Diagnosis Of CDI Research Articles

1089. Analytical Performance of an Ultrasensitive Immunoassay for Detection of Clostridium difficile Toxins in Stool

Background Clostridium difficile infection (CDI) is the main cause for nosocomial diarrhea. Currently available assays for the diagnosis of CDI show deficits in sensitivity, specificity, and/or turnaround time. The Singulex Clarity® C. diff toxins A/B assay, in development for the Singulex Clarity® system, was designed to provide an accurate and automated detection of C. difficile toxins A (TcdA) and B (TcdB) in stool. Here, the analytical performance of the assay is reported.MethodsLimits of detection (LoD) for TcdA and TcdB in stool and buffer was determined, and a preliminary cutoff, as compared with cell cytotoxicity neutralization assay (CCNA), was established. Analytical reactivity against 38 toxigenic and nontoxigenic C. difficile strains of eight different toxinotypes was determined. Cross-reactivity against 53 other gastrointestinal pathogens and potential interference by 11 endogenous and exogenous substances were determined. Reproducibility was tested with triplicate samples (n = 85), and stability was evaluated in samples stored at room temperature, refrigerated, and frozen conditions, and subjected to three freeze-thaw cycles.ResultsThe LoDs for TcdA and TcdB were 0.8 and 0.3 pg/mL in buffer, and 2.0 and 0.7 pg/mL in stool, respectively. Using a preliminary cutoff, the assay demonstrated 96.3% sensitivity and 96.1% specificity compared with CCNA. The Singulex Clarity® C. diff toxins A/B assay detected toxins from all tested strains and toxinotypes. No cross-reactivity or interference were detected. The repeatability was 99%, and samples for C. difficile toxin testing were stable up to 8 hours in room temperature, 1 week in 2–8°C, 6 months in −70°C, and up to three freeze–thaw cycles.ConclusionThe Singulex Clarity C. diff toxins A/B assay (in development) can detect TcdA and TcdB at very low concentrations and it has high sensitivity and specificity compared with CCNA. The assay demonstrates reactivity to common C. difficile strains, does not show cross-reactivity to common gastrointestinal pathogens, is robust against common interferents, allows for toxin detection in both fresh and frozen stool samples and up to three freeze–thaw cycles, and provides results with high reproducibility.Disclosures A. Bartolome, Singulex, Inc.: Employee, Salary. A. Almazan, Singulex, Inc.: Employee, Salary. S. Abusali, Singulex, Inc.: Employee, Salary. S. Tam, Singulex, Inc.: Employee, Salary. E. Lee, Singulex, Inc.: Employee, Salary. A. Changavi, Singulex, Inc.: Employee, Salary. W. Trinh, Singulex, Inc.: Employee, Salary. K. Chau, Singulex, Inc.: Employee, Salary. J. Estis, Singulex, Inc.: Employee, Salary. B. Noland, Singulex, Inc.: Employee, Salary. J. Bishop, Singulex, Inc.: Employee, Salary.

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.

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.

The ESCMID Study Group for Clostridium difficile: History, Role and Perspectives.

C. difficile is a major nosocomial pathogen, but is also increasingly recognised as an important diarrhoeal pathogen in the community, not always associated with antibiotics. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Clostridium difficile (ESGCD) is a group of clinicians and scientists from many European countries and further afield, who share a common interest in C. difficile. The aims of the Study Group are centred around raising the profile of CDI in humans and animals, fostering collaboration amongst centres in different European countries and providing a forum for discussing and disseminating information. One of the principal aims of the Study Group is to raise awareness of C. difficile infections in European hospitals. ESGCD has a particular interest in the development and dissemination of European guidance on prevention, diagnosis and treatment of CDI. This chapter will discuss the organisation of ESGCD within the ESCMID Study Group structure, the origins of the Study Group, the aims and objectives of the group, and will highlight some of the past and present activities of ESGCD in relation to these.

What do we know about the diagnostics, treatment and epidemiology of Clostridioides (Clostridium) difficile infection in Europe?

Clostridium difficile, recently reclassified as Clostridioides difficile is responsible for a significant part of diarrheal diseases in the hospitals and in the community. Besides the main pathogenic factors, toxin A, toxin B and the binary toxin, several other putative virulence factors have been investigated. This manuscript summarize recent findings in Europe concerning source of infection, epidemiology of CDI, the changing pattern of PCR ribotypes of C.difficile strains in different European countries, recommendations for diagnosis and treatment of CDI.

