Clostridium Difficile Infection Testing Research Articles

A Complex Relationship between Clostridium Difficile Infection and Graft Versus Hoste Disease: Fundeni Clinical Institute Experience

Introduction: Clostridium difficile infection (CDI) is a common complication in patients who have undergone hematopoietic stem cell transplantation (HSCT) due to prolonged hospitalization, prolonged neutropenia, use of broad-spectrum antibiotics, mucosal damage, changes in gut microbiota and compromised immunity. The incidence of CDI in patients undergoing allogeneic HSCT varies between 12 and 34% in the literature and has gradually increased in recent years in Europe North America due to the NAP1 strain. In the patient who has experienced allogeneic HSCT, diagnostic testing for CDI should include both nucleic acid amplification test (NAAT) and enzyme immunoassays (EIA) for toxins A and B, because detection of toxins A and B tests have a sensitivity of 75-80%. 5 In HSCT patients, CDI appears to be strongly associated with graft versus host disease (GVHD), gut GVHD and/or severe GVHD, but this has not been universally demonstrated. The aim: For this reason, we wanted to see whether patients who developed a CDI between day 0 and day 100 were at higher risk for gut GVHD or for severe GVHD. Results: Between January 2017 and August 2022, we performed 290 of allogeneic hematopoietic stem cell transplant procedures, in the Fundeni Clinical Institute. 50/290 developed CDI within the first 100 days after HSCT and before the diagnosis of intestinal GVHD, and 240/290 did not develop CDI. 16/50 (32%) of those with CDI developed acute GVHD, respectively 402/240 (43%) of those without CDI. From these 13/16, respectively 50/102 hade gut involvement. Of the 118 patients with acute GVHD, 13/16 in the group with CDI, respectively 30/102 in the group without CDI were assigned to severe acute GVDH (grade III and IV). Mortality due to gut GVHD in the group with CDI was 46%, respectively 14% in the group without CDI. In conclusion: CDI is not a risk factor for GVHD, but gut damage is usually associated. CDI infection is associated with severe forms of GVHD, and the implication of the digestive tract in these patients increases mortality. Also, often in the patient with digestive GVHD, CDI can coexist, making them difficult to treat.

Clostridium difficile infection and immune mediated diarrhea and colitis in patients with cancer on immune checkpoint inhibitors.

e14683 Background: Immune checkpoint inhibitors (ICIs) have altered the landscape of cancer treatment. ICIs are associated with immune mediated diarrhea and colitis (IMDC) which can be challenging to diagnose and differentiate from other etiologies of diarrhea. Clostridium difficile infection (CDI) is a common cause of diarrhea in patients with cancer and can have similar symptoms. In a similar study, CDI was found to be relatively common in ICI-treated cancer patients and especially those with IMDC requiring immunosuppressants. Our study evaluates the incidence of CDI and IMDC in patients with ICI exposure and compares clinical characteristics between the two to determine risk factors that may predispose patients to CDI or IMDC. Methods: This is a retrospective, single-center study of cancer patients on an ICI from 1/1/2011 to 4/7/2022 who were tested for Clostridium difficile with stool nucleic acid amplification tests during or after treatment with an ICI. Patients were determined to have CDI if clinically suspected and had to have a positive stool GDH Ag along with positive C. difficile toxins A & B or a positive stool C. difficile toxin B gene. Patients with positive GDH Ag in the stool but with negative toxins A&B were determined to be colonized. The diagnosis of IMDC was based on the clinical presentation and had to be made by the treating oncologist. Results: 375 patients met our study criteria and got CDI testing at any point during or after ICI exposure. 27 patients tested positive for CDI, whereas 24 were colonized. 105 patients were determined to have IMDC and 97/105 received treatment with steroids or immunosuppressants. Among patients determined to have IMDC, 6 were colonized for clostridium difficile. There were no patients with IMDC who were also positive for clostridium difficile. 71 patients were on a dual ICI regimen whereas 304 patients were on a single ICI. In patients on the dual ICI regimen, 67.6% were diagnosed with IMDC when compared to patients on a single ICI regimen where 18.8% of patients were diagnosed with IMDC (p<0.0001). The absolute lymphocyte count on the day of CDI testing was 1.185 ± 0.066 in the IMDC group when compared to 0.948 ± 0.044 in the non-IMDC group (p=0.003). The mean duration of diarrhea was longer in the IMDC group at 16.905 ± 1.211 days when compared to the CDI group at 9.852 ± 2.387 days (p= 0.0094). Smoking status, sex, history of autoimmunity, and history of prior immune related adverse events did not impact incidence of IMDC or CDI. Conclusions: IMDC was a common cause of diarrhea in patients with ICI exposure who were tested for CDI. We did not find IMDC to be a risk factor for CDI. IMDC has a longer duration of diarrhea and colitis symptoms when compared to CDI. The absolute lymphocyte count on symptom onset is higher in patients with IMDC when compared to patients with CDI and may be useful in identifying patients with IMDC earlier.

