scholarly journals Strategies for Optimizing the Diagnostic Predictive Value of Clostridium difficile Molecular Diagnostics

2017 ◽  
Vol 55 (5) ◽  
pp. 1244-1248 ◽  
Author(s):  
Larry K. Kociolek
Keyword(s):  
Clostridium Difficile ◽  
Predictive Value ◽  
Clinical Microbiology ◽  
Nucleic Acid Amplification ◽  
Oral Vancomycin ◽  
Content Type ◽  
Clinical Bioinformatics ◽  
Laxative Use ◽  
Low Probability ◽  
Clinically Significant

ABSTRACT Because nucleic acid amplification tests (NAATs) do not distinguish Clostridium difficile infection (CDI) and asymptomatic C. difficile carriage, the diagnostic predictive value of NAATs is limited when used in patients with a low probability of CDI. In this issue of the Journal of Clinical Microbiology , Truong et al. (J. Clin. Microbiol., 55:1276–1284, 2017, https://doi.org/10.1128/JCM.02319-16 ) report significant reductions in hospital-onset CDI and oral vancomycin utilization at their institution following implementation of a novel intervention that leveraged their clinical bioinformatics resources to prevent C. difficile testing of stools from patients without clinically significant diarrhea and in patients with recent laxative use.

scholarly journals Clostridium difficile Laboratory Identification Event Reporting – A Need for Diagnostic Stewardship

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S398-S399
Author(s):  
Clare Rock ◽  
Zoi Pana ◽  
Surbhi Leekha ◽  
Polly Trexler ◽  
Jennifer Andonian ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Medical Records ◽  
Chart Review ◽  
Nucleic Acid Amplification ◽  
Event Reporting ◽  
Laxative Use ◽  
Academic Center ◽  
The Us ◽  
Clinically Significant ◽  
Present On Admission

Abstract Background Clostridium difficile LabID event reporting uses electronic laboratory results without chart review. Nucleic acid amplification testing is common in the US. A positive result may represent colonization or C. diff infection (CDI). We review C.difflabID events to ascertain if Hospital-Onest CDI (HO CDI). For non-HO CDI, we identify reason and use a matrix to prioritize clinical areas for intervention efforts. Methods Each C. difflab ID event from Jan 2015 to June 2016 at academic center had chart review for HO CDI; defined significant diarrhea, not present on admission, with no laxatives in prior 48 hours. For non HO-CDI events, reason and receipt of antibiotic treatment within 14 days of the positive test were retrospectively noted. A prioritization matrix, where clinical services were ranked according to number of lab ID events (service’s contribution to the facility C. diffLabID), was multiplied by a rank based on percent of inappropriate tests giving an overall prioritization score for where intervention resources could potentially best be used. Results There were 490 C difficile LabID events; 284 (58%) were HO-CDI; 206 (42%) were inappropriate or delayed testing. Of the 190 with available medical records at time of retrospective review, reasons for not meeting the HO-CDI included laxative use within the previous 48 hours (41%), no clinically significant diarrhea (49.5%); delayed testing (9.5%). See figure. Of 172 patients with inappropriate testing, 159 (92%) were treated for CDI. Medicine and psychiatry ranked first and second on prioritization matrix. See table. Conclusion Nearly half of C. diff LabID events were not true HO CDI, but inappropriate or delayed tests. Prioritization matrix identified medicine and psychiatry as areas where diagnostic stewardship interventions could affect most on facility C. diff LabID. Disclosures K. C. Carroll, GenePOC, Inc.: Grant Investigator, Grant recipient

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

2016 ◽  
Vol 55 (2) ◽  
pp. 403-411 ◽  
Author(s):  
Elisabeth M. Terveer ◽  
Monique J. T. Crobach ◽  
Ingrid M. J. G. Sanders ◽  
Margreet C. Vos ◽  
Cees M. Verduin ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Predictive Value ◽  
Health Care Facilities ◽  
Nucleic Acid Amplification ◽  
Content Type ◽  
Asymptomatic Patients ◽  
Toxigenic Culture ◽  
Stool Samples ◽  
Sensitivity Specificity ◽  
Low Prevalence

