Poor yield of  Clostridium difficile  testing algorithms using glutamate dehydrogenase antigen and  C. difficile  toxin enzyme immunoassays in a pediatric population with declining prevalence of clostridium difficile strain BI/NAP1/027

Gomez, Emily J.; Montgomery, Sandra; Alby, Kevin; Robinson, Diana P.; Roundtree, Sylvester S.; Blecker-Shelly, Deborah; Sullivan, Kaede V.

doi:10.1016/j.diagmicrobio.2018.02.016

Cited by 10 publications

(4 citation statements)

References 19 publications

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“…Discrepancies in performance characteristics for the same C. difficile toxin and PCR assays have furthermore been observed to occur between different geographic sites and strain types [2,14,15], potentially contributing to our observed results. The low sensitivity of the rapid GDH/toxin combination at our institution is described in other studies, though it contrasts with the performance found by others [10,[16][17][18][19], a trend which remained consistent throughout this four-year study period. Our results were similar to those described in a cancer center patient population, in which an AUC of 0.83 was obtained with a Youden cutoff of ≤28.0 cycles (vs. our Youden cutoff of ≤27.8 cycles) for the prediction of CCNA toxin results.…”

Section: Discussioncontrasting

confidence: 82%

“…However, the actual value of its prognostic contribution, as compared to the information derived from toxin testing and assessment of clinical risk factors, has been questioned [24]. With different case definitions and specimen inclusion criteria between different studies, optimal cutoffs for tcdB C t values from the Xpert platform have ranged from <23.5 to <27.55 for predicting poor outcomes for CDI [9,19,[24][25][26][27]. Incorporating expert clinical consensus, a more recent study found a threshold of <24.0 cycles on the Xpert assay corresponded with a high probability of CDI [28].…”

Section: Discussionmentioning

confidence: 99%

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Clostridioides difficile Toxin B PCR Cycle Threshold as a Predictor of Toxin Testing in Stool Specimens from Hospitalized Adults

Lee

Nanda²,

Yamaguchi³

et al. 2022

Antibiotics

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Rapid, accurate detection of Clostridioides difficile toxin may potentially be predicted by toxin B PCR cycle threshold (tcdB Ct). We investigated the validity of this approach in an inpatient adult population. Patients who tested positive by C. difficile PCR (Cepheid GeneXpert) from December 2016 to October 2020 (n = 368) at a tertiary medical center were included. All stool samples were further tested by rapid glutamate dehydrogenase (GDH)/toxin B EIA and cell cytotoxin neutralization assay (CCNA). Receiver operating characteristic curves were analyzed. The area under the curve for tcdB Ct predicting toxin result by EIA was 0.795 (95% confidence interval (CI) 0.747–0.843) and by CCNA was 0.771 (95% CI 0.720–0.822). The Youden Ct cutoff for CCNA was ≤27.8 cycles (sensitivity 65.0%, specificity 77.2%). For specimens with Ct ≤ 25.0 cycles (n = 115), CCNA toxin was positive in >90%. The negative predictive value of tcdB Ct for CCNA was no greater than 80% regardless of cutoff chosen. In summary, very low Ct values (≤25.0) could have limited value as a rapid indicator of positive toxin status by CCNA in our patient population. A broad distribution of Ct values for toxin-negative and toxin-positive specimens precluded more robust prediction. Additional data are needed before broader application of Ct values from qualitatively designed assays to clinical laboratory reporting.

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Section: Discussioncontrasting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Clostridioides difficile Toxin B PCR Cycle Threshold as a Predictor of Toxin Testing in Stool Specimens from Hospitalized Adults

Lee

Nanda²,

Yamaguchi³

et al. 2022

Antibiotics

View full text Add to dashboard Cite

show abstract

“…Another reason may be the different prevalent strains in different regions or settings. For example, toxin-hyperproducing NAP1 strains are more often associated with toxin-positive results (24). Given the low sensitivity of EIA, additional tests such as the Nucleic Acid Amplification Test (NAAT) should be performed when CDI is suspected, but the EIA is negative (25).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Two Rapid Diagnostic Clostridioides difficile Infection Tests in a Chinese Hospital: A Real-world Analysis