In Vitro Selection and Characterization of a DNAzyme Probe for Diverse Pathogenic Strains of Clostridium difficile.

Clostridium difficile frequently causes an infectious disease known as Clostridium difficile infection (CDI) and there are urgent needs for the development of more effective rapid diagnostic tests for CDI. Previously we have developed an RNA-cleaving fluorogenic DNAzyme (RFD) probe named RFD-CD1, which is capable of detecting a specific strain of C. difficile but is too specific to recognize other pathogenic C. difficile strains. To overcome this issue, herein we report RFD-CD2, another RFD that is not only highly specific to C. difficile but also capable of recognizing diverse pathogenic C. difficile strains. Extensive sequence and structure characterization establishes a pseudoknot structure and a significantly minimized sequence for RFD-CD2. As a fluorescence sensor, RFD-CD2 can detect C. difficile at a concentration as low as 100 CFU/mL, making this DNAzyme an attractive molecular probe for rapid diagnosis of CDI caused by diverse strains of C. difficile.

Clinical Characteristics of Patients with Clostridium Difficile Infection and Its Relationship with Fecal Occult Blood Test

Clostridium difficile infection (CDI) is an important health problem with severe morbidity and mortality. In our study, 266 adult patients admitted to the hospital between the years 2005 and 2020, and were diagnosed with CDI were included. The relationship between CDI and fecal occult blood test (FOBT) was examined, and it was aimed to determine the clinical characteristics of CDI patients and risk factors for mortality and recurrence in these patients. FOBT was found to be positive in 42.8% of our CDE patients who had occult blood in stool. Pseudomembranous enterocolitis (PME) developed in 2.2% of our patients and toxic megacolon developed in 0.8%; while 10.2% of the patients had a mortal course within 30 days and 5.2% of them had a recurrence. In our study, a significant relationship was found between mortality and advanced age, negativity of FOBT, presence of hospitalization history, and also between FOBT positivity and the presence of PME and recurrence. We believe that the data documented in this study are important because it both reveal the clinical characteristics of CDI patients and its relationship with FOBT.

Elevated White Blood Cell Count Does Not Predict Clostridium difficile Nucleic Acid Testing Results.

An elevated white blood cell count (WBC; >15 000/μL) is an established prognostic marker in patients with Clostridium difficile infection (CDI). Small observational studies have suggested that a markedly elevated WBC should prompt consideration of CDI. However, there is limited evidence correlating WBC elevation with the results of C. difficile nucleic acid amplification testing (NAAT). Retrospective review of laboratory testing, outcomes, and treatment of 16 568 consecutive patients presenting to 4 hospitals over 4 years with NAAT and WBC testing on the same day. No significant relationship between C. difficile NAAT results and concurrent WBC in the inpatient setting was observed. Although an elevated WBC did predict NAAT results in the outpatient and emergency department populations (P < .001), accuracy was poor, with receiver-operator areas under the curve of 0.59 and 0.56, respectively. An elevated WBC (>15 000/μL) in CDI was associated with a longer median hospital length of stay (15.5 vs 11.0 days; P < .01), consistent with leukocytosis as a prognostic marker in CDI. NAAT-positive inpatients with elevated WBC were more likely to be treated with metronidazole and/or vancomycin (relative ratio, 1.2; 95% confidence interval [CI], 1.1-1.3) and die in the hospital (relative ratio, 2.9; 95% CI, 2.0-4.3). Although WBC is an important prognostic indicator in patients with CDI, an isolated WBC elevation has low sensitivity and specificity as a predictor of fecal C. difficile NAAT positivity in the inpatient setting. A high or rising WBC in isolation is not a sufficient indication for CDI testing.

