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

2020 ◽  
Vol 58 (3) ◽  
Author(s):  
Ryan Miller ◽  
J. A. Morillas ◽  
Kyle D. Brizendine ◽  
Thomas G. Fraser
Keyword(s):  
Nucleic Acid ◽  
Enzyme Immunoassay ◽  
Severe Disease ◽  
Nucleic Acid Amplification ◽  
Clinical Failure ◽  
Fulminant Colitis ◽  
Related Complication ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Complete Treatment

ABSTRACT 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.

scholarly journals Dual Reporting of Clostridioides difficile PCR and Predicted Toxin Result Based on PCR Cycle Threshold Reduces Treatment of Toxin-Negative Patients without Increases in Adverse Outcomes

2019 ◽  
Vol 57 (11) ◽  
Author(s):  
Matthew M. Hitchcock ◽  
Marisa Holubar ◽  
Catherine A. Hogan ◽  
Lucy S. Tompkins ◽  
Niaz Banaei
Keyword(s):  
Nucleic Acid ◽  
Chart Review ◽  
Patient Characteristics ◽  
Adverse Outcomes ◽  
Nucleic Acid Amplification ◽  
Content Type ◽  
Cycle Threshold ◽  
Clostridioides Difficile ◽  
All Cause Mortality ◽  
High Negative Predictive Value

ABSTRACT Nucleic acid amplification tests are commonly used to diagnose Clostridioides difficile infection (CDI). Two-step testing with a toxin enzyme immunoassay is recommended to discriminate between infection and colonization but requires additional resources. Prior studies showed that PCR cycle threshold (CT) can predict toxin positivity with high negative predictive value. Starting in October 2016, the predicted toxin result (CT-toxin) based on a validated cutoff was routinely reported at our facility. To evaluate the clinical efficacy of this reporting, all adult patients with positive GeneXpert PCR results from October 2016 through October 2017 underwent a chart review to measure the recurrence of or conversion to a CT-toxin+ result and 30-day all-cause mortality. There were 482 positive PCR tests in 430 unique patients, 282 CT-toxin+ and 200 CT-toxin−. Patient characteristics were similar at testing, though CT-toxin+ patients had higher white blood cell (WBC) counts (12.5 × 103 versus 9.3 × 103 cells/μl; P = 0.001). All cases (n = 21) of fulminant CDI had a CT-toxin+ result. Index CT-toxin+ patients were significantly more likely to have a CT-toxin+ result within 90 days than CT-toxin− patients (17.4% [n = 49] versus 8.0% [n = 16], respectively; P = 0.003). Thirty-day all-cause mortality was higher in CT-toxin− patients (11.1% versus 6.8%; P = 0.1), though no deaths in CT-toxin− patients were directly attributable to CDI. Of the 200 CT-toxin− patients, 51.5% (n = 103) were treated for CDI. The rates of conversion to a CT-toxin+ result (8.8% versus 7.2%; P = 0.8) and all-cause mortality (8.8% versus 13.4%; P = 0.3) were similar between treated and untreated CT-toxin− patients, respectively. CT-based toxin prediction may identify patients at higher risk for CDI-related complications and reduce treatment among CT-toxin− patients.

scholarly journals Increased Clinical Specificity with Ultrasensitive Detection of Clostridioides difficile Toxins: Reduction of Overdiagnosis Compared to Nucleic Acid Amplification Tests

2019 ◽  
Vol 57 (11) ◽  
Author(s):  
Johanna Sandlund ◽  
Joel Estis ◽  
Phoebe Katzenbach ◽  
Niamh Nolan ◽  
Kirstie Hinson ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Patient Outcomes ◽  
Single Molecule ◽  
Clinical Performance ◽  
Neutralization Assay ◽  
Nucleic Acid Amplification ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Health Care Associated Infections ◽  
Stool Specimens

ABSTRACT Clostridioides difficile infection (CDI) is one of the most common health care-associated infections, resulting in significant morbidity, mortality, and economic burden. Diagnosis of CDI relies on the assessment of clinical presentation and laboratory tests. We evaluated the clinical performance of ultrasensitive single-molecule counting technology for detection of C. difficile toxins A and B. Stool specimens from 298 patients with suspected CDI were tested with the nucleic acid amplification test (NAAT; BD MAX Cdiff assay or Xpert C. difficile assay) and Singulex Clarity C. diff toxins A/B assay. Specimens with discordant results were tested with the cell cytotoxicity neutralization assay (CCNA), and the results were correlated with disease severity and outcome. There were 64 NAAT-positive and 234 NAAT-negative samples. Of the 32 NAAT+/Clarity− and 4 NAAT−/Clarity+ samples, there were 26 CCNA− and 4 CCNA− samples, respectively. CDI relapse was more common in NAAT+/toxin+ patients than in NAAT+/toxin− and NAAT−/toxin− patients. The clinical specificity of Clarity and NAAT was 97.4% and 89.0%, respectively, and overdiagnosis was more than three times more common in NAAT+/toxin− than in NAAT+/toxin+ patients. The Clarity assay was superior to NAATs for the diagnosis of CDI, by reducing overdiagnosis and thereby increasing clinical specificity, and the presence of toxins was associated with negative patient outcomes.