Toxin Detection by Cell Culture Neutralization Assay [CYT] and Toxin based EIA [Tox EIA] among Recurrent Episodes of CDI Diagnosed by PCR

BackgroundThe Ad Hoc C. difficile surveillance working group defines recurrent C. difficile infection as a second episode occurring >8 weeks after the index case. Due to its high sensitivity, diagnosis of recurrent CDI by PCR is extremely challenging in patients who may have persistent, PCR detectable shedding of toxigenic C. difficile (TCD) for an extended period of time after treatment of the initial CDI episode. CYT, which detects C. difficile toxin antigen, is a cumbersome test to perform but is considered as the current clinical diagnostic gold standard for CDI diagnosis. Aim: To determine the CYT and Toxin A/B EIA positivity among patients with recurrent CDI episodes detected by PCR. We further characterized the performance of diagnostic tests based on whether the recurrent episode was a relapse or reinfection.MethodsDuring a three month study period, CYT and Tox A/B EIA was performed on consecutive stool samples submitted from PCR positive recurrent episodes of CDI. For the purpose of this study, recurrence was defined as a second episode of CDI that occurred within 120 days from the most recent episode. MLST analysis was performed as previously described to characterize relapse and reinfection among the recurrent episodes (2).ResultsThirty-five recurrent episodes occurred over the study period. 21/35 [60%] were positive by CYT and 12/35 [34%] by Tox A/B EIA. Among the recurrent CDI episodes, 16 (46%) were genotypical confirmed as relapse with the original infecting strain. Majority of these relapses were positive by CYT (81%) when compared with Tox EIA (43%). Among patients with geno typically confirmed reinfection (n = 8), CYT and EIA positivity was 63 % and 50 % respectively. For the remaining 11 episodes, TCD was not retrievable in culture, CYT and EIA positivity among this group was 27 % and 9 % respectively.ConclusionForty percent of recurrent CDI episodes detected by PCR could not be confirmed by CYT. EIA missed 66 % of CYT positive recurrent CDI. The performance of CYT and EIA varied among recurrences due to relapse and reinfection. These results have significant implication for reporting of CDI HAI rates.Disclosures All authors: No reported disclosures.

Perceptions of Clostridium difficile infections among infection control professionals in Taiwan.

High Clostridium difficile colonization and infection rates among hospitalized patients had been noted in Taiwan. Nevertheless, the cognition about clinical diagnosis and management of CDI among infection control professionals in Taiwan is not clear. A 24-item survey questionnaire about the diagnosis, therapy, or infection control policies toward CDI was distributed in the annual meeting of the Infectious Disease Society of Taiwan (IDST) in October 2015 and Infectious Control Society of Taiwan (ICST) in April 2016. Totally 441 individuals responded to the survey, and 280 (63.5%) participants would routinely monitor the prevalence of CDI and 347 (78.7%) reported the formulation of infection control policies of CDI in their hospital, including contact precaution (75.7%), wearing gloves (88.9%) or dressing (80.0%) at patient care, single room isolation (49.7%), preference of soap or disinfectant-based sanitizer (83.2%) and avoidance of alcohol-based sanitizer (63.3%), and environmental disinfection with 1000ppm bleach (87.1%). For the timing of contact precaution discontinuation isolation for CDI patients, most (39.9%) participants suggested the time point of the absence of C. difficile toxin in feces. To treat mild CDI, most (61.9%) participants preferred oral metronidazole, and for severe CDI 26.1% would prescribe oral vancomycin as the drug of choice. There were substantial gaps in infection control polices and therapeutic choices for CDI between international guidelines and the perceptions of medical professionals in Taiwan. Professional education program and the setup of guideline for CDI should be considered in Taiwan.

Evaluation of Correlation between Pretest Probability for Clostridium difficile Infection and Clostridium difficile Enzyme Immunoassay Results.