791. Evaluation of NSAID Exposure as a Risk Factor for Clostridium difficile infection: A Propensity-Score-Matched Case-Control Study

BackgroundExposure to certain medications, particularly antibiotics and proton pump inhibitors, has been associated with increased risk for Clostridium difficile infection (CDI). Studies have suggested an increased risk for CDI associated with exposure to certain non-steroidal anti-inflammatory drugs (NSAIDs). We conducted a retrospective case-control study to evaluate the risk for CDI associated with NSAID use.MethodsThe population included 1338 patients tested for CDI from February–December 2016 at the University of Michigan. NSAID use within 30 days of CDI testing was determined by chart review. Both scheduled and as-needed NSAID use met the definition for exposure, but aspirin use alone did not. Additional clinical data such as comorbid disease and baseline laboratory parameters were extracted through electronic query. A random forest model imputed missing data. A propensity score for NSAID use was developed via logistic regression and included gender, back pain, baseline serum creatinine, osteoarthritis, rheumatoid arthritis, serum albumin, and use of anticoagulant or antiplatelet medications. Cases were matched 1:1 with C. difficile negative controls by propensity score, with a matching caliper of 0.2 x standard deviation of the logit of the score. The final study population consisted of 1256 cases and their matched controls, however 6 cases could not be matched to controls as none had scores within the matching caliper. Conditional logistic regression was used to compare cases to controls.ResultsNSAID use was similar between the two groups on unadjusted analyses. The adjusted, multivariable model demonstrates that non-aspirin NSAID use is not a significant risk factor for CDI (P =.816), after adjustment for comorbid disease burden, age, and history of prior CDI (Table). Older age and prior CDI were independent risk factors for CDI (Table). Table Study population and modeling results ConclusionIn this retrospective case-control study, non-aspirin NSAID use was not associated with an increased risk of CDI. To our knowledge, this is the first study of NSAID use as a risk factor for CDI that accounted for bias due to treatment assignment using a propensity score. Future studies should account for frequency or chronicity of NSAID use, which may affect the results.DisclosuresKrishna Rao, MD, MS, Bio-K+ International, Inc. (Consultant)Merck and Co., Inc. (Research Grant or Support)Roche Molecular Systems, Inc. (Consultant)

Implement Electronic Decision Support to Decrease Hospital-Onset Clostridium difficile Infections at Two Community Hospitals

Background: Literature supports appropriate testing as a key factor affecting the hospital-onset (HO) Clostridium difficile infections (CDI) standardized infection ratio (SIR). In 2016, facility A was a significant outlier in HO CDI with an SIR of 2.57. In 2017, facility B had a peak SIR of 1.9. Both SIRs were considerably higher than the Centers for Medicare and Medicaid Services (CMS) national SIR of 0.997. Methods: Hospital-onset CDIF cases from both hospitals were reviewed. Current electronic decision support in the electronic health record (EHR) was evaluated for CDI laboratory orders. Literature was reviewed for best practice of appropriate specimen collection and testing. Interventions were implemented at facility A in November 2016 and facility B in June 2018. Results: In total, 67 HO CDIF cases were reviewed from both facilities (October 2015–September 2016 for facility A and April 2017–June 2018 for facility B), and 46% were due to inappropriate testing. A CDI testing order set with decision support and best practice alerts was implemented based on national best-practice guidelines (Fig. 1). Physician and nurse education were completed on appropriate testing for CDI, including symptoms and timely specimen collection. Real-time review of appropriate testing was validated by the infection prevention team, and outliers were communicated to the ordering provider. After implementation, decreases in HO-CDIF SIRs occurred at both facilities (facility A SIR, 0.36; facility B SIR, 0.56). Both facilities have been able to sustain an SIR below the current CMS national average of 0.784. Conclusions: By implementing a sophisticated order-entry process that includes electronic decision support based on best practices, clinician education, and real-time feedback to providers, patients are appropriately tested for CDI. This intervention has allowed for appropriate classification within the NHSN and has decreased the overall HO-CDIF SIR.Funding: NoneDisclosures: None

