and lab manager at the medical center. "It produces a higher amount of toxins in the body. Some of the literature says that the epidemic strain actually produces more spores. It is possible that because it produces more spores and it is resistant to more drugs, that it could be a lot hardier."

Adds Donskey, "We were a little bit surprised. The question we had going in to the study was since this strain is more virulent and toxic, are we going to see it being carried asymptomatically like other strains? We expected to see some, but people may be a little surprised that a strain we think of as so virulent can be carried by people without any symptoms."

However, some level of asymptomatic carriage of the epidemic strain is not surprising, McDonald says. The strain has been detected in retail meats and in community-acquired cases of C. diff.

"After someone has had C. diff many will continue to carry it," McDonald says. "Other asymptomatic people that have not had actual C. diff disease get it by nosocomial transmission in health care and long-term care settings. Did they get it from an asymptomatic person or an active person? We think it is primarily the symptomatic [patients], but there probably is some transmission from the [asymptomatic patients]."

Despite conceding that some low level of transmission may be occurring via asymptomatic C. diff carriers, McDonald emphasized that the focus should remain on C. diff patients with common symptoms such as diarrhea because they are the most likely source of transmission. "Someone with diarrhea is much more of a contagion risk," he says. "The question right now is do we have enough data to say that the contagion risk from asymptomatics is great enough that we should be isolating all these people using some kind of active surveillance mechanism? First of all, we are going to need some tests that would make it easier to do that, and I suspect that they will be available soon. But then we are going to have to see some evidence that it really contributes to containment [of infection transmission]."

Even if asymptomatic C. diff carriers could be easily identified, it still would raise several other thorny issues, including placing ever more patients in isolation and the lack of an effective decolonization protocol, he adds. "It won't work with metronidazole," he says. "And with vancomycin, all you will do is get the bug back when they stop the vanc and then they will carry it even longer. We have [insufficient] data right now to say that we should be trying to detect these asymptomatics and put them in isolation."

Skin carriage common

Overall, the Cleveland VA study found that 35 (51%) of 68 asymptomatic patients were carriers of C. diff, and 13 (37%) of the patients carried epidemic strains. Compared with noncarriers, asymptomatic carriers had higher percentages of skin (61% vs. 19%) and environmental contamination (59% vs. 24%). Eighty-seven percent of isolates found in skin samples and 58% of isolates found in environmental samples were identical to concurrent isolates found in stool samples. "Some observations from our study were unexpected," the authors noted. "First, approximately one-fifth of patients with negative stool culture results had skin and environmental culture results positive for C. difficile. We hypothesize that the presence of C. difficile on skin may have been attributable to prior stool carriage or to levels of stool colonization that were below the limit of detection." Although numerous studies have evaluated environmental C. difficile contamination, a new finding was the frequency of skin contamination among patients with active disease and asymptomatic carriers. Most concerning, "Spores on the skin of asymptomatic patients were easily transferred to investigators' hands," the authors concluded.

Though the findings strongly suggest that asymptomatic carriers may contribute to transmission of C. difficile infection, the authors concede that molecular typing of strains acquired by patients will be necessary to confirm that the exact strains from asymptomatic carriers are being transmitted. They did find that three subtypes carried by asymptomatic carriers were identical to isolates in infected patients. Although some epidemiological studies have suggested that asymptomatic carriers play a relatively minor role in disease transmission, the researchers also cited another paper that reported nosocomial acquisition of C. diff-associated disease (CDAD) in a hospital ward was epidemiologically linked to transmission from new, asymptomatic patients admitted to the ward.2

"It's been known over the years that there are a fair number of patients who carry C. difficile asymptomatically," Donskey says. "The presumption has been if you don't have diarrhea you are probably less likely to be a source for transmission. But [there is some research] that suggests that these patients could be important. People have kind of downplayed this data in the past, but it is a question that has come up with these current outbreaks that are going on. Maybe we should revisit this whole question of how important they are in transmission."

