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C Diff Molecular Screening Strategy Reduces Incidence, Saves Money in Canadian Study

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NEW YORK (GenomeWeb) – A hospital in Quebec has found that screening every patient for Clostridium difficile and isolating asymptomatic carriers of the gastrointestinal infection reduced illness and also saved money overall.

Published in JAMA Internal Medicine last week, the research could support implementation a similar strategy in other hospitals, but for future mutli-center research this could also require using a single test platform in all study hospitals. The research used an older assay from Becton Dickinson, but there are now many other options commercially available.

Of the 7,599 patients screened via rapid PCR of a rectal swab at the 345-bed Quebec Heart and Lung Institute, approximately 5 percent were found to be carriers of C. diff bacteria.

"We have known for a long time that [carriers] outnumber symptomatic patients," Yves Longtin, chair of the Infection Prevention and Control Unit at Jewish General Hospital at McGill University and lead author on the study, told GenomeWeb in an interview. 

"These patients are contagious and can contaminate the environment and healthcare workers' hands, but previously we thought that their role was relatively minor in the dissemination of C. diff in the hospital," Longtin said.

That is because carriers shed 1,000 times less C. diff and are not as contagious as symptomatic patients with active diarrhea. However, they are "much more numerous."

Quebec has had mandatory C. diff infection reporting for more than 10 years, so the authors were able to compare the consequences of isolating carriers to past results at the study hospital, as well as to 94 other hospitals in the province.

They ascertained that isolating carriers prevented 63 infections, or about 62 percent of the expected number of infections over the 15-month study period. The hospital previously had an average of six cases per 10,000 patient-days. By way of comparison, an epidemic in 2006 caused 28 cases per 10,000 patient-days, but currently the hospital has two cases per 10,000 patient-days.

Meanwhile, all other hospitals in the province had no statistical difference in infection rates over this same period.

Unlike typical infection control procedures for patients with active infections, the study used somewhat relaxed isolation procedures for C. diff colonized patients.

They were semi-isolated, with two patients per room. Hospital staff members were not required to wear gowns, but were encouraged to use gloves when treating these patients, and rooms were thoroughly disinfected after patients were discharged. Also, the contact precautions did not carry over if the patient moved around within the hospital, for x-rays or other procedures for example.

The screening evaluation is ongoing, but the rates are now the lowest among all teaching hospitals in the province, Longtin said.

C. diff is also the number one nosocomial infection in the US, he noted, with 400,000 cases each year leading to 30,000 deaths and costing more than $4 billion in excess medical costs.

Yet, the cost-benefit analysis in Longtin's study suggested universal PCR-based screening and isolation of asymptomatic carriers could actually save money.

The intervention cost a total of around $130,000 over about one and a half years. The researchers estimated each C. diff case costs $3,000 to $10,000, so the intervention avoided costs of between approximately $216,000 and $627,000.

The cost of intervention, which Longtin emphasized is a rough estimate, is driven mainly by the cost of the assay, but also includes the cost of isolation precautions and the extra disinfection of the room when a carrier patient leaves.

The cost savings was somewhat surprising, Longtin said. But, "It turns out C. difficile costs so much that if you have an intervention that can prevent half of the cases, it rapidly becomes cost-effective."

The ballpark estimates now merit more rigorous analysis, he said, and this will likely entail a multi-center study in the province.

However, he also noted that the many centers in Quebec use different PCR assays for C. diff, so there may be a need to adopt a uniform PCR testing strategy in the future.

The researchers currently use the Becton Dickinson GeneOhm PCR test for screening at the Quebec Heart and Lung Institute because that test was originally developed in Quebec City at Université Laval, by Longtin's colleague Michel Bergeron, founder of GenePOC Diagnostics.

The C. diff PCR test was the basis for Bergeron to set up a company called Infectio Diagnostics, which was acquired by GeneOhm and, in turn, purchased by BD, Longtin said.

"We know this test very well in Quebec City because many of the developers of this test still work at the infectious disease institute — we have very good insight into the capacity of this test, level of detection, and analytical performance," he said, adding that when BD brought the test to market in 2009 it was a "no brainer" for his group to begin using it to diagnose C. diff infections.

Longtin pointed out that BD had no involvement with the current study, and actually only learned about it when it was published last week.

In the future, however, the group may be shopping around and may need to begin discussions with commercial suppliers.

If so, they will have many options. There are a number of PCR-based C. diff tests approved by the US Food and Drug Administration for diagnosing active infection, including ones from Cepheid, Roche, Meridian, Nanosphere, Great Basin, Quest, Qiagen, and Quidel.

There are also C. diff tests reportedly in development from firms such as Hibergene, Alere, Mobidiag, Luminex, Lucigen, and Beckman Coulter. GenePOC also plans to launch a C. diff test this year.

In general, hospitals are increasingly using single platforms to conduct many PCRs, so C. diff test purchasing may be influenced by whatever platform they have in house, Longtin said.

It is also important to note that none of the commercially available tests is explicitly approved — by Health Canada or by the FDA — for screening asymptomatic carriers, so this continues to be an "off label" use, Longtin said.

The actual specificity and sensitivity of the BD test for diagnosing asymptomatic carriers is therefore not known, although the rate of carriers seen in Longtin's study is similar to a previous study in Quebec that used toxigenic culture.

The idea that doing better medicine might also save money was particularly notable to Longtin.

"Very often, you can provide better care, but it costs a bit more, and then you have the challenge of having to determine whether the extra cost is worth the benefit." He pointed out that there are usually fewer hurdles to implementation in a situation where improved care happens to be less expensive as well.

At least one test maker has already taken note of the Quebec study. Cepheid's CEO John Bishop discussed the work at some length in the firm's first quarter earnings call last week, suggesting, while there is still debate about molecular testing for hospital-acquired infections, it lends confidence to the belief that the HAI market will grow in the future.

Implementation of HAI screening, in particular, could be a boon for patients as well as diagnostics manufacturers. Screening for methicillin-resistant Staphylococcus aureus, for example, has been shown in one study to lead to a 70 percent reduction in infection while reducing overall healthcare cost by about $2 million per year.

On the other hand, other studies have suggested that molecular testing of patients with diarrhea and suspected C. diff may pick up carriers, essentially misdiagnosing patients whose illness is caused by other factors. And, increased use of more sensitive molecular testing methods may lead to an increase the C. diff burden estimates, according to an evaluation by the US Centers for Disease Control and Prevention. This could be particularly problematic if infection rates impact a hospital's funding.

"Many companies have set up [molecular] tests for diagnostic purposes, and in that context it is true that maybe PCR is too sensitive," Longtin said, "But for detecting asymptomatic carriers, you need to have a very sensitive, rapid test." He estimated that the volume of sales for asymptomatic screening would be in the range of 10-fold greater than sales for diagnostic purposes, which "may be a game changer for diagnostic companies."

Rectal screening uses a long cotton swab which is inserted three to four centimeters into the rectum and must be visibly soiled for PCR testing. Occasionally patients refused to be tested, and were then isolated, but the testing is becoming more acceptable, Longtin said. "They understand the purpose is to protect themselves and to protect other patients from acquiring a dangerous microbe in the hospital."

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