Prospective assessment of Clostridioides (formerly Clostridium) difficile colonization and acquisition in hematopoietic stem cell transplant patients.

Patients undergoing hematopoietic stem cell transplant (HSCT) possess numerous risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) and experience a high rate of diarrhea. Colonization rates of Clostridiumdifficile vary greatly among subgroup analyses with recent studies demonstrating colonization rates in the blood and marrow transplant units up to nine times that of the general population. The primary objectives of this study were to identify the rate of Cdifficile colonization and acquisition in HSCT patients admitted to the blood and marrow transplant unit. This was a prospective study that included all adult patients admitted for hematopoietic stem cell transplantation. Stool specimens were routinely collected on admission and weekly thereafter for a maximum of six samples per patient. Forty-two patients met inclusion criteria and had baseline samples available for analysis. The rate of Cdifficile colonization on admission was 24%, and an additional 9% of patients acquired the organism during admission. Twelve percent of patients developed CDI that was diagnosed clinically. Univariate analysis showed an increased risk of colonization for patients with three or more prior chemotherapy cycles. Given high colonization rates coupled with high risk of CDI in this population, providers must be judicious when testing for CDI and interpreting test results for HSCT patients.

Treatment of Helicobacter pylori Is Not Associated With Future Clostridium difficile Infection.

Helicobacter pylori (HP) infection is associated with many gastrointestinal disorders, including gastric cancer, and consensus guidelines recommend eradication after detection. There is a theoretical, yet uninvestigated, concern that HP treatment could increase the risk of Clostridium difficile infection (CDI). Using the data from a large cohort of patients with HP, we investigated whether HP eradication is associated with CDI. A retrospective cohort study within the Veterans Health Administration on 38,535 patients (median age 61.8 years; 91.8% men) with detected HP between January 1, 1994, and December 31, 2018 was conducted. Primary outcome was a positive laboratory test for CDI within 3 months of HP detection. Multivariable logistic regression evaluated the following: patient demographics, previous CDI, recent hospitalization, and whether the patient received HP eradication therapy (by antibiotic and regimen, and including proton pump therapy). Secondary analysis of those treated evaluated whether eradication of HP was associated with CDI. Among 38,535 patients, 28,818 (74.8%) were treated for HP and 284 (0.74%) developed CDI. In multivariable analysis, prominent factors included hospital discharge within 12 weeks (odds ratio [OR] 2.15; 95% confidence interval [CI]: 1.22-3.77) and 4 weeks (OR 3.46; 95% CI: 2.18-5.48), P < 0.001, and previous CDI (OR 12.5; 95% CI: 9.21-17.0, P < 0.001). Treatment of HP was not associated with future CDI. In secondary analysis of those treated, confirmation of eradication was not associated with future CDI (OR 1.49; 95% CI: 0.67-3.29). In a large study of US patients with HP, we demonstrate that neither treatment nor eradication of HP is associated with CDI. Previous C. difficile infection and recent hospital discharge, established risk factors for CDI, are strongly associated. These findings suggest that treatment should be continued to be prescribed when HP is detected (http://links.lww.com/AJG/B507).

