scholarly journals The Great Masquerade: Identification of Clinically Relevant Clostridioides difficile Infections

2020 ◽  
Vol 41 (S1) ◽  
pp. s405-s405
Author(s):  
Emily Sickbert-Bennett ◽  
Lisa Stancill ◽  
Lauren DiBiase ◽  
Kevin Alby ◽  
David Jay Weber

Background: Despite clear guidance for appropriate testing of symptomatic patients for Clostridioides difficile testing (McDonald et al), the ideal testing methodology remains unresolved. Laboratories currently use different algorithms that incorporate enzyme immunoassay (EIA) testing for toxin, glutamate dehydrogenase (GDH) antigen, and polymerase chain reaction (PCR) testing in combination or as a single test. At UNC Hospitals, a large academic hospital with nearly 1,000 beds in the ninth most populous state in the United States, patients are currently tested by an EIA test for toxin and GDH antigen first, and discordant toxin/GDH results are referred for PCR testing. Previous studies have demonstrated that detection of toxin by EIA is a better predictor of C. difficile infection (CDI) complications (Polage et al). Methods: We investigated all patients who were tested for C. difficile from July 2018 to June 2019. Within each testing methodology and result, we assessed the percentage of patients with at least 3 loose stools documented within a 24-hour period, percentage with a severe episode based on white blood cell (WBC) counts >15,000 cells/mL, or percentage with a serum creatinine level >1.5 mg/dL. Fisher-type confidence intervals were calculated for each proportion. Results: Patients positive for C. difficile by the EIA method had 66.9% appropriate loose stool documentation (95% CI, 57.4%–75.5%), whereas patients with EIA-indeterminate (toxin negative, GDH positive) and positive by only PCR had 49.7% appropriate loose stool documentation (95% CI, 42.7%–56.8%). C. difficile patients that tested negative had 48.1% appropriate loose stool documentation (95% CI, 46.0–50.2%). In addition, patients positive by the EIA method had nearly double the proportion of severe disease by WBC or creatinine criteria compared to patients who were either positive by PCR or who tested negative (Table 1). Conclusions: Patients positive for C. difficile by the EIA method were statistically more likely to meet criteria for loose stool documentation. There was no statistically significant difference between patients that tested positive only by PCR or who tested negative. The percentage of patients with severe episode criteria based on WBC or creatinine was nearly doubled between those who tested positive by EIA and PCR (20% vs 10%), although this finding was not statistically significant. The percentage with severe disease (WBC or creatinine) was nearly identical among patients who were positive by PCR and who tested negative. These findings demonstrate that documentation of loose stool is a more sensitive indicator of toxin detection than either clinical parameter, reinforcing the importance of stool documentation in evaluating patients for C. difficile testing.Funding: NoneDisclosures: None

2021 ◽  
Vol 8 (9) ◽  
Author(s):  
Vishal P Shah ◽  
Wigdan H Farah ◽  
James C Hill ◽  
Leslie C Hassett ◽  
Matthew J Binnicker ◽  
...  

Abstract Cycle threshold (CT) values are correlated with the amount of viral nucleic acid in a sample and may be obtained from some qualitative real-time polymerase chain reaction tests used for diagnosis of most patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, CT values cannot be directly compared across assays, and they must be interpreted with caution as they are influenced by sample type, timing of sample collection, and assay design. Presently, the correlation between CT values and clinical outcomes is not well understood. We conducted a systematic review and meta-analysis of published studies through April 19, 2021, that reported an association between CT values and hospitalization, disease severity, and mortality in patients ≥18 years old with SARS-CoV-2. A meta-analysis of 7 studies showed no significant difference in mean CT values between hospitalized and nonhospitalized patients. Among hospitalized patients, those with CT values <25 had a high risk of more severe disease and mortality than patients with CT values >30 (odds ratio [OR], 2.31; 95% CI, 1.70 to 3.13; and OR, 2.95; 95% CI, 2.19 to 3.96; respectively). The odds of increased disease severity and mortality were less pronounced in patients with CT values of 25–30 compared with >30.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S153-S153
Author(s):  
Zahra Qamar ◽  
Lisa A Spacek ◽  
Dagan Coppock ◽  
Kaya Patel ◽  
Nathan L’Etoile ◽  
...  