ABSTRACTRecent evidence shows that patients asymptomatically colonized withClostridium difficilemay contribute to the transmission ofC. difficilein health care facilities. Additionally, these patients may have a higher risk of developingC. difficileinfection. The aim of this study was to compare a commercially available PCR directed to both toxin A and B (artusC. difficileQS-RGQ kit CE; Qiagen), an enzyme-linked fluorescent assay to glutamate dehydrogenase (GDH ELFA) (Vidas, bioMérieux), and an in-house-developed PCR totcdB, with (toxigenic) culture ofC. difficileas 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. TheC. difficileprevalence in this collection was 5.1%, and 3.1% contained toxigenicC. difficile. Compared toC. difficileculture, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of theC. difficileGDH 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 low-prevalence 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.

scholarly journals Evaluation of the QiagenartusC. difficile QS-RGQ Kit for Detection of Clostridium difficile Toxins A and B in Clinical Stool Specimens

2015 ◽  
Vol 53 (6) ◽  
pp. 1942-1944 ◽  
Author(s):  
Nathalie Jazmati ◽  
Pia Wiegel ◽  
Božica Ličanin ◽  
Georg Plum
Keyword(s):  
Nucleic Acid ◽  
Clostridium Difficile ◽  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Nucleic Acid Amplification Test ◽  
Nucleic Acid Amplification ◽  
Content Type ◽  
Stool Specimens ◽  
Sensitivity Specificity

We compared the QiagenartusC. difficile QS-RGQ kit, a new nucleic acid amplification test for the detection ofClostridium difficiletoxins in stool specimens, with the Cepheid XpertC. difficiletest. The sensitivity, specificity, positive predictive value, and negative predictive value for the QiagenartusC. difficile QS-RGQ test were 100%, 89.5%, 60.9%, and 100%, and those for the Cepheid XpertC. difficiletest were 100%, 90%, 62.2%, and 100%, respectively.

scholarly journals Infection with Toxin A-Negative, Toxin B-Negative, Binary Toxin-Positive Clostridium difficile in a Young Patient with Ulcerative Colitis

2015 ◽  
Vol 53 (11) ◽  
pp. 3702-3704 ◽  
Author(s):  
Grace O. Androga ◽  
Julie Hart ◽  
Niki F. Foster ◽  
Adrian Charles ◽  
David Forbes ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Clostridium Difficile ◽  
Young Patient ◽  
Diagnostic Methods ◽  
Binary Toxin ◽  
Toxin A ◽  
Toxin B ◽  
Content Type ◽  
Severe Diarrhea ◽  
Clinically Significant

Large clostridial toxin-negative, binary toxin-positive (A−B−CDT+) strains ofClostridium difficileare almost never associated with clinically significantC. difficileinfection (CDI), possibly because such strains are not detected by most diagnostic methods. We report the isolation of an A−B−CDT+ribotype 033 (RT033) strain ofC. difficilefrom a young patient with ulcerative colitis and severe diarrhea.

scholarly journals Nucleic Acid Amplification Test Quantitation as Predictor of Toxin Presence in Clostridium difficile Infection

2017 ◽  
Vol 56 (3) ◽  
Author(s):  
M. J. T. Crobach ◽  
N. Duszenko ◽  
E. M. Terveer ◽  
C. M. Verduin ◽  
E. J. Kuijper
Keyword(s):  
Nucleic Acid ◽  
Clostridium Difficile ◽  
Characteristic Curve ◽  
Nucleic Acid Amplification Test ◽  
Nucleic Acid Amplification ◽  
Toxin A ◽  
Toxin B ◽  
Content Type ◽  
Quantitative Results ◽  
Testing Algorithm