New Approaches to Diagnostics of C.Difficile Infection

Abstract Introduction: Clostridium difficile infection (CDI) is the most common infectious cause of diarrhoea in hospitalised patients. It is a severe issue with increasing incidence in healtcare facilities and commmunities. Early and appropriate testing of CDI is very imortant. There are many different approaches that can be used in the CDI laboratory diagnostics. Recently performed studies evaluated diagnostic algorithms to optimize laboratory CDI diagnostics. The aim of the work was to implement an optimal algorithm of testing methods in CDI diagnostics. Materials and methods: The retrospective analysis of patients’ samples suspected on CDI was carried out in 2017. The data was analysed from the Laboratory Klinicka Biochemia in Zilina. The application of ESCMID re -commendation criteria for algorithm of testing, together with procedures in laboratory practice was carried out. Results: The analysis of the data showed that the applied algorithm or testing in CDI and highlighted the importance of preanalytic phase, and the evaluation of testing methods and results, together with clinical findings. Two- and three- step algorithm together with cultivation methods were applied. 87,6% of samples could be eva -luated with positive or negative results according to the 2-step algorhitm. Further samples were assessed and tested by ELISA test or PCR method. Conclusion: CDI represents a significant burden in healthcare facilities. An early diagnostics and interpretation helps to start the early treatment and helps in surveillence of the infection.

Association of Household Pets, Common Dietary Factors, and Lifestyle Factors with Clostridium difficile Infection.

Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections and is associated with significant morbidity and mortality. Since owning a cat or dog could enrich the gut microbiome, we hypothesized that it would be protective against CDI. We conducted a survey study on patients tested for CDI in order to assess whether living in the presence of a pet is associated with a decreased risk of CDI. We surveyed subjects aged 18-90 over a 14-month period using a retrospective case-control design. Subjects with CDI were matched by gender and age to patients who tested negative and had no prior history of CDI. A web-based survey was provided to subjects by mail or assisted by phone. Conditional logistic regression was used to assess for associations between CDI and the various risk factors. 205 CDI positive and 205 CDI negative subjects (response rate of 50.2%) were included. After matching for age and sex, living with a cat or dog was not associated with negative CDI testing. Exploratory multivariable modeling identified an unexpected association between positive CDI testing and high meat intake (OR 2.13, 95% CI 1.21-3.77) as well as between positive CDI testing and cat allergies (OR 1.88, 95% CI 1.02-3.46). Living with a cat or dog was not associated with negative CDI testing. Several novel risk factors for CDI have been identified including high meat intake and cat allergies.

2343. How Smart Is the Chart? Accuracy of the Medical Record in Documenting Diarrhea in Patients Tested for Clostridium difficile Infection

BackgroundInappropriate testing for Clostridium difficile infection (CDI) may result in diagnosis of CDI in asymptomatic carriers with diarrhea due to other causes such as laxatives. Current guidelines suggest that periodic chart review may be useful to assess the appropriateness of CDI testing, but it is not known how accurate the medical record is in documenting diarrhea.MethodsWe conducted a prospective cohort study of 80 patients tested for CDI to determine the accuracy of diarrhea documentation in the medical record in comparison to patient interviews and to assess the appropriateness of testing.ResultsThirty-five of 80 (44%) CDI tests were deemed inappropriate because patients either did not have clinically significant diarrhea (i.e., 3 or more unformed stools per day) or had an alternative explanation for diarrhea. Seventy-four of 80 (93%) patients stated they had diarrhea, but only 53 (66%) had clinically significant diarrhea based on symptom review. Physician and/or nursing notes documented diarrhea in 67 of 80 (84%) patients, but the number of bowel movements and the consistency of stool were documented for only 36 (45%) and 41 (51%) patients.ConclusionIn our facility, inappropriate CDI testing was common and the accuracy of the medical record in documenting diarrhea was suboptimal. Education of patients and providers may be beneficial in improving the accuracy of diarrhea documentation and the appropriateness of testing.Disclosures All authors: No reported disclosures.

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

BackgroundPrevious 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.MethodsThis 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.ResultsThe 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.ConclusionLaxative 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.