Abstract Background C. difficile (CD) testing is frequently ordered inappropriately. Highly sensitive polymerase chain reaction (PCR) tests can detect CD colonization leading to misdiagnosis. Providers often overlook other causes of diarrhea, notably laxatives. To improve diagnostic stewardship, our hospital introduced an electronic medical record (EMR)-based order set (OS). Methods In a 926-bed, teaching hospital, we conducted a 3-step intervention to improve CD diagnostic stewardship. (1) A retrospective analysis of CD orders before and after OS implementation was done to assess its impact on inappropriate orders. The OS included two questions: (a) Did patient have ≥ 3 loose bowel movements in past 24 hours? and (b) No laxatives in past 24 hours? An appropriate order was defined if “yes” to both questions. It was still appropriate if “no” to either question but ≥ 2 unexplained following features: fever > 100.4 F, abdominal pain, megacolon, ileus or leukocytosis > 11,000 cells/mm3 in prior day. (2) After implementation of OS, house staff compliance with OS was surveyed via email. (3) Rationale for inappropriate orders was discussed with providers. Results Of 238 patients in retrospective analysis, 44% were ≥ 65 years and 37% had other potential causes of diarrhea. Common clinical features were leukocytosis (40%) and fever (31%). There was no significant difference in inappropriate testing: pre-OS 27/99 (27%) vs post-OS 44/139 (32%) (p=0.47). Of 43 house officers who participated in the survey, 75% indicated they over rode the OS. When asked to provide rationale of inappropriate CD testing, providers acknowledged inappropriate ordering but did not want to miss a CD diagnosis and frequently overlooked other causes of diarrhea. Conclusion Appropriate CD testing relies on providers’ appreciation of a clinical picture consistent with CD infection, confirmation of clinically significant diarrhea, and consideration of other causes of diarrhea. Providers order inappropriate tests, not due to lack of knowledge, but likely fear of missing diagnosis and overlooking other causes of diarrhea. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 31 (1) ◽  
pp. 121-133
Author(s):  
Andrea Tešija Kuna ◽  
Marijana Miler ◽  
Mario Štefanović ◽  
Ivan Šamija ◽  
Josipa Periša ◽  
...  

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests have been suggested as an additional diagnostic tool in highly suspected cases with a negative molecular test and determination of seroprevalence in population. We compared the diagnostic performance of eight commercial serological assays for IgA, IgM, and IgG antibodies to the SARS-CoV-2 virus. Materials and methods: The comparison study was performed on a total of 76 serum samples: 30 SARS-CoV-2 polymerase chain reaction (PCR)- negative and 46 SARS-CoV-2 PCR-positive patients with asymptomatic to severe disease and symptoms duration from 3-30 days. The study included: three rapid lateral flow immunochromatographic assays (LFIC), two enzyme-linked immunosorbent assays (ELISA), and three chemiluminescence immunoassays (CLIA). Results: Agreement between IgM assays were minimal to moderate (kappa 0.26 to 0.63) and for IgG moderate to excellent (kappa 0.72 to 0.92). Sensitivities improved with > 10 days of symptoms and were: 30% to 89% for IgM; 89% to 100% for IgG; 96% for IgA; 100% for IgA/IgM combination; 96% for total antibodies. Overall specificities were: 90% to 100% for IgM; 85% to 100% for IgG; 90% for IgA; 70% for IgA/IgM combination; 100% for total antibodies. Diagnostic accuracy for IgG ELISA and CIA assays were excellent (AUC ≥ 0.90), without significant difference. IgA showed significantly better diagnostic accuracy than IgM (P < 0.001). Conclusion: There is high variability between IgM assays independently of the assay format, while IgG assays showed moderate to perfect agreement. The appropriate time for testing is crucial for the proper immunity investigation.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S807-S807
Author(s):  
Jena Foreman ◽  
Neha Belter ◽  
Stephanie Thannum