Huang

Zhou

et al. 2022

Jundishapur J Microbiol

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Background: Accurate diagnosis is essential for optimal prevention and treatment of Clostridioides difficile infection (CDI), and various diagnostic methods must be evaluated. Objectives: We aimed to evaluate and compare the performance of VIDAS C. difficile, C. DIFF QUIK CHEK COMPLETE (QCC), and toxigenic culture (TC) tests for diagnosing CDI and further determine the relationships between clinical factors and the toxin status of patients. Methods: Stool samples were randomly selected for VIDAS or QCC testing according to the manufacturer’s instructions between May 2017 and May 2021, and their performance was compared with that of TC. Clinical information was obtained from the hospital’s electronic medical records. Results: Among 10,897 samples tested, 6,435 and 4,462 samples were assigned for VIDAS and QCC tests, respectively. A total of 9.1% (996/10,897) of the samples were positive for TC. The sensitivity, specificity, positive predictive value, and negative predictive value were 36.6%, 98.6%, 72.1%, and 87.6% for VIDAS toxins A and B testing and 31.6%, 98.2%, 64.0%, and 87.8% for QCC toxin testing, respectively. Our results showed that the clinical data of the patients with positive and detectable toxins were not significantly different. Conclusions: The VIDAS and QCC tests provide rapid screening assays for the laboratory diagnosis of CDI. However, a more specific test to detect free toxins is required to confirm the diagnosis for glutamate dehydrogenase (GDH)-positive and toxin-negative samples. The clinical characteristics and outcomes of this cohort were similar, regardless of the results of toxins A and B testing.

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“…Furthermore, rapid diagnosis of CDI with NAAT alone was more timely and accurate, and correlated better with clinical diagnosis [ 13 ]. In another study among pediatric patients, the sensitivity of a NAAT alone algorithm was 94% versus 85% for the GDH/toxin algorithm, suggesting that GDH-based algorithms can result in more false negative or missed CDI diagnoses [ 14 ]. In addition to diagnostic inaccuracy, evidence suggests that CDI has been underdiagnosed in Japan by up to 24% based on current practice [ 15 , 16 ], where GDH/toxin is the first-line test for CDI.…”

Section: Introductionmentioning

confidence: 99%

Budget Impact Analysis of Adopting a One-Step Nucleic Acid Amplification Testing (NAAT) Alone Diagnostic Pathway for Clostridioides difficile in Japan Compared to a Two-Step Algorithm with Glutamate Dehydrogenase/Toxin Followed by NAAT

Lim¹,

Tomaru²,

Chua

et al. 2023

Diagnostics

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Clostridioides difficile infection (CDI) is a major healthcare-associated infection that leads to a significant health economic burden in Japan. Using a decision tree model, we evaluated the budget impact of adopting a one-step nucleic acid amplification test (NAAT) alone pathway compared to a two-step diagnostic algorithm with glutamate dehydrogenase (GDH) and toxin antigen, followed by NAAT. The analysis was conducted from the government payer’s perspective for 100,000 symptomatic, hospitalized adults requiring a CDI diagnostic test. One-way sensitivity analysis was conducted for all data inputs. The NAAT alone strategy costed JPY 225,886,360 (USD 2,424,714) more, but was more effective, resulting in 1749 more patients accurately diagnosed and 91 fewer deaths compared to the two-step algorithm. Additionally, the NAAT alone pathway costed JPY 26,146 (USD 281) less per true positive CDI diagnosed. The total budget impact, and cost per CDI diagnosed was most sensitive to GDH sensitivity in one-way sensitivity analysis, where a lower GDH sensitivity resulted in greater cost savings with the NAAT alone pathway. Findings from this budget impact analysis can guide the adoption of a NAAT alone pathway for CDI diagnosis in Japan.

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Poor yield of Clostridium difficile testing algorithms using glutamate dehydrogenase antigen and C. difficile toxin enzyme immunoassays in a pediatric population with declining prevalence of clostridium difficile strain BI/NAP1/027

Cited by 10 publications

References 19 publications

Clostridioides difficile Toxin B PCR Cycle Threshold as a Predictor of Toxin Testing in Stool Specimens from Hospitalized Adults

Clostridioides difficile Toxin B PCR Cycle Threshold as a Predictor of Toxin Testing in Stool Specimens from Hospitalized Adults

Evaluation of Two Rapid Diagnostic Clostridioides difficile Infection Tests in a Chinese Hospital: A Real-world Analysis

Budget Impact Analysis of Adopting a One-Step Nucleic Acid Amplification Testing (NAAT) Alone Diagnostic Pathway for Clostridioides difficile in Japan Compared to a Two-Step Algorithm with Glutamate Dehydrogenase/Toxin Followed by NAAT

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