ABSTRACT Multistep algorithmic testing in which a sensitive nucleic acid amplification test (NAAT) is followed by a specific toxin A and toxin B enzyme immunoassay (EIA) is among the most accurate methods for Clostridium difficile infection (CDI) diagnosis. The obvious shortcoming of this approach is that multiple tests must be performed to establish a CDI diagnosis, which may delay treatment. Therefore, we sought to determine whether a preliminary diagnosis could be made on the basis of the quantitative results of the first test in algorithmic testing, which provide a measure of organism burden. To do so, we retrospectively analyzed two large collections of samples ( n = 2,669 and n = 1,718) that were submitted to the laboratories of two Dutch hospitals for CDI testing. Both hospitals apply a two-step testing algorithm in which a NAAT is followed by a toxin A/B EIA. Of all samples, 208 and 113 samples, respectively, tested positive by NAAT. Among these NAAT-positive samples, significantly lower mean quantification cycle ( C q ) values were found for patients whose stool eventually tested positive for toxin, compared with patients who tested negative for toxin (mean C q values of 24.4 versus 30.4 and 26.8 versus 32.2; P < 0.001 for both cohorts). Receiver operating characteristic curve analysis was performed to investigate the ability of C q values to predict toxin status and yielded areas under the curve of 0.826 and 0.854. Using the optimal C q cutoff values, prediction of the eventual toxin A/B EIA results was accurate for 78.9% and 80.5% of samples, respectively. In conclusion, C q values can serve as predictors of toxin status but, due to the suboptimal correlation between the two tests, additional toxin testing is still needed.

scholarly journals Isolation of Campylobacter Species from Stool Samples by Use of a Filtration Method: Assessment from a United States-Based Population

2017 ◽  
Vol 55 (7) ◽  
pp. 2204-2207 ◽  
Author(s):  
Irving Nachamkin ◽  
Phi Nguyen
Keyword(s):  
United States ◽  
Clinical Microbiology ◽  
Clinical Microbiology Laboratory ◽  
Microbiology Laboratory ◽  
Filtration Method ◽  
Content Type ◽  
Stool Samples ◽  
Campylobacter Species ◽  
Clinically Significant ◽  
Microaerobic Conditions

ABSTRACT Fecal samples submitted to our clinical microbiology laboratory from patients in the Philadelphia region were prospectively analyzed for Campylobacter species other than C. jejuni and C. coli using a filtration method and microaerobic conditions with increased H 2 concentrations. Of 225 samples tested, 13 (5.8%) yielded Campylobacter species, with frequent isolation of C. concisus . The majority of Campylobacter species were not clinically significant. Additional studies in U.S. populations are warranted.

scholarly journals Development and Validation of Digital Enzyme-Linked Immunosorbent Assays for Ultrasensitive Detection and Quantification of Clostridium difficile Toxins in Stool

2015 ◽  
Vol 53 (10) ◽  
pp. 3204-3212 ◽  
Author(s):  
Linan Song ◽  
Mingwei Zhao ◽  
David C. Duffy ◽  
Joshua Hansen ◽  
Kelsey Shields ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Cytotoxicity Assay ◽  
Nucleic Acid Amplification ◽  
Analytical Sensitivity ◽  
Toxin B ◽  
Content Type ◽  
Toxigenic Culture ◽  
Immunosorbent Assays ◽  
Digital Elisa ◽  
Detection And Quantification