The objective of this study was to evaluate the clinical characteristics and outcomes of hospitalized patients tested for Clostridium difficile and determine the correlation between pretest probability for C. difficile infection (CDI) and assay results. Patients with testing ordered for C. difficile were enrolled and assigned a high, medium, or low pretest probability of CDI based on clinical evaluation, laboratory, and imaging results. Stool was tested for C. difficile by toxin enzyme immunoassay (EIA) and toxigenic culture (TC). Chi-square analyses and the log rank test were utilized. Among the 111 patients enrolled, stool samples from nine were TC positive and four were EIA positive. Sixty-one (55%) patients had clinically significant diarrhea, 19 (17%) patients did not, and clinically significant diarrhea could not be determined for 31 (28%) patients. Seventy-two (65%) patients were assessed as having a low pretest probability of having CDI, 34 (31%) as having a medium probability, and 5 (5%) as having a high probability. None of the patients with low pretest probabilities had a positive EIA, but four were TC positive. None of the seven patients with a positive TC but a negative index EIA developed CDI within 30 days after the index test or died within 90 days after the index toxin EIA date. Pretest probability for CDI should be considered prior to ordering C. difficile testing and must be taken into account when interpreting test results. CDI is a clinical diagnosis supported by laboratory data, and the detection of toxigenic C. difficile in stool does not necessarily confirm the diagnosis of CDI.

Toxin A of the nosocomial pathogen Clostridium difficile induces primary effects in the proteome of HEp-2 cells.

This study was carried out to investigate the impact of high concentrations of Clostridium difficile toxin A (TcdA) on the proteome of human cells. It should also be examined whether a catalytically deficient mutant (TcdANXN ) has an effect on target cells. Proteome changes were investigated after treatment of HEp-2 cells with 20 nM TcdA for 8 h using a triplex SILAC labeling method and shotgun proteomics. Proteins from differently labeled and treated cells were combined for analysis using an HPLC coupled to an Orbitrap mass spectrometer. Nearly 4000 proteins were identified in each replicate and 3500 could be quantified by SILAC triplicate analysis. 51 proteins exhibited an altered abundance with 29 up-regulated and 22 down-regulated proteins. In contrast, TcdANXN had no provable impact on the protein profile of HEp-2 cells. Data analysis of regulated proteins revealed that mainly plasma membrane, cell death, cell proliferation and actin cytoskeleton proteins were affected by TcdA treatment. This proteome analysis showed novel insights of TcdA impact onepithelial cells. Comparison with long-term treatment studies reveals distinctions in affected cellular processes that will improve the understanding of TcdA functions and might help to find new tools for diagnosis and treatment of CDI.

Incidence and Predictors of 30-day Readmission among Patients Hospitalized for Clostridium difficile Infection

Introduction:Clostridium difficile infection is associated with high costs and health-care utilization. Patient characteristics and risk for hospital readmission within 30 days for CDI have not been well elucidated. In this study, we evaluated patient, hospital and clinical predictors of readmission after CDI hospitalizations. Methods: We performed a retrospective analysis using the National Readmission Database (NRD) from January 2013-December 2013 in adult patients (Age>18 years) discharged with a primary diagnosis of CDI. Index stays were identified from January to November to allow for a 30-day readmission window for all index stays. Index stays required “live” discharge status and available length of stay. Clinical variables were based on secondary diagnoses at the time of first admission and selected based on the frequency of occurrence and potential clinical value for risk stratification. Statistical analyses were performed using SAS (Version 9.4, The SAS institute, Cary, NC). Results: Overall 99,162 admissions for CDI met the criteria for index admissions, with 24,002 patients readmitted within 30 days (24%). On multivariate analysis, females were less likely to be readmitted compared to males {OR 0.91 (0.86 - 0.96)}. There were no differences in readmission rates with respect to size or ownership (government vs. private) of hospitals. Patients on Medicaid had higher rates of readmission compared to patients on Medicare {OR 1.12 (1.00 - 1.25)}, while patients with private insurance had lower rates {OR 0.68 (0.61-0.74)}. Patients who were discharged to long-term care (LTC) had a higher likelihood of readmission {OR 1.17 (1.09 -1.26)}. Higher Charlson co-morbidity index (CCI) scores (>1) were associated with readmission {OR 1.71 (1.60 - 1.83)}. Markers of increased severity of illness such as anemia {OR 1.08 (1.02 - 1.15)} and blood transfusion during admission {OR 1.33 (1.22 - 1.47)} were associated with higher odds of readmission.Figure 1Conclusion: In this exploratory study, 24% of discharges for primary CDI are readmitted within 30 days. Increasing comorbid disease, as indicated by the CCI, and increased severity of disease, as indicated by anemia and the need for blood transfusions, were associated with higher odds of readmission. Medicaid patients and those discharged to LTC also had a higher likelihood of readmission. This study identifies important potential risk factors for readmission after CDI that could be addressed in future studies and quality improvement initiatives.