Reductions in positive Clostridioides difficile events reportable to National Healthcare Safety Network (NHSN) with adoption of reflex enzyme immunoassay (EIA) testing in 13 Atlanta hospitals

2021 ◽  
pp. 1-4
Author(s):  
Dana Goodenough ◽  
Samantha Sefton ◽  
Elizabeth Overton ◽  
Elizabeth Smith ◽  
Colleen S. Kraft ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Enzyme Immunoassay ◽  
Infection Prevention ◽  
Nucleic Acid Amplification Test ◽  
Nucleic Acid Amplification ◽  
National Healthcare ◽  
Clostridioides Difficile ◽  
Performance Metric ◽  
National Healthcare Safety Network ◽  
Testing Practice

Abstract In total, 13 facilities changed C. difficile testing to reflexive testing by enzyme immunoassay (EIA) only after a positive nucleic acid-amplification test (NAAT); the standardized infection ratio (SIR) decreased by 46% (range, −12% to −71% per hospital). Changing testing practice greatly influenced a performance metric without changing C. difficile infection prevention practice.

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 Fluoroquinolone versus Beta-Lactam Oral Step-Down Therapy for Uncomplicated Streptococcal Bloodstream Infections

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Kellie Arensman ◽  
Maureen Shields ◽  
Maya Beganovic ◽  
Jessica L. Miller ◽  
Erik LaChance ◽  
...  
Keyword(s):  
Clinical Success ◽  
Bloodstream Infections ◽  
Pharmacokinetic Parameters ◽  
Clinical Failure ◽  
Beta Lactam ◽  
Multivariable Logistic Regression Model ◽  
Serious Adverse Events ◽  
Content Type ◽  
Clostridioides Difficile ◽  
Step Down

ABSTRACT Fluoroquinolones (FQs) are often preferred as oral step-down therapy for bloodstream infections (BSIs) due to favorable pharmacokinetic parameters; however, they are also associated with serious adverse events. The objective of this study was to compare clinical outcomes for patients who received an oral FQ versus an oral beta-lactam (BL) as step-down therapy for uncomplicated streptococcal BSIs. This multicenter, retrospective cohort study analyzed adult patients who completed therapy with an oral FQ or BL with at least one blood culture positive for a Streptococcus species from 1 January 2014 to 30 June 2019. The primary outcome was clinical success, defined as the lack of all-cause mortality, recurrent BSI with the same organism, and infection-related readmission at 90 days. A multivariable logistic regression model for predictors of clinical failure was conducted. A total of 220 patients were included, with 87 (40%) receiving an FQ and 133 (60%) receiving a BL. Step-down therapy with an oral BL was noninferior to an oral FQ (93.2% versus 92.0%; mean difference, 1.2%; 90% confidence interval [CI], −5.2 to 7.8). No differences were seen in 90-day mortality, 90-day recurrent BSI, 90-day infection-related readmission, or 90-day incidence of Clostridioides difficile-associated diarrhea. Predictors of clinical failure included oral step-down transition before day 3 (odds ratio [OR] = 5.18; 95% CI, 1.21, 22.16) and low-dose oral step-down therapy (OR = 2.74; 95% CI, 0.95, 7.90). Our results suggest that oral step-down therapy for uncomplicated streptococcal BSI with a BL is noninferior to an FQ.

scholarly journals 2356. Increased Clinical Specificity with Ultrasensitive Detection of Clostridioides difficile Toxins: Reduction of Overdiagnosis Compared with Nucleic Acid Amplification Tests

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S811-S812 ◽  
Author(s):  
Johanna Sandlund ◽  
Joel Estis ◽  
Phoebe Katzenbach ◽  
Niamh Nolan ◽  
Kirstie Hinson ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Disease Severity ◽  
Single Molecule ◽  
Clinical Performance ◽  
Neutralization Assay ◽  
Nucleic Acid Amplification ◽  
Clostridioides Difficile ◽  
Percent Agreement ◽  
Clostridioides Difficile Infection ◽  
Healthcare Associated

