Asymptomatic carriage of toxigenic Clostridium difficile by hospitalized patients

Guerrero, Dubert M.; Becker, Juergen C.; Eckstein, Elizabeth C.; Kundrapu, Sirisha; Deshpande, Abhishek; Sethi, Ajay K.; Donskey, Curtis J.

doi:10.1016/j.jhin.2013.07.002

Cited by 68 publications

(44 citation statements)

References 10 publications

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“…The studies in asymptomatically colonized patients vary greatly in patient inclusion criteria, tested material, and applied diagnostic and gold standard tests. For instance, a great number of the studies only test rectal swabs or use a combination of stool samples and rectal swabs (4,8,18,22,23,31,34). Guerrero et al showed that asymptomatic carriers have lower numbers of C. difficile in their rectal swab than CDI patients, indicating that stool samples should be preferred (4).…”

Section: Discussionmentioning

confidence: 99%

“…For instance, a great number of the studies only test rectal swabs or use a combination of stool samples and rectal swabs (4,8,18,22,23,31,34). Guerrero et al showed that asymptomatic carriers have lower numbers of C. difficile in their rectal swab than CDI patients, indicating that stool samples should be preferred (4). Furthermore, a mix of diagnostic screening tests have been applied to detect C. difficile, frequently subdivided into assays to recognize toxigenic or nontoxigenic strains (20).…”

Section: Discussionmentioning

confidence: 99%

“…Asymptomatic colonization of C. difficile varies widely between various patient populations studied. Approximately 5 to 15% of newly hospital admitted patients carry C. difficile in their feces (4,5,(14)(15)(16)(17). Carriage rates of residents in long-term-care facilities vary from 4 to 51% but in general tend to be higher than in hospitalized patients (3,14,18).…”

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confidence: 99%

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

et al. 2017

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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-

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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

et al. 2017

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“…In addition, carriers can have diarrhea due to other causes, such as norovirus gastroenteritis, tube feedings, laxatives, antibiotics, or other causes, and toxigenic C. difficile is merely a bystander (14,15). Carriers have been increasingly recognized in asymptomatic individuals of all ages, including 10% or more of hospitalized patients and up to 51% of patients in a long-term-care facility (16)(17)(18)(19)(20)(21). Attempting to eradicate carriage by treating with antibiotics may have adverse effects on the host-pathogen balance, increasing the risk of subsequent diarrhea, and is not currently recommended (1,16,22,23).…”

Section: Discussionmentioning

confidence: 99%

“…Instead, they recommend a new diagnostic category of C. difficile excretor for carriers whose diarrhea is probably not due to CDI but who can potentially transmit infection. It has been postulated that even asymptomatic carriers are a cause of nosocomial transmission and should be placed in isolation (21,26,27). A recent study used genotyping to investigate the role of asymptomatic carriers in transmission in a ward and concluded that carriers played an important role (27).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Simplexa Universal Direct PCR with Cytotoxicity Assay for Diagnosis of Clostridium difficile Infection: Performance, Cost, and Correlation with Disease

2014

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Simplexa Clostridium difficile universal direct PCR, a real-time PCR assay for the detection of the C. difficile toxin B (tcdB) gene using the 3M integrated cycler, was compared with a two-step algorithm which includes the C. Diff Chek-60 glutamate dehydrogenase (GDH) antigen assay followed by cytotoxin neutralization. Three hundred forty-two liquid or semisolid stools submitted for diagnostic C. difficile testing, 171 GDH antigen positive and 171 GDH antigen negative, were selected for the study. All samples were tested by the C. Diff Chek-60 GDH antigen assay, cytotoxin neutralization, and Simplexa direct PCR. Of 171 GDHpositive samples, 4 were excluded (from patients on therapy or from whom duplicate samples were obtained) and 88 were determined to be true positives for toxigenic C. difficile. Of the 88, 67 (76.1%) were positive by the two-step method and 86 (97.7%) were positive by PCR. Seventy-nine were positive by the GDH antigen assay only. Of 171 GDH antigen-negative samples, none were positive by PCR. One antigen-negative sample positive by the cytotoxin assay only was deemed a false positive based on chart review. Simplexa C. difficile universal direct PCR was significantly more sensitive for detecting toxigenic C. difficile bacteria than cytotoxin neutralization (P ‫؍‬ 0.0002). However, most PCR-positive/cytotoxin-negative patients did not have clear C. difficile disease. The estimated cost avoidance provided by a more rapid molecular diagnosis was outweighed by the cost of isolating and treating PCR-positive/cytotoxin-negative patients. The costs, clinical consequences, and impact on nosocomial transmission of treating and/or isolating patients positive for toxigenic C. difficile by PCR but negative for in vivo toxin production merit further study. Clostridium difficile infection (CDI) is a major cause of nosocomial diarrhea, leading to morbidity and mortality in hospitalized patients (1). Anaerobic culture and bacterial glutamate dehydrogenase (GDH) antigen tests detect the presence of both nontoxigenic and toxigenic strains of C. difficile. Toxigenic culture and PCR for toxin genes detect only the presence of bacteria capable of making toxin; these tests cannot separate active disease from colonization. Tests for toxin production in vivo, e.g., enzyme-linked immunosorbent assay (ELISA) to detect toxins in stool specimens or cell culture to determine cytotoxicity, have been considered insensitive compared to molecular methods (2). In a previous report, we compared our two-step C. difficile algorithm testing for GDH antigen and cytotoxin to one of the first commercially available PCR tests (3). While PCR was significantly more sensitive than toxin ELISA, its results were not statistically different from those of the two-step algorithm, it failed to detect nine cytotoxin-positive stools, and it was more expensive. Furthermore, patients positive by PCR but not for cytotoxin did not appear to have C. difficile disease.The objective of this study was to compare the performance of the newly available Simp...

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Hospital Ward Antibiotic Prescribing and the Risks ofClostridium difficileInfection

et al. 2015

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IMPORTANCE Only a portion of hospital-acquired Clostridium difficile infections can be traced back to source patients identified as having symptomatic disease. Antibiotic exposure is the main risk factor for C difficile infection for individual patients and is also associated with increased asymptomatic shedding. Contact with patients taking antibiotics within the same hospital ward may be a transmission risk factor for C difficile infection, but this hypothesis has never been tested. OBJECTIVES To obtain a complete portrait of inpatient risk that incorporates innate patient risk factors and transmission risk factors measured at the hospital ward level and to investigate ward-level rates of antibiotic use and C difficile infection risk.

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Asymptomatic carriage of toxigenic Clostridium difficile by hospitalized patients

Cited by 68 publications

References 10 publications

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

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

Comparison of Simplexa Universal Direct PCR with Cytotoxicity Assay for Diagnosis of Clostridium difficile Infection: Performance, Cost, and Correlation with Disease

Hospital Ward Antibiotic Prescribing and the Risks ofClostridium difficileInfection

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