Control measures typically used for patients with suspected or documented CDAD include contact precautions until diarrhea has resolved, with patient rooms cleaned with a 10% bleach solution upon discharge. The problem is that asymptomatic carriers might not even be put in isolation. "We found we could get C. diff on our hands after touching these asymptomatic patients," he says. "Not with the frequency of those patients who have active diarrhea, but for patients who are asymptomatic carriers most health care workers are not wearing gloves and are using an alcohol hand hygiene product that may not remove the spores if you get them on your hands."

Gloves, bleach cleaning emphasized

The medical center took several additional infection control measures to minimize the impact of asymptomatic carriers and halt the outbreak. Those included terminal cleaning of all patient rooms with a bleach solution, extending duration of contact precautions and a heavy emphasis on glove use. Glove use was emphasized more than switching completely to plain soap washes, which are considered more effective against C. diff than the alcohol hand rubs that are now ubiquitous in hospitals.

"We are trying to encourage using gloves more frequently in the hospital," Donskey says. "We are trying to keep patients who had a history of C. diff in isolation longer and encouraging glove use for those patients."

Indeed, another thing to consider in an outbreak situation is keeping patients with C. diff in isolation even after symptoms resolve due to the possibility they have become asymptomatic carriers, he adds.

"I think 25% of the patients who were asymptomatic carriers had a previous history of C. diff," Donskey says. "They were treated, their symptoms resolved, but they were still shedding and they still had it on their skin. So, it makes sense that we might [extend precautions]. There is actually a lot of debate among infection control people about how long we should keep patients in isolation now. Our tendency is to lean toward being more conservative and keep these patients in isolation longer."

Adoption of a bleach cleaning regimen for all patient rooms appears to be the most effective intervention, he adds. "We used to use a regular hospital disinfectant, but those do not kill the C. diff spores. We made a switch so that all of our cleaning is done with bleach now. In the nursing home and even in the general hospital, we have gone toward using bleach for terminal cleaning of rooms. We have seen a significant decrease in our rates over the past year since we began using bleach throughout the institution."

Bleach cleaning is in line with CDC recommendations, but the focus should be terminal cleaning of rooms occupied by patients with active CDAD, particularly the bathroom, McDonald says.

"Frankly, if bleach cleaning had no downside to it you could say the more the better and just do the whole hospital," he adds. "But it does have downsides. It's caustic, corrosive, and there are ventilation issues. So until we have a sporicidal-like bleach that doesn't have those problems it makes sense to first focus on where the money is and that is in the known CDAD patient rooms. That is where our guidance leads people."

Still, ICPs facing an ongoing outbreak of C. diff in long-term care or hospital settings may want to consider some of the measures used at the Cleveland VA in case asymptomatic carriers are contributing to transmission, Donskey advises. "These patients could potentially play an important role in transmission," he says. "In the setting of outbreaks, if you are not getting a good response with the other measures, it would be reasonable to consider expanding terminal cleaning with bleach to rooms of patients that are not having diarrhea and potentially increasing the use of gloves in the hospital as well because the spores may be getting on health care workers' hands and being transmitted to other patients. That is pretty much what we have done here in our hospital in response to this data."

Don't expect any national C. diff recommendations to change based on the study, including those being jointly created by the Society for Healthcare Epidemiology of America and the Infectious Disease Society of America, says McDonald, a consultant on those joint guidelines. "[They] are not going to say anything different than what we are saying right now in terms of going after asymptomatic patients," he says. "In terms of bleach cleaning, you certainly can go beyond the circle of known C. diff patient rooms, but what we are saying is to begin there and work your way out."

References

  1. Riggs MM, Sethi AK, Zabarsky TF. Asymptomatic Carriers Are a Potential Source for Transmission of Epidemic and Nonepidemic Clostridium difficile Strains among Long-Term Care Facility Residents. Clin Infect Dis 2007; 45: (Oct. 15, 2007 issue) published electronically at http://www.journals.uchicago.edu/CID/
  2. Clabots CR, Johnson S, Olson MM, et al. Acquisition of Clostridium difficile by hospitalized patients: Evidence for colonized new admissions as a source of infection. J Infect Dis 1992; 166:561-567.