Detection of Clostridium difficile in Feces of Asymptomatic Patients Admitted to the Hospital

Abstract

Recent evidence shows that patients asymptomatically colonized with Clostridium difficile may contribute to the transmission of C. difficile in health care facilities. Additionally, these patients may have a higher risk of developing C. difficile infection. The aim of this study was to compare a commercially available PCR directed to both toxin A and B (artus C. difficile QS-RGQ kit CE; Qiagen), an enzymelinked fluorescent assay to glutamate dehydrogenase (GDH ELFA) (Vidas, bioMéri-eux), and an in-house-developed PCR to tcdB, with (toxigenic) culture of C. difficile as the gold standard to detect asymptomatic colonization. Test performances were evaluated in a collection of 765 stool samples obtained from asymptomatic patients at admission to the hospital. The C. difficile prevalence in this collection was 5.1%, and 3.1% contained toxigenic C. difficile. Compared to C. difficile culture, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the C. difficile GDH ELFA were 87.2%, 91.2%, 34.7%, and 99.3%, respectively. Compared with results of toxigenic culture, the sensitivity, specificity, PPV, and NPV of the commercially available PCR and the in-house PCR were 95.8%, 93.4%, 31.9%, 99.9%, and 87.5%, 98.8%, 70%, and 99.6%, respectively. We conclude that in a lowprevalence setting of asymptomatically colonized patients, both GDH ELFA and a nucleic acid amplification test can be applied as a first screening test, as they both display a high NPV. However, the low PPV of the tests hinders the use of these assays as stand-alone tests.KEYWORDS Clostridium difficile, asymptomatic, carrier, diagnostics C lostridium difficile infection (CDI) is a leading cause of hospital-acquired diarrhea. The transmission of spores from symptomatic patients can spread C. difficile within health care facilities, with a subsequent development of more symptomatic patients and eventually clusters and outbreaks. However, recent data suggest that patients asymptomatically colonized with C. difficile also contribute to the spread of C. difficile spores to the environment and to other patients (1-3). Asymptomatic carriers shed spores into the environment to a lesser extent than CDI patients (3, 4), but by outnumbering the CDI patients, they can still play an important role in the transmission of the disease. This hypothesis has recently been supported in a Canadian study, where isolation of C. difficile-colonized patients significantly reduced the incidence of hospitalacquired CDI (5). A second new insight into the significance of asymptomatic colonization is that it may increase the risk of subsequent clinical disease in some colonized patients (6-10). Progression from colonization to CDI can be provoked by alterations of the microbiota and a subsequent decrease in secondary bile acids, which normally inhibit spore germination (11-13). But other factors, like preexisting antitoxin antibod-

Laboratory Testing of Donors and Stool Samples for Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection

“…Commercial nucleic acid testing has previously been shown to have a higher negative predictive value in testing symptomatic patients than that with a glutamate dehydrogenase (GDH) or multistep testing algorithm (27). However, a recent study of detection of C. difficile in asymptomatic patients suggested a very similar negative predictive value of GDH compared to a commercial nucleic acid amplification test (NAAT) (99.3% versus 99.9%, respectively) (28). Most clinical laboratories that will be screening donor stool are likely committed to one of these testing strategies for symptomatic patients, and these data suggest that GDH or NAAT is likely to be appropriate.…”

Pediatric oncology and stem cell transplant patients with healthcare‐associated Clostridium difficile infection were already colonized on admission

“…The asymptomatic colonization rate of toxigenic C. difficile in hospitalized adult patients was found to range from 3% to 20%, but this is higher (24%–55%) in infants and young children …”

Validation of Active Surveillance Testing for Clostridium difficile Colonization Using the cobas Cdiff Test

“…However, there was no information provided on the analytical performance of the real-time PCR assay they used when applied to rectal surveillance swabs. Terveer et al also examined the suitability of PCR to detect asymptomatic colonization (14). In this study, swabs inserted into the stool were tested using a real-time PCR test as well as by an enzyme-linked fluorescent assay (ELFA) detecting glutamate dehydrogenase (14).…”

“…Terveer et al also examined the suitability of PCR to detect asymptomatic colonization (14). In this study, swabs inserted into the stool were tested using a real-time PCR test as well as by an enzyme-linked fluorescent assay (ELFA) detecting glutamate dehydrogenase (14). As expected, the real-time PCR test outperformed the ELFA, with the sensitivity and specificity of the real-time PCR being 96% and 93%, respectively, while the ELFA had a sensitivity and specificity of 87% and 91% (14).…”