Of 1,250 cases of Clostridium difficile infection that occurred during a 3.6-year period in one British community, fully 45% were genetically unrelated to all other cases and must have been acquired from sources other than symptomatic patients, according to a report published online Sept. 25 in the New England Journal of Medicine.
Only 35% of these C. difficile cases were genetically related to previous cases and involved patient contact with a hospital ward where other patients were being treated, and only 19% were genetically related and involved "some sort of hospital contact," said Dr. David W. Eyre of the National Institute for Health Research Oxford (U.K.) Biomedical Research Centre and his associates.
This indicates that hospitals and medical contacts are not the major source of transmission of this organism, and that other reservoirs – possibly asymptomatic carriers of C. difficile, colonized infants, farm animals or pets, food, and water – must be targeted to minimize exposure, they noted.
Until now, most episodes of C. difficile infection were believed to be acquired in health care settings, so prevention efforts have focused on symptomatic patients and their immediate environment. "The contribution of cases acquired from [other] sources to the overall burden of disease [has been] unclear," the researchers said.
Dr. Eyre and his colleagues quantified how much transmission is caused by symptomatic patients and how much by other environmental sources when they examined whole-genome sequences in isolates taken from all patients who had C. difficile infection in a defined geographic area. This region had a typical incidence of the infection and standard infection-control practices in place.
During the 3.6-year study period, 40,924 fecal samples were submitted for C. difficile–testing from symptomatic inpatients at four university hospitals, outpatients at these hospitals, outpatients at general medical practices, and outpatients at other hospitals in Oxfordshire.
A total of 2,377 of these samples tested positive for the organism on immunoassay, and 1,714 of these were culture positive. Of these, 957 were successfully sequenced.
The median age of these patients was 78 years (range, 66-86 years).
A total of 428 of the sequenced isolates (45%) were found to be genetically unrelated to all previous cases, indicating that the organisms were acquired from numerous diverse sources rather than by a few health-care-related transmissions, the investigators said (N. Engl. J. Med. 2013 Sept. 25;369:1195-205 [doi:10.1056/NEJMoa1216064]).
"It is striking that we observed diverse subtypes in patients with C. difficile infection, each representing a separate transmission event from a reservoir or asymptomatic carrier. Typically, one or very few cases arose from each exposure, reflecting both limited secondary transmission and the absence of widespread transmission from a few point sources," they noted.
A total of 333 sequenced isolates (35%) were found to be genetically related to at least one other isolate obtained from a previous case, closely enough to indicate transmission had occurred. Of these, 126 (38%) patients were treated on the same medical ward in which the related case was being treated, 5 (2%) were treated on the same medical ward after the discharge or recovery of the patient with the related case, 29 (9%) were in the same hospital but never on the same ward as the related case, and 21 (6%) had both ward contact and hospital-wide contact with the related case.
No hospital-based contact could be established for the remaining 152 of these 333 patients (46%). However, 15 of these patients attended the same general medical practice as a patient with a related case, and 17 lived in the same postal-code district.
"Overall, 120 patients (36%) had no record of any hospital or community contact with a previous genetically related case," which "may represent exposure to at least one intermediate host or source rather than direct contact," Dr. Eyre and his associates noted.
Some genetically related cases were clustered in time, but many others were separated by periods as long as 1 year. "Distinct subtypes were identified consistently throughout the study, suggesting that the cases arose from a considerable reservoir," the investigators said.
They added that further, detailed study of these patients will shed light on the location and nature of such sources, which have yet to be identified.
This study was supported by the U.K. National Institute for Health Research, United Kingdom Clinical Research Collaboration, Medical Research Council, Biotechnology and Biological Sciences Research Council, Department of Health, and Wellcome Trust. Dr. Eyre reported no financial conflicts of interest; his associates reported ties to numerous industry sources.