2344. Evaluation of a Best Practice Alert (BPA) to Reduce Inappropriate Testing for Clostridium difficile Infection (CDI) Within a Multi-Hospital System

BackgroundHospital-acquired CDI contribute to significant morbidity, mortality, and cost burden in hospitalized patients. Clinical practice guidelines recommend strict testing criteria when employing nucleic acid amplification testing alone as to not test asymptomatic carriers. A BPA within the electronic medical record (EMR) may assist with this screening.MethodsAt our 9-hospital system, we created a BPA to help identify patients who may not meet criteria for CDI testing. Initial BPA (January 2018) asked if patient had 3 or more stools (yes/no) and if laxatives were administered in the last 48 hours (yes/no). An expanded BPA was updated to pull medication administration records for use of laxatives in the prior 48 hours (August 2018) and notified providers of recent C. difficile testing in the past 7 days (January 2019). C. difficile orders from March 2017 (historical), March 2018 (intervention 1), and March 2019 (intervention 2) were evaluated to assess impact of these interventions.Results C. difficile testing during 30,621 (historical), 31,299 (intervention 1), and 31,960 (intervention 2) patient-days were evaluated. Rates of C. difficile orders and infections are reported in the table. Ratio of positive C. difficile specimens to tested specimens were similar between the historical arm (51 of 402; 12.7%) and both intervention 1 (42 of 271; 15.5%) and intervention 2 (45 of 316; 14.2%) arms (P = 0.3 and P = 0.5, respectively). Intervention 1 and intervention 2 arms were similar in all metrics. Statistical analysis was performed using Stata, v.14.2.ConclusionImplementation of a decision support tool to assist with C. difficile testing significantly decreased order rates in both the initial and expanded BPA intervention arms. Compared with historical rates, incidence of CDI decreased in both intervention arms though these were not statistically significant. Similarly, ratio of positive specimens to specimens tested increased in both intervention arms, though not significant, indicating a trend toward improved patient selection. To improve appropriate CDI testing, further oversight and/or education is needed to accompany implementation of an EMR decision support tool, such as BPAs. Disclosures All authors: No reported disclosures.

2831 Altering Perceptions of In-Hospital Stool Testing for Clostridioides difficile Infection Reduces Inappropriate Prescribing of Antibiotics and Length of Hospital Stay

INTRODUCTION: Clostridium Difficile Infection (CDI) occurs predominantly in the intestinal tract due to alteration of normal gut flora often due to antibiotics. Testing for CDI is common on the inpatient setting. However, we recognized that over 95% of ordered stool tests are negative for CDI which indirectly was associated with an increased length of hospital stay, the unnecessary use of antibiotics and placing patients on isolation precautions. A hospital initiative led by our team that included provider education and a special electronic order set increased the accuracy of testing for CDI at our institution. METHODS: A one-year retrospective study was done evaluating the number of symptomatic and asymptomatic patients that were tested by the toxin A/B EIA and PCR assays. Similar data was obtained from the following year after the initiation of our hospital initiative. The hospital initiative included education for all hospital prescribers as well as the creation of a special electronic order set including alerts and special restrictions implementing the Infectious Disease Society of American (IDSA) guidelines. CDI cases were reported and compared between the two groups. RESULTS: During the first study period, there were a total of 877 CDI Antigen &amp; Toxin tests ordered for inpatients. This resulted in 712 or 81% negative results for both antigen &amp; toxin. Out of 877 tests, 120 were found to have antigen positivity but negative for CD toxin (indeterminate results). These 120 patients were further analyzed by polymerase chain reaction (PCR). Only 45 out of 877 were truly positive for CDI antigen &amp; toxin (5% of total ordered tests). During the second study period, post intervention a total of 828 total CDI tests were ordered. This result showed 678 CDI tests or 82% ordered tests were negative for CDI antigen &amp; toxin. Out of 828, 101 tests were antigen positive but negative for toxin which were further analyzed by PCR. Only 49 resulted positive for CDI antigen &amp; toxin (6% of total tests ordered with positive for CDI). CONCLUSION: Our hospital initiative that included guideline-based education for ordering physicians as well as implanting an electronic order set enforcing testing criteria was effective at identifying more true positive results of CDI. We can infer that the underlying cause for the majority of symptomatic patients resulted from an etiology other than CDI. Further practitioner education with stricter measures must be enforced to reduce excessive testing.