Abstract Background Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections, resulting in significant morbidity, mortality, and economic burden. Diagnosis of CDI relies on the assessment of clinical presentation and laboratory tests. We have evaluated the clinical performance of ultrasensitive Single Molecule Counting technology for detection of C. difficile toxins A and B. Methods Stool specimens from 298 patients with suspected CDI were tested with nucleic acid amplification test (NAAT; BD MAX™ Cdiff assay or Xpert® C. difficile assay) and Singulex Clarity® C. difficile toxins A/B assay. Specimens with discordant results were tested with cell cytotoxicity neutralization assay (CCNA), and results were correlated with disease severity and outcome. Results There were 64 NAAT-positive and 234 NAAT-negative samples. Of the 32 NAAT+/Clarity− and 4 NAAT-/Clarity+ samples, there were 26 CCNA− and 4 CCNA- samples, respectively. CDI relapse or overall death was more common in NAAT+/toxin+ patients than in NAAT+/toxin− and NAAT−/toxin− patients, and NAAT+/toxin+ patients were 3.7 times more likely to experience relapse or death (Figure 1). The clinical specificity of Clarity and NAAT was 97.4% and 89.0%, respectively, and overdiagnosis was over three times more common in NAAT+/toxin− than in NAAT+/toxin+ patients (Figure 2). Negative percent agreement between NAAT and Clarity was 98.3%, and positive percent agreement increased from 50.0% to effective 84.2% and 94.1% after CCNA testing and clinical assessment. Conclusion The Clarity assay was superior to NAATs in diagnosis of CDI, by reducing overdiagnosis and thereby increasing clinical specificity, and presence of toxins was associated with disease severity and outcome. Disclosures All authors: No reported disclosures.

scholarly journals Clostridium difficile Testing Algorithm: Is There a Difference in Patients Who Test Positive by Enzyme Immunoassay vs. Those Who Only Test Positive by Nucleic Acid Amplification Methodology?

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S394-S394
Author(s):  
Jonathan Polak ◽  
Ogheneruona Odili ◽  
Mary Ashleigh Craver ◽  
Anthony Mayen ◽  
Kyle Purrman ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Clostridium Difficile ◽  
Length Of Stay ◽  
Enzyme Immunoassay ◽  
Serum Lactate ◽  
Nucleic Acid Amplification ◽  
Categorical Variables ◽  
Grant Recipient ◽  
Stool Specimens ◽  
Chi Square Analysis

Abstract Background Testing for Clostridium difficile infection (CDI) commonly involves checking for the presence of toxins A and B by enzyme immunoassay (EIA) or nucleic acid amplification (NAA). The former is very specific, but not very sensitive. The latter is very sensitive. Beginning in 2011, our hospital incorporated an algorithm that involved testing liquid stool specimens for glutamate dehydrogenase (GDH) and toxin by EIA. For discrepant results, the stool specimen was tested for the presence of toxin by NAA. We sought to determine whether there was a difference in the baseline characteristics or outcomes between the two groups. Methods We performed a chart review of all subjects who tested positive for CDI by either method between 2011 and 2016 at Vidant Medical Center, a 909 bed, tertiary care teaching hospital. Testing was only performed on liquid stool specimens. Subjects less than 18 years of age were excluded. Repeat positive specimens were excluded. We collected demographic data including age, gender, baseline temperature, white blood cell count, and serum lactate and albumin. Length of stay and in-hospital mortality were also determined for both groups. Comparison of the two groups was done using t-test for continuous and chi-square analysis for categorical variables. Results Over the 6 year period, there were 535 positive test results. 243 specimens tested positive by EIA/GDH (EIA +); 292 specimens tested positive by GDH/NAA (NAA +). Compared with the EIA + group, the NAA + group was younger (61.8 years vs. 65.1 years, P = 0.01). There were no statistical differences in the presence of abdominal tenderness, temperature &gt;38oC, serum albumin, serum lactate, length of stay, or mortality between the two groups. The EIA + group was statistically more likely to have leukocytosis (WBC &gt;20,000 cells/mm3) at the time of the CDI testing compared with the NAA + group (P = 0.0002). Conclusion There do appear to be some clinical differences in the presentation of subjects who test positive for CDI by EIA/GDH compared with those who test positive only by GDH/NAA. These differences do not appear to affect length of stay or mortality. Disclosures P. P. Cook, Gilead: Grant Investigator, Grant recipient; Merck: Grant Investigator, Grant recipient; Pfizer: Grant Investigator and Shareholder, Grant recipient

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