Abstract Background Minimizing Clostridioides difficile infections (CDI) is an important patient safety goal due to significant cost and disease burden with CDI causing 15,000 deaths annually in the United States. Diagnosis of CDI is complicated when DNA amplification assay will return positive for both colonization and active infection of C. difficile, so testing clinically symptomatic patients with at least 3 loose stools per day is paramount to obtaining accurate reporting rates and starting proper treatment for CDI. Methods Due to economic considerations, the study was a single-center retrospective review of inpatients ≥ 18 years old who had C. difficile tests ordered from November 2017 to February 2019. Baseline characteristics collected include age, sex, white blood cell (WBC) count, fever, past C. difficile infections, recent antibiotic use, recent laxative use, and tube feeding status. Data were analyzed using descriptive statistics. The primary objective of this study was to look at the appropriateness of C. difficile tests pre and post-implementation of multidisciplinary review. Criteria for appropriateness of testing included 3 or more loose stools in addition to one additional factor including fever, elevated WBCs, immunocompromised status, or severe sepsis/septic shock. Secondary objectives include evaluating hospital-onset CDI rates and cost analysis. Results Baseline characteristics were similar between the two groups with the exception of statistically fewer patients with 3 or more liquid stools found in the post-implementation group (P = 0.0003). After implementation of a multidisciplinary review, the number of C. difficile tests ran significantly declined from 79% to 56% (P = 0.0001). The number of negative tests also were significantly reduced from 60% to 43% (P = 0.0001), with patients who had less than 3 stools per day being tested less frequently in the post-implementation group. Inappropriate test avoidance resulted in an annual savings of $1,550 in testing supplies alone, not including isolation or labor costs. There was no significant difference in hospital-onset CDI. Conclusion Implementation of a multidisciplinary review of C. difficile testing avoids clinically inappropriate tests and results in cost savings with no effect on incidence of hospital-onset CDI. Disclosures All authors: No reported disclosures.


2021 ◽  
Author(s):  
Mohamad Ammar Ayass ◽  
Jin Zhang ◽  
Kevin Zhu ◽  
Wanying Cao ◽  
Natalya Griko ◽  
...  

Background: Coronavirus disease 2019 (COVID-19) vaccines are effective at helping protect against severe disease and death from variants; however, incident of breakthrough infection in vaccinated patients has been increased. Therefore, we aimed to assess the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) new variants of concern in the communities and investigate vaccine breakthrough cases on our laboratory (Ayass Bioscience LLC) confirmed detection of COVID-19 variants in Dallas-Fort Worth (DFW), Texas. Methods: Epidemiologic study has been performed at our laboratory. We studied the viral whole-genome sequence and genotyping analysis on 166 symptomatic cases of COVID-19 which were randomly selected from nasal swab positive cases assessed from June 1st to August 30th, 2021, by reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (CT) values. COVID-19 variants were identified to be dominated by B.1.617.2 (89.2%) and followed by AY.3 (1.8%), B.1.1.7 (4.8%), a combination of B.1.526.1 and B.1.617.2 (3%), B.1.621 (0.6%), and P.2 (0.6%). Result: The CT values showed significant difference among the three age groups: <30 years, 31-60 years, and >60 years by one-way ANOVA (N1: F (2, 118) =4.96, p=0.009; N2: F (2, 118) =4.95, p=0.009). No significant difference was observed by symptom, status of immunization, or vaccine manufacturer. A two-way ANOVA was performed to examine the effect of gender and variant group (Delta and other variants) on the CT values. The analyses revealed a statistically significant interaction between the effect of gender and variant group (N1, F (1.117) = 3.906, p = 0.05; N2, F (1, 117) = 7.402, p = 0.008). Conclusion: Our study shows that Delta, the dominant variant of COVID-19, is spreading in the communities, and vaccine breakthrough cases occurred in the majority of Delta variant (91%) followed by AY.3 (5%), B.1.1.7 (2%) and 2% of the double variant of B.1.526.1 and B.1.617.2. The incidence of the breakthrough cases was not linked to a specific manufacturer. The CT value is likely to associate with age. This study also supports our laboratory's ongoing efforts to sequence the SARS-CoV-2 virus from positive patient samples to identify the new viral variants and possible vaccine breakthrough mutations in the community.


2021 ◽  
Author(s):  
Mary K Young ◽  
Jhansi L Leslie ◽  
Gregory R Madden ◽  
David M Lyerly ◽  
Robert J Carman ◽  
...  