Evaluation of a Gastrointestinal Pathogen Panel Immunoassay in Stool Testing of Patients with Suspected Clostridioides (Clostridium) difficile Infection.

Clostridioides (Clostridium) difficile infection (CDI) is the most common causative pathogen of health care-associated gastrointestinal infections; however, due to the overlap of clinical symptoms with those of other causes of acute gastroenteritis, the selection of the most appropriate laboratory test is difficult. From April to October 2018, 640 stool samples requested for CDI testing were examined using the mariPOC CDI and Gastro test (ArcDia), which allows the detection of C. difficile glutamate dehydrogenase (GDH) and toxin A/B, norovirus genogroups GI and GII.4, rotavirus, adenovirus, and Campylobacter spp. In parallel, the C. Diff Quik Chek Complete test (Alere) was used as a routine diagnostic assay, and C. difficile toxigenic culture was used as a reference method. The sensitivity of the mariPOC CDI and Gastro test was comparable to that of C. Diff Quik Chek Complete for the detection of GDH (96.40% [95% confidence interval {CI}, 91.81% to 98.82%] versus 95.68% [95% CI, 90.84 to 98.40%]; P = 1.00) and was higher for the detection of toxin A/B (66.67% [95% CI, 57.36 to 75.11%] versus 55.56% [95% CI, 46.08 to 64.74%]; P = 0.00). The specificity of the mariPOC CDI and Gastro test was lower than that of C. Diff Quik Chek Complete for GDH detection (95.21% [95% CI, 92.96% to 96.91%] versus 97.60% [95% CI, 95.85% to 98.76%]; P = 0.04) and comparable to that of C. Diff Quik Chek Complete for toxin A/B detection (99.24 [95% CI, 98.05% to 99.79%] versus 99.81% [95% CI, 98.94% to 100.0%]; P = 0.37). In 29 cases (4.53%), other causative agents of diarrhea were detected (Campylobacter spp. [n = 17], rotavirus [n = 7], and norovirus genogroup GII.4 [n = 5]).

Clostridium difficile infection in fever patients with gynecological malignancies.

Although Clostridium difficile infection (CDI) often results in severe manifestations due to toxin-producing clostridium, the correlation between CDI and having a fever in gynecological malignancies is not completely understood. The incidence, and clinical features, and clinical management of CDI in patients with gynecological malignancies who have fevers were investigated, and the clinical managements of this complication are discussed. We retrospectively reviewed 485 patients newly diagnosed with invasive gynecological cancers who underwent anticancer treatment between July 2012 and December 2016. The diagnosis of CDI was performed using enzyme immunoassays for Cdifficile glutamate dehydrogenase and toxin A/B enzyme immunoassay. The cumulative risk of CDI was 9.5% (six of 63) in overall fever patients and 6.3% (six of 95) in patients with fever episodes. Two CDI patients (33.3%) did not show diarrheal symptoms, with the fever of unknown origin criteria prompting their CDI testing and diagnosis. CDI patients were treated using vancomycin or metronidazole without suffering from fatal clinical course. Overall, eight patients with gynecological malignancies were diagnosed with CDI, including two patients with fever lower than 38.5°C. The cumulative risk of CDI was 0.48% (eight of 1652) for all admitted patients and 1.6% (eight of 485) in those with gynecological malignancies. Of all the patients with confirmed CDI, only one had a history of administration of antibiotics prior to onset of CDI symptoms. CDI does not always present with typical manifestations in malignancy patients. Investigation of CDI, regardless of gastrointestinal symptoms or history of antibiotic use, is warranted in cases of fever of unknown origin in gynecological malignancy.

Mandatory Pre-Authorization or “Hard Stop Order” to Decrease Inappropriate Testing for Clostridium difficile Infection. A Testing Stewardship at 2 Hospitals.