Use of intravenous tigecycline in patients with severe Clostridium difficile infection: a retrospective observational cohort study

There are only a limited number of antimicrobials for treating severe Clostridium difficile infection (sCDI). Tigecycline shows significant in vitro effect against C. difficile and is approved for management of complicated intra-abdominal infections. Our aim was to analyse the efficacy of tigecycline compared with standard therapy (oral vancomycin plus intravenous metronidazole) in adults treated for sCDI. A retrospective cohort study of such patients hospitalized at our department from January 2014 to December 2015 was performed. Patients receiving tigecycline monotherapy were compared with patients treated with standard therapy alone. Diagnosis and severity of CDI were determined according to guidelines of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Primary outcome was clinical recovery, secondary outcomes were in-hospital and 90-day all-cause mortality and relapse, colectomy, and complication rates. Of the 359 patients hospitalized for sCDI, 90 (25.0%) were included, 45 in each group. Patients treated with tigecycline had significantly better outcomes of clinical cure (34/45, 75.6% vs. 24/45, 53.3%; p 0.02), less complicated disease course (13/45, 28.9% vs. 24/45, 53.3%; p 0.02), and less CDI sepsis (7/45, 15.6% vs. 18/45, 40.0%; p 0.009) compared with patients receiving standard therapy. Tigecycline usage was not associated with adverse drug reactions or need for colectomy. Rates of ileus, toxic megacolon, mortality, and relapse were similar between the two groups. Favourable outcomes suggest that tigecycline might be considered as a potential candidate for therapeutic use in cases of sCDI refractory to standard treatment.

Detection of Clostridium Difficile from Faecal Specimens of Hospitalized Patients at Theodor Bilharz Research Institute

Background: C. difficile is the leading cause of healthcare-associated diarrhea in Western countries. Objectives: To investigate the prevalence of C. difficile colonization among hospital inpatients at TBRI, its role in antibiotic-associated diarrhea; and developing an algorithm that can provide a specific, cost-effective approach to detect toxigenic C. difficile. Methodology: 87 faecal specimens obtained from 54 patients with abdominal pain and diarrhea (group A) and 33 patients with no gastrointestinal symptoms (group B) were included. All specimens subjected to screening by anaerobic culture on CCFA, GDH detection by EIA and real time PCR for genes of C. difficile; toxin production was also tested for by EIA for C. difficile toxins and real time PCR for detection of C. difficile toxins genes. Results: Using PCR, the prevalence of C. difficile was 21.8% (19 out of 87 specimens). Out of the 19 C. difficile positive specimens, 17(90%) harboured non-toxigenic organism and only 2 specimens (10%) harbour toxigenic C. difficile. By culture, sensitivity was 26.3% and specificity was 83.8%. Combining results of both culture and EIA for GDH has improved the specificity to 94.1%. Sensitivity of 100% and specificity of 87.1% were recorded when EIA for toxins was compared to PCR. Conclusions: C. difficile colonization is common among our inpatients. The high prevalence of non-toxigenic C. difficile colonization may have a protective role against infection with toxigenic strains. The use of EIA for GDH for screening for presence of C. difficile in faecal specimens followed by real-time PCR for presence of toxins genes in the samples provides a convenient, rapid and specific strategy for diagnosis of CDI.

Clostridium difficile infection after restorative proctocolectomy and ileal pouch anal anastomosis for ulcerative colitis.

