Most C difficile Infections May Not Be Spread in the Ward

Laird Harrison

February 13, 2012

February 13, 2012 — Less than a quarter of the Clostridium difficile cases in a hospital could be traced to patients in the same ward, challenging a common assumption about how the infection spreads, researchers report in an article published online February 7 in PLoS Medicine.

According to conventional thinking, C difficile is acquired by contact with symptomatic patients known to be infected with the bacterium. If correct, the new data imply that current infection control strategies will not be sufficient to contain the disease.

"A better understanding of other routes of transmission and reservoirs is needed to determine what other types of control interventions are required to reduce the spread of C. difficile," write A. Sarah Walker, PhD, from the National Institute for Health Research Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, and the Medical Research Council Clinical Trials Unit, London, United Kingdom, and colleagues.

To test the common theory about C difficile transmission, the researchers tested 29,299 stool samples from 14,858 patients with persistent diarrhea at Oxford Radcliffe Hospitals, using both enzyme immunoassay and culture. They found 1282 (4.4%) of the samples were positive for the bacterium by both tests.

The team then genotyped C difficile from each patient and used that information and data regarding when and where each patient was treated to establish potential transmission networks. Because links between some cases might be chance, rather than actual transmission, the researchers analyzed a control network of patients, using the same number of patients with enzyme immunoassay–negative diarrhea.

The investigators identified 69 types of C difficile and found that only 23% of patients shared the same type of bacterium as a patient already infected in the same ward.

When they allowed up to 8 weeks for possible transmission, , the authors found that 465 (66%) of the 705 test cases could not be linked to a donor.

They also found that the percentage of cases with a credible donor was highest in renal/transplant (37%), hematology/oncology (29%), and acute/elderly medicine (28%), with fewer linked cases in general surgery (20%), trauma/orthopaedics (16%), and other medical (13%) and surgical (6%) specialties.

When they used a maximum allowable infectious period of 12 weeks, this increased the proportion with credible ward-based donors to about 25%. When they decreased the maximum allowable incubation period to 4 weeks, this dropped the proportion with credible ward-based donors to about 17%.

In addition to challenging conventional thinking about how the bacterium spreads, the findings also call into question guidelines about the window for transmission. Instead of 48 hours after diarrhea resolution, these data suggest that the potential for transmission lasted up to 8 weeks, the researchers note.

The study raises more questions than it answers, the authors acknowledge. If the patients are not getting the organism from each other, where does it come from?

One explanation is that 7% to 26% of adult inpatients may be asymptomatic carriers, a route of transmission that needs further investigation, the researchers said.

In an accompanying perspective article, Stephan Harbarth, MD, from the Infection Control Program, University of Geneva Hospitals and Medical School in Switzerland, and Matthew H. Samore, MD, from the University of Utah, Salt Lake City, point out that 1 limitation of the study is the possibility of interward transmission.

It is possible that the patients spread the infection as they moved about within the hospital; for example, to get X-rays. Infections could also spread through equipment and healthcare workers caring for patients on multiple wards.

In addition, Dr. Harbarth and Dr. Samore point out, enzyme immunoassay testing is not very sensitive, so the researchers may have overlooked a pool of undiagnosed patients with C difficile. These patients might have been selected as control patients, introducing misclassification bias into the research.

Finally, the perspective authors note, the research does not record antibiotic exposure, which can affect the onset of symptoms, and in addition, the researchers did not evaluate possible transmission events linked to asymptomatic carriers.

These problems limit the practical implications of the research, Dr. Harbarth and Dr. Samore write. "The study by Sarah Walker and colleagues cannot provide definitive answers to these questions because it has significant limitations with respect to both issues."

Two of the study authors received honoraria from Optimer Pharmaceuticals and their institutions received support from the company for trial expenses on a per patient basis. Another study author reported receiving honoraria for consulting work or research funding from bioMerieux, Optimer, Novacta, Pfizer, Summit, The Medicines Company, and Viropharma. The perspective authors have disclosed no relevant financial relationships.

PLoS Med. Published online February 7, 2012. Article full text, Perspective

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