Background. The incidence of Clostridioides difficile infection (CDI) has increased over the past two decades and is considered an urgent threat by the Centers for Disease Control. Hypervirulent strains such as ribotype 027, that possess genes for an additional toxin C. difficile binary toxin (CDT) are contributing to increased morbidity and mortality. In the mouse model, CDT activates Toll-like receptor 2 resulting in suppression of a protective type 2 innate immune response mediated by eosinophils. Methods. We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we performed 16 S rRNA gene sequencing to examine if CDT positive samples had an altered fecal microbiota. Results. We found that patients with CdtB, the pore forming component of CDT, detected in their stool were more likely to have severe disease and had higher 90-day mortality compared to CDT negative patients. CDT positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT positive and negative patients. Conclusions. Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and C. difficile Toxins A and B testing may not reveal the entire picture when diagnosing CDI and the detection of CDT-expressing strains may be valuable during patient treatment.


mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Michael G. Dieterle ◽  
Rosemary Putler ◽  
D. Alexander Perry ◽  
Anitha Menon ◽  
Lisa Abernathy-Close ◽  
...  

ABSTRACT Clostridioides difficile infection (CDI) can result in severe disease and death, with no accurate models that allow for early prediction of adverse outcomes. To address this need, we sought to develop serum-based biomarker models to predict CDI outcomes. We prospectively collected sera ≤48 h after diagnosis of CDI in two cohorts. Biomarkers were measured with a custom multiplex bead array assay. Patients were classified using IDSA severity criteria and the development of disease-related complications (DRCs), which were defined as ICU admission, colectomy, and/or death attributed to CDI. Unadjusted and adjusted models were built using logistic and elastic net modeling. The best model for severity included procalcitonin (PCT) and hepatocyte growth factor (HGF) with an area (AUC) under the receiver operating characteristic (ROC) curve of 0.74 (95% confidence interval, 0.67 to 0.81). The best model for 30-day mortality included interleukin-8 (IL-8), PCT, CXCL-5, IP-10, and IL-2Rα with an AUC of 0.89 (0.84 to 0.95). The best model for DRCs included IL-8, procalcitonin, HGF, and IL-2Rα with an AUC of 0.84 (0.73 to 0.94). To validate our models, we employed experimental infection of mice with C. difficile. Antibiotic-treated mice were challenged with C. difficile and a similar panel of serum biomarkers was measured. Applying each model to the mouse cohort of severe and nonsevere CDI revealed AUCs of 0.59 (0.44 to 0.74), 0.96 (0.90 to 1.0), and 0.89 (0.81 to 0.97). In both human and murine CDI, models based on serum biomarkers predicted adverse CDI outcomes. Our results support the use of serum-based biomarker panels to inform Clostridioides difficile infection treatment. IMPORTANCE Each year in the United States, Clostridioides difficile causes nearly 500,000 gastrointestinal infections that range from mild diarrhea to severe colitis and death. The ability to identify patients at increased risk for severe disease or mortality at the time of diagnosis of C. difficile infection (CDI) would allow clinicians to effectively allocate disease modifying therapies. In this study, we developed models consisting of only a small number of serum biomarkers that are capable of predicting both 30-day all-cause mortality and adverse outcomes of patients at time of CDI diagnosis. We were able to validate these models through experimental mouse infection. This provides evidence that the biomarkers reflect the underlying pathophysiology and that our mouse model of CDI reflects the pathogenesis of human infection. Predictive models can not only assist clinicians in identifying patients at risk for severe CDI but also be utilized for targeted enrollment in clinical trials aimed at reduction of adverse outcomes from severe CDI.


Author(s):  
Mary K Young ◽  
Jhansi L Leslie ◽  
Gregory R Madden ◽  
David M Lyerly ◽  
Robert J Carman ◽  
...  

