European studies note high impact, spread of C difficile

Two new studies presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) are documenting the severe impact of Clostridum difficile infection (CDI) on hospital patients.

Meanwhile, other research presented at ECCMID suggests hospital transmission of C difficile, the most common source of healthcare-associated diarrhea, may not be the only route through which the bacterial pathogen is spread.

Higher risk of recurrence, death

In a study conducted in Scotland, researchers identified 3,304 patients hospitalized with CDI from August 2010 to July 2013 and matched them to a control group of 9,516 patients who did not have CDI. They were looking to determine the impact of CDI in hospital patients on mortality, length of stay, recurrence, and readmission.

The results showed that within 2 months of hospital admission, nearly a third of all CDI patients (29%) died, compared with 14% of the control group, and that the risk of dying of any cause was more than double in the CDI patients relative to the control group (hazard ratio [HR], 2.2). In addition, CDI patients stayed in the hospital on average 9.7 days longer than patients without CDI.

The researchers also found that of the 2,740 patients who survived the initial episode of CDI, 14% had a recurrence within 90 days; among the 371 who survived recurrence, 29% had a second recurrence. Overall, 60% the CDI patients were readmitted to the hospital within 6 months, though few readmissions were directly related to the infection.

The researchers, led by Alistair Leanord, PhD, of the University of Glasgow, calculated that the additional impact of CDI on the Scottish health service amounted to 11,300 bed-days per year, a finding they say is likely applicable to other countries.

"This is the equivalent to a 30-bed hospital ward being fully occupied all year," Leanord said in an ECCMID press release.

In the other study, a research team led by David Enoch, PhD, of Public Health England compared the impact of recurrent CDI infection among 6,874 patients treated at English hospitals for CDI from 2002 through 2013. Their study found that of the 1,141 (16.6%) patients who suffered a recurrent episode, 49% died within a year, compared with 38% of patients who had an initial CDI infection only.

After adjusting for patient demographics and clinical characteristics, recurrent CDI was associated with a significantly higher risk of death within 12 months (HR, 1.71). In addition, CDI-related complications—including dehydration and malnutrition—were more likely in recurrent CDI patients than in those with nonrecurrent CDI (21% vs 18%).

Both studies found that older patients (age 65 and above) bear the largest burden of CDI and recurrent CDI, a finding that Enoch said reflects the nature of the infection. "The main risk factor for developing C difficile infection is prior antibiotic use," Enoch said in the press release. "Older people are at greater risk of C difficile infection as they are often sicker, have other illness or conditions, and so need more antibiotics."

Antibiotic use is a critical factor in CDI because antibiotics can disrupt the balance of bacteria in the gut, eliminating the bad bacteria but also beneficial bacteria. Without good bacteria to keep it in check, C difficile can flourish in the intestinal tract, causing diarrhea and inflammation of the colon. And because CDI treatment requires more antibiotics, recurrence can be common.

Previous studies have shown that recurrence can occur in 20% to 30% of patients with an initial CDI and can climb as high 50% to 60% in patients with three or more episodes.

CDI emerged as a major public health threat around the turn of the 21st century, with increased incidence fueled by outbreaks of a virulent strain of C difficile in the United Kingdom, Canada, and the United States. Since peaking in 2007, CDI incidence has steadily declined in England, due in part to improved hospital hygiene. C difficile bacteria can be problematic for healthcare facilities because of its ability to survive on hospital surfaces.

Other routes of transmission

While hospitals are the most common offsetting for C difficile transmission and older patients are the most likely to be infected, virulent strains of community-associated CDI affecting younger patients with no healthcare exposure have also been on the rise and the epidemiology is less understood.

Some suspect C difficile is being carried around by patients who aren't showing any symptoms; others have suggested the bacteria are possibly being spread through the soil and water. And there are some who suspect that, since animals also carry C difficile bacteria, the infection might be spreading to humans through the food chain. No links between food animals and human CDI have been established, however.

To get a better sense of other potential sources of transmission of C difficile, David Eyre, PhD, a clinical lecturer at Oxford University, and a team of researchers performed whole genome sequencing on 625 C difficile isolates from stool samples submitted to hospital labs in 19 European countries. They focused on the 10 most common strains, or ribotypes.

What Eyre and colleagues found was that five of the ribotypes appeared to be concentrated in clusters within individual countries, an indication that those strains were likely being transmitted through hospitals. But the other five ribotypes appeared to be spread widely throughout Europe, with no evidence of in-country clustering, suggesting transmission by other sources—including food. One of the ribotypes they looked at—RT078—is the predominant strain of C difficile in animals and has previously been associated with pig farming.

"We don't know much about how C. difficile might be spread in the food chain, but this research suggests it may be very widespread," Eyre said in an ECCMID press release. He acknowledged, though, that the study doesn't provide any definitive answers and that more research is urgently needed to establish other transmission routes.

See also:

Apr 21 press release on Leanord and Enoch studies

Apr 22 abstract of Enoch study

Apr 22 press release on Eyre study

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