The currently available diagnostics forClostridium difficileinfection (CDI) have major limitations. Despite mounting evidence that toxin detection is paramount for diagnosis, conventional toxin immunoassays are insufficiently sensitive and cytotoxicity assays too complex; assays that detect toxigenic organisms (toxigenic culture [TC] and nucleic acid amplification testing [NAAT]) are confounded by asymptomatic colonization by toxigenicC. difficile. We developed ultrasensitive digital enzyme-linked immunosorbent assays (ELISAs) for toxins A and B using single-molecule array technology and validated the assays using (i) culture filtrates from a panel of clinicalC. difficileisolates and (ii) 149 adult stool specimens already tested routinely by NAAT. The digital ELISAs detected toxins A and B in stool with limits of detection of 0.45 and 1.5 pg/ml, respectively, quantified toxins across a 4-log range, and detected toxins from all clinical strains studied. Using specimens that were negative by cytotoxicity assay/TC/NAAT, clinical cutoffs were set at 29.4 pg/ml (toxin A) and 23.3 pg/ml (toxin B); the resulting clinical specificities were 96% and 98%, respectively. The toxin B digital ELISA was 100% sensitive versus cytotoxicity assay. Twenty-five percent and 22% of the samples positive by NAAT and TC, respectively, were negative by the toxin B digital ELISA, consistent with the presence of organism but minimal or no toxin. The mean toxin levels by digital ELISA were 1.5- to 1.7-fold higher in five patients with CDI-attributable severe outcomes, versus 68 patients without, but this difference was not statistically significant. Ultrasensitive digital ELISAs for the detection and quantification of toxins A and B in stool can provide a rapid and simple tool for the diagnosis of CDI with both high analytical sensitivity and high clinical specificity.

scholarly journals 2345. Reduction in Testing and Change in Testing Algorithm Associated with Decrease in Number of Nosocomial Clostridium difficile Infections

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S806-S806
Author(s):  
Susan Nichols ◽  
Michelle D Jordan ◽  
Michael Coogan ◽  
Jackie Opera ◽  
Paul P Cook
Keyword(s):  
Clostridium Difficile ◽  
Best Practice ◽  
Medical Center ◽  
Nucleic Acid Amplification ◽  
Antimicrobial Use ◽  
Continuous Variables ◽  
Laxative Use ◽  
Days Of Therapy ◽  
Before And After ◽  
Testing Algorithm

Abstract Background Previous data at our facility indicated 37% of patients with Clostridium difficile infection (CDI) were receiving at least one laxative at the time of testing, suggesting the possibility of false-positive results. Nucleic acid amplification testing (NAAT) does not distinguish between colonization and infection with C. difficile. We implemented two interventions to address these issues and evaluated our rates of nosocomial CDI before and after these changes. Methods This was a retrospective study of all positive test results for adult patients with nosocomial C. difficile from October 1, 2017 through March 31, 2019 at Vidant Medical Center, a 911-bed hospital. In June, 2018, we implemented a best practice advisory (BPA) in our electronic health record to recommend against testing for CDI in patients receiving laxatives. We reviewed the number of C. difficile tests ordered before and after initiating the BPA. In December, 2018, we removed NAAT and replaced it with a cell cytotoxicity assay (CCA) for specimens that were enzyme immunoassay (EIA) negative and glutamate dehydrogenase (GDH) positive. Antimicrobial use was measured in days of therapy (DOT) per 10,000 patient-days (PD). Mann–Whitney U test was used for continuous variables. Linear regression was used to monitor antimicrobial use. Results The number of C. difficile tests ordered per month decreased 19.5% after implementing the BPA (P < 0.0001). There was a 44% reduction in the number of EIA+/GDH+ specimens per month after the BPA intervention (P = 0.003). Following substitution of CCA for NAAT for EIA-/GDH+ specimens, there was a 61% reduction in the rate of nosocomial CDI (8.6 cases/10,000 PD to 3.3 cases/10,000 PD; P = 0.005). Total antimicrobial use was unchanged over the course of the study (673 to 677 DOT/10,000 PD). Carbapenem use decreased 56% (P = 0.009); cefepime use increased 85%(p = 0.002); quinolone and clindamycin use were unchanged. Conclusion Laxative use in hospitalized patients is common and likely contributes to a false elevation in the CDI rate by identifying carriers in addition to those who have true infection. Implementing a BPA to reduce inappropriate testing and changing our testing algorithm for Clostridium difficile by substituting CCA for NAAT has resulted in a lower rate of nosocomial CDI. Disclosures All authors: No reported disclosures.

scholarly journals Clinical and Economic Benefits of Fidaxomicin Compared to Vancomycin for Clostridium difficile Infection

