Clinical heterogeneity of patients with stool samples testing PCR+/Tox− from a two-step Clostridium difficile diagnostic algorithm

Zou, Jason; Leung, Victor; Champagne, Sylvie; Hinch, Michelle; Wong, Anna; Lloyd‐Smith, Elisa; Nguyen, Trong Tien; Romney, Marc G.; Sharma, Azra; Payne, Michael; Lowe, Christopher F.

doi:10.1007/s10096-018-3383-7

Cited by 18 publications

(20 citation statements)

References 16 publications

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“…This is similar to what has been shown in a cohort of 125 PCR ϩ /EIA Ϫ patients in Spain, where 4.8% had CDI-related complications and an additional 4.8% died due to CDI (7). It is also comparable to a study from Canada in which the proportion of patients with CDIrelated complications was 9% among 110 PCR ϩ /EIA Ϫ patients (8). ESCMID guidelines nicely highlight this problem, in which PCR ϩ /EIA Ϫ results may indicate carriage or true disease (11).…”

Section: Discussionsupporting

confidence: 88%

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Predictors of Clostridioides difficile Infection-Related Complications and Treatment Patterns among Nucleic Acid Amplification Test-Positive/Toxin Enzyme Immunoassay-Negative Patients

et al. 2020

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The addition of toxin enzyme immunoassay (EIA) to nucleic acid amplification tests, including PCR, creates challenges in the diagnosis and management of Clostridioides difficile infection (CDI). There are limited data in large cohorts, with discordant results, that is, PCR-positive/EIA-negative (PCR+/EIA−) results. We conducted a retrospective cohort study on all PCR+/EIA− adult inpatients and assessed CDI-related complications and clinical failure. We identified 240 individuals. Twenty-three (9.6%) patients experienced a CDI-related complication, including 2 cases of megacolon, 1 colectomy, and 22 intensive care unit (ICU) admissions. In multivariable logistic regression analyses, baseline severe disease by Infectious Diseases Society of America (IDSA) criteria (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.88 to 18.1; P = 0.002), baseline fulminant colitis (OR, 84.7; 95% CI, 14.3 to 500; P < 0.001), fever of >38.5°C (OR, 4.61; 95% CI, 1.42 to 15.0; P = 0.011), and proton pump inhibitor (PPI) use (OR, 3.50; 95% CI, 1.19 to 10.3; P = 0.023) were associated with increased odds of CDI-related complications. For 67 PCR+/EIA− patients who did not receive complete treatment, clinical failure was observed in 10 (15%) patients. A comparison of PCR+/EIA− patients who received complete treatment to all 112 PCR+/EIA+ patients showed no differences in CDI-related complications (11% and 13% for PCR+/EIA− and PCR+/EIA+ patients, respectively), 60-day all-cause mortality (17% and 18% for PCR+/EIA− and PCR+/EIA+ patients, respectively), or recurrent CDI (7% and 9% for PCR+/EIA− and PCR+/EIA+ patients, respectively). Predictors of CDI-attributable complications among PCR+/EIA− patients include baseline severe disease by IDSA criteria, baseline fulminant colitis, and fever of >38.5°C. Identifying the subgroup of PCR+/EIA− patients who could have true disease, and therefore allowing them to be targeted for treatment, is critical.

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Section: Discussionsupporting

confidence: 88%

“…It has been shown that patients with negative EIA results tend to develop less severe forms of CDI or no CDI at all (3,7). However, it has also been shown that severe CDI can develop in PCR ϩ /EIA Ϫ patients (8)(9)(10).…”

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confidence: 99%

Predictors of Clostridioides difficile Infection-Related Complications and Treatment Patterns among Nucleic Acid Amplification Test-Positive/Toxin Enzyme Immunoassay-Negative Patients

et al. 2020

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“…The PCR tests are very sensitive to C. difficile but do not distinguish between symptomatic CDI and asymptomatic colonization, as they determine the genes for the production of toxins [ 9 ]. Genetic evidence of the toxigenic strain does not automatically mean that toxins are produced [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Methods of Clostridioides difficile Infection and Clostridioides difficile Ribotypes in Studied Sample

et al. 2021

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Background: Clostridioides (Clostridium) difficile is the most common nosocomial pathogen and antibiotic-related diarrhea in health-care facilities. Over the last few years, there was an increase in the incidence rate of C. difficile infection cases in Slovakia. In this study, the phenotypic (toxigenicity, antimicrobial susceptibility) and genotypic (PCR ribotypes, genes for binary toxins) patterns of C. difficile isolates from patients with CDI were analyzed, from July to August 2016, taken from hospitals in the Horne Povazie region of northern Slovakia. The aim of the study was also to identify hypervirulent strains (e.g., the presence of RT027 or RT176). Methods: The retrospective analysis of biological samples suspected of CDI were analyzed by GDH, anaerobic culture, enzyme immunoassay on toxins A/B, multiplex “real-time” PCR and PCR capillary-based electrophoresis ribotyping, and by MALDI TOF MS. Results: C. difficile isolates (n = 44) were identified by PCR ribotyping, which revealed five different ribotypes (RT001, 011, 017, 081, 176). The presence of hypervirulent RT027 was not identified. The C. difficile isolates (RT001, 011, 081, 176) were susceptible to metronidazole and vancomycin. One isolate RT017 had reduced susceptibility to vancomycin. A statistically significant difference between the most prevalent PCR ribotypes, RT001 and RT176, regarding variables such as albumin, CRP, creatinine, the length of hospitalization (p = 0.175), and glomerular filtration (p = 0.05) was not found. Conclusion: The results of PCR capillary-based electrophoresis ribotyping in the studied samples showed a high prevalence of RT176 and 001.

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“…Data collected in the chart review included clinical history, symptoms, vital signs, laboratory data (WBC, creatinine), alternative reasons for diarrhoea (laxative use within 48 hours of testing, nasogastric tube or enteral feed, current chemotherapy), type of ordering clinician and C. difficile test results. C. difficile testing at our laboratory is based on the reverse algorithm as previously described [5] . Rejection criteria included testing only unformed stool samples.…”

Section: Methodsmentioning

confidence: 99%

Prospective Review of Clostridioides difficile Testing Indications to Inform Local Laboratory Stewardship Initiatives

Reich

Payne

Sharma

et al. 2019

Infection Prevention in Practice

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Summary We conducted a prospective chart review to determine the prevalence of and reasons for inappropriate Clostridioides difficile test-ordering at a tertiary care hospital. Inappropriate orders accounted for 54% of all tests. The two primary aetiologies of inappropriate test-ordering were an alternative reason for diarrhoea (34%) and an asymptomatic patient (20%). These results highlight the need to focus diagnostic stewardship of C. difficile testing on pre-analytical factors.

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Clinical heterogeneity of patients with stool samples testing PCR+/Tox− from a two-step Clostridium difficile diagnostic algorithm

Cited by 18 publications

References 16 publications

Predictors of Clostridioides difficile Infection-Related Complications and Treatment Patterns among Nucleic Acid Amplification Test-Positive/Toxin Enzyme Immunoassay-Negative Patients

Predictors of Clostridioides difficile Infection-Related Complications and Treatment Patterns among Nucleic Acid Amplification Test-Positive/Toxin Enzyme Immunoassay-Negative Patients

Diagnostic Methods of Clostridioides difficile Infection and Clostridioides difficile Ribotypes in Studied Sample

Prospective Review of Clostridioides difficile Testing Indications to Inform Local Laboratory Stewardship Initiatives

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