BACKGROUND Despite implementation of the Clostridium difficile Infection (CDI) algorithm in 2016, inappropriate testing remains an issue. To further reduce this problem, Mandatory Pre-Authorization (MPrA) or Hard Stop Order (HSO) was implemented in March 2017. MPrA/HSO requires the ordering physician to apply the criteria set in the algorithm and obtain approval from an Infectious Disease (ID) physician. The test is stopped if the criteria are not met and without approval. The objective of this review is to examine the effectiveness of the MPrA/HSO in our hospitals. METHODS An order set was built in the electronic medical record (EMR) identifying the ordering physician and ID attending approving the test. Educational sessions, posters and pocket size algorithm were provided. Orders without ID approval were referred back to the ordering physician or escalated to the Chief of Service or to the Director of Infection Prevention. Exclusion for the MPrA/HSO were Emergency Room patients suspected with CDI. National Healthcare Safety Network (NHSN) data from February 2016 to March 2018 were retrospectively analyzed. RESULTS Comparison of Pre and Post implementation data showed a decline of 68% in CDI testing for Hospital A and 61% for Hospital B. The Hospital-Onset CDI dipped to 74% in Hospital A and 61% in Hospital B and inappropriate testing decreased by 75% and 100% respectively. >97% met testing criteria and ID approval. Pre and Post MPrA/HSO Standard Infection Ratio (SIR) were statistically significant. CONCLUSIONS Testing stewardship accomplished a reduction of CDI testing without a corresponding increase in CDI, and without evidence of missed cases. Our goal of reducing inappropriate testing is achieved, thereby improving patient outcome as unnecessary isolation and exposure to antibiotics are avoided. Administrative support, interdisciplinary teamwork and integration of the MPrA/HSO in the EMR are essential in the success of this initiative.

Implementation of an Algorithm Decision Tree Increases Compliance with Clostridium difficile Testing

BACKGROUND Clostridium difficile infection (CDI) is life-threatening disease that causes diarrhea. Risk factors include hospitalized patients who are receiving antibiotics. Laboratory tests commonly used to diagnose CDI include molecular tests, which is highly sensitive and specific, and antigen detection, which uses a two-step testing algorithm. While molecular tests do provide rapid identification, they do not differentiate between colonization and infection, and as a result patients may be unnecessarily treated for CDI. The objective of this initiative was to simplify the decision-making process for the front-line staff, by creating an algorithm to aid in proper CDI testing. METHODS A CDI algorithm was implemented in January 2017 and it consisted of a flowchart with check boxes. If all boxes were checked, then patient met criteria for testing. All specimens sent to the laboratory required the algorithm filled out appropriately with two signatures. If the algorithm was not submitted with the specimen, the laboratory called the unit to request a completed algorithm. The study compared the total number of tests performed and hospital-onset (HO) cases (Pre: January-December 2016, Post: January-December 2017). RESULTS During the pre-intervention period, a total of 1873 tests were performed, and of those, 70 were HO cases. During the post-intervention period, a total of 1358 tests were performed, and of those, 39 were HO cases. Total number of tests performed was reduced by 27% and overall HO cases was reduced by 44% as a result of the intervention. CONCLUSIONS This initiative demonstrates that creating a CDI algorithm, increases compliance with CDI testing. The results were validated with a decrease in the overall number of tests performed and in HO cases. Use of the CDI algorithm decreases unnecessary testing, decreases unnecessary treatment for colonized patients, and increases patient safety.

Laboratory-developed test for detection of acute Clostridium difficile infections with the capacity for quantitative sample normalization

We describe a laboratory-developed test intended for the detection of acute Clostridium difficile infections (CDI) with the capacity for quantitative sample normalization. The test is based on the detection of the tcdB gene. However, this biomarker is also present among people without symptoms, implying that individuals with diarrhea, not caused by C. difficile may nonetheless test positive. Therefore, clinical diagnosis based on this format of testing can be challenging. In order to improve diagnostic assays capability, tcdB-based quantification methods were suggested as a potential solution, however they did not increase clinical specificity. We report methodology for a dual biomarker monitoring (total bacterial load and tcdB assay), allowing for the calculation of the relative presence of tcdB in the total bacterial population in the tested samples. We believe that this approach is clinically relevant to current assays and can improve CDI testing algorithms.