Abstract Background The incidence of Clostridioides difficile infection (CDI) has increased over the past two decades and is considered an urgent threat by the Centers for Disease Control. Hypervirulent strains such as ribotype 027, that possess genes for the additional toxin C. difficile binary toxin (CDT), are contributing to increased morbidity and mortality. Methods We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA). Stratifying patients by CDT status, we assessed if disease severity and clinical outcomes correlated with CDT positivity. Additionally, we completed qPCR DNA extracted from patient stool to detect cdtB gene. Lastly, we performed 16 S rRNA gene sequencing to examine if CDT positive samples had an altered fecal microbiota. Results We found that patients with CdtB, the pore forming component of CDT, detected in their stool by ELISA were more likely to have severe disease with a higher 90-day mortality. CDT positive patients also had higher C. difficile bacterial burden and white blood cell counts. There was no significant difference in gut microbiome diversity between CDT positive and negative patients. Conclusions Patients with fecal samples that were positive for CDT had increased disease severity and worse clinical outcomes. Utilization of PCR and C. difficile Toxins A and B testing may not reveal the entire picture when diagnosing CDI, with the detection of CDT-expressing strains valuable in identifying patients at risk of more severe disease.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S828-S828
Author(s):  
Sarah K Hayes ◽  
Mandelin Cooper ◽  
Laurel Goldin ◽  
Sarah Fraker ◽  
Nickie Greer

Abstract Background Studies have demonstrated short courses of antibiotics, including surgical site infection (SSI) prophylaxis, can increase the risk of Clostridioides difficile infection (CDI). The purpose of this study was to evaluate the incidence of CDI associated with antibacterial perioperative prophylaxis. Methods In a retrospective analysis of affiliated hospitals from a large healthcare system, aggregate data from 156 acute care facilities across the United States was analyzed for the time period of July 2017 through July 2018. Patients were included if they were 18 years and older, admitted to an inpatient unit, and underwent a surgical procedure requiring antibiotic prophylaxis. Patients were excluded if they received antibiotics more than 24 hours prior to procedure start, received antibiotics more than 72 hours after procedure stop, or had more than one procedure with antibiotic prophylaxis within 30 days. Patients were divided into three groups based on the duration of antibiotic prophylaxis received: preoperative only (Pre-op only), pre-op plus postoperative for 24 hours or less (Short Post-op), and pre-op plus post-op for 25 to 72 hours (Long Post-op). The primary outcome was the incidence of CDI within 30 days of surgical procedure. Study design was approved by the University of Tennessee Institutional Review Board. Results The final analysis included 230,524 patients: 68,307 Pre-op Only, 123,185 Short Post-op, and 39,032 Long Post-op. Overall, 195 cases of CDI were identified during the study period, for a rate of 0.8 cases per 1000 procedures. The highest incidence occurred in the Long Post-op group (1.3 cases per 1000 procedures). A pairwise comparison demonstrated the incidence of CDI is statistically higher in the Long Post-op group compared with both the Pre-op Only (P = 0.005) and the Short Post-op (P = 0.003) groups. There was no significant difference between the Pre-op Only and the Short Post-op groups<./p> Conclusion Patients who received antibiotics for more than 24 hours post-op had a higher incidence of CDI. No statistically significant difference in CDI between pre-op only and less than 24 hours post-op was found. Disclosures All authors: No reported disclosures.


2021 ◽  
Vol 42 (2) ◽  
pp. 147-152
Author(s):  
Qing Wang ◽  
Luke Pittman ◽  
Andrew Healey ◽  
James Chang ◽  
T. Ted Song

Background: Epinephrine is the first-line therapy for patients with anaphylaxis, and intramuscular (IM) delivery is shown to be superior to subcutaneous (SC) delivery. There currently is no consensus on the ideal body position for epinephrine autoinjector (EAI) administration. Objective: We designed this study to investigate whether SC tissue depth (SCTD) is affected by body position (e.g., standing, sitting, supine), which can potentially impact delivery of EAI into the IM space. Methods: Volunteer adults (ages ≥ 18 years) from a military medical treatment facility in the United States were recruited to participate in this study. SCTD of the vastus lateralis was measured via ultrasound at standing, sitting, and supine body positions. Subjects' age, sex, and body mass index (BMI) were collected. Statistical analysis was performed to compare average SCTD between body positions, sex, and BMI. Results: An analysis of variance of 51 participants (33 men and 18 women) did not reveal statistically significant difference in SCTD among standing, sitting, and supine body positions. It did show a significantly greater SCTD in women than in men (2.72 ± 1.36 cm versus 1.10 ± 0.38 cm; p < 0.001). There was no significant association observed between BMI and SCTD in this study. Conclusion: Body position did not seem to significantly change the distance between skin and thigh muscle in adults. This would suggest that there might not be an ideal body position for EAI administration. Therefore, in case of anaphylaxis, prompt administration of epinephrine is recommended at any position.


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