2015 ◽  
Vol 59 (11) ◽  
pp. 7007-7010 ◽  
Author(s):  
Jason C. Gallagher ◽  
Joseph P. Reilly ◽  
Bhagyashri Navalkele ◽  
Gemma Downham ◽  
Kevin Haynes ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Treated Patient ◽  
Hospital Costs ◽  
Antibiotic Use ◽  
Economic Benefits ◽  
Drug Costs ◽  
Hospital Charges ◽  
Oral Vancomycin ◽  
Content Type ◽  
Lengths Of Stay

ABSTRACTWe studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment ofClostridium difficileinfection (CDI) in patients hospitalized during a 2-year period. This study evaluated patients who received oral vancomycin or fidaxomicin for the treatment of CDI during a 2-year period. All included patients were eligible for administration of fidaxomicin via a protocol that encouraged its use for selected patients. The primary clinical endpoint was 90-day readmission with a diagnosis of CDI. Hospital charges and insurance reimbursements for readmissions were calculated along with the cost of CDI therapy to estimate the financial impact of the choice of therapy. Recurrences were seen in 10/49 (20.4%) fidaxomicin patients and 19/46 (41.3%) vancomycin patients (P= 0.027). In a multivariate analysis that included determinations of severity of CDI, serum creatinine increases, and concomitant antibiotic use, only fidaxomicin was significantly associated with decreased recurrence (adjusted odds ratio [aOR], 0.33; 95% confidence interval [CI], 0.12 to 0.93). The total lengths of stay of readmitted patients were 183 days for vancomycin and 87 days for fidaxomicin, with costs of $454,800 and $196,200, respectively. Readmissions for CDI were reimbursed on the basis of the severity of CDI, totaling $151,136 for vancomycin and $107,176 for fidaxomicin. Fidaxomicin drug costs totaled $62,112, and vancomycin drug costs were $6,646. We calculated that the hospital lost an average of $3,286 per fidaxomicin-treated patient and $6,333 per vancomycin-treated patient, thus saving $3,047 per patient with fidaxomicin. Fidaxomicin use for CDI treatment prevented readmission and decreased hospital costs compared to use of oral vancomycin.

scholarly journals Preventable Patient Harm: a Multidisciplinary, Bundled Approach to Reducing Clostridium difficile Infections While Using a Glutamate Dehydrogenase/Toxin Immunochromatographic Assay/Nucleic Acid Amplification Test Diagnostic Algorithm

2018 ◽  
Vol 56 (9) ◽  
Author(s):  
Katherine Schultz ◽  
Emily Sickbert-Bennett ◽  
Ashley Marx ◽  
David J. Weber ◽  
Lauren M. DiBiase ◽  
...  
Keyword(s):  
Health Care ◽  
Nucleic Acid ◽  
Clostridium Difficile ◽  
Glutamate Dehydrogenase ◽  
Care Facility ◽  
Health Care Facilities ◽  
Nucleic Acid Amplification ◽  
Immunochromatographic Assay ◽  
Optimal Method ◽  
Content Type

ABSTRACT Health care facility-onset Clostridium difficile infections (HO-CDI) are an important national problem, causing increased morbidity and mortality. HO-CDI is an important metric for the Center for Medicare and Medicaid Service's (CMS) performance measures. Hospitals that fall into the worst-performing quartile in preventing hospital-acquired infections, including HO-CDI, may lose millions of dollars in reimbursement. Under pressure to reduce CDI and without a clear optimal method for C. difficile detection, health care facilities are questioning how best to use highly sensitive nucleic acid amplification tests (NAATs) to aid in the diagnosis of CDI. Our institution has used a two-step glutamate dehydrogenase (GDH)/toxin immunochromatographic assay/NAAT algorithm since 2009. In 2016, our institution set an organizational goal to reduce our CDI rates by 10% by July 2017. We achieved a statistically significant reduction of 42.7% in our HO-CDI rate by forming a multidisciplinary group to implement and monitor eight key categories of infection prevention interventions over a period of 13 months. Notably, we achieved this reduction without modifying our laboratory algorithm. Significant reductions in CDI rates can be achieved without altering sensitive laboratory testing methods.

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