Clostridium difficile infection (CDI) of the ileal pouch following restorative proctocolectomy (RPC) is becoming increasingly recognized. We aimed to understand better (i) the associated risk factors, (ii) treatment practices and (iii) the pouch diversion and failure rate in patients who developed CDI of the pouch after RPC for ulcerative colitis (UC). Patients who tested positive for C.difficile of the pouch between 2007 and 2010 were included in the analysis. Data collected included patient demographics, time from RPC to documented CDI, thetreatment of CDI and rate of excision of the pouch. Of 2785 patients recorded in the hospital CDI database, 15 had had an RPC with ileal pouch anal anastomosis. The median age was 44years and the median interval from RPC to first documented episode of CDI was 3years. Thirteen (81%) patients had had multiple episodes of pouchitis before and after CDI infection, and all were symptomatic at the time of testing for CDI. Within 30days of the diagnosis of CDI, six (40%) patients were taking immunosuppressive medication, seven (47%) were taking a proton pump inhibitor and 12 (80%) had received antibiotics. Five patients required hospitalization for CDI and four had severe infections characterized by a serum creatinine more than 1.5 times baseline (n=3) and a white cell count above 15000 (n=1). Six patients who underwent endoscopy had severe inflammation of the pouch including the presence of a pseudomembrane in one case. Ten patients were treated with metronidazole alone and five with vancomycin. Two patients had recurrent CDI of the pouch during a median follow-up period of 2.9years and one had CDI refractory to medical management. This patient required diversion of the pouch with an ileostomy for refractory CDI but no patient required excision of the pouch. All 15 patients developing CDI of the pouch were successfully treated with antibiotics and only one required surgery in the form of an ileostomy.

Ultrasensitive Detection and Quantification of Toxins for Optimized Diagnosis of Clostridium difficile Infection.

Recently developed ultrasensitive and quantitative methods for detection of Clostridium difficile toxins provide new tools for diagnosis and, potentially, for management of C. difficile infection (CDI). Compared to methods that detect toxigenic organism, ultrasensitive toxin detection may allow diagnosis of CDI with increased clinical specificity, without sacrificing clinical sensitivity; measurement of toxin levels may also provide information relevant to disease prognosis. This minireview provides an overview of these new toxin detection technologies and considers what these new tools might add to the field.

Risk Factors and Outcomes for Bloodstream Infections Secondary to Clostridium difficile Infection.

We determined the incidence, risk factors, and outcomes of bloodstream infections (BSI) subsequent to Clostridium difficile infection (CDI). We performed a retrospective study of all patients with definite diagnosis of CDI admitted from January 2014 to December 2014 in two large hospitals in Rome. Two groups of patients were analyzed: those with CDI and subsequent BSI (CDI/BSI(+)) and those with CDI and no evidence of primary BSI (CDI/BSI(-)). Data about clinical features, microbiology, treatments, and mortality were obtained. Overall, 393 cases of CDI were included in the final analysis: 72 developed a primary nosocomial BSI, while 321 had CDI without microbiological and clinical evidence of BSI. Etiologic agents of BSI were Candida species (47.3%), Enterobacteriaceae (19.4%), enterococci (13.9%), and mixed infections (19.4%). In multivariate analysis, ribotype 027 status (odds ratio [OR], 6.5), CDI recurrence (OR, 5.5), severe CDI infection (OR, 8.3), and oral vancomycin at >500 mg/day (OR, 3.1) were recognized as factors independently associated with the development of nosocomial BSI. Thirty-day mortality from CDI diagnosis was higher for patients of the CDI/BSI(+) group than for the controls (38.9 versus 13.1%; P < 0.001). Among patients of the CDI/BSI(+) group, mortality attributable to primary BSI was as high as 57%. Our findings suggest that severe CDI is complicated by the development of nosocomial BSI. Candida species and enteric bacteria appear to be the leading causative pathogens and are associated with poor outcomes.

Timing of Antibiotic Therapy in Hospitalized Patients With Clostridium difficile Infection: A Single-Center Retrospective Cohort Study

Introduction: The 2010 Infectious Diseases Society of America (IDSA) guidelines recommend that empirical treatment should be initiated as soon as the diagnosis of severe or complicated CDI is suspected. Based on these recommendations, we aimed to study whether early initiation of antibiotic therapy in hospitalized patients with CDI was associated with improved hospital based outcomes.Table 1: Baseline Characteristics: Early vs. Late Administration of AntibioticsTable 2: Outcomes for Early verus Late Administration of AntibioticsMethods: Setting: Single-center retrospective cohort study conducted at an acute care facility for the period of April 1, 2012 to December 31, 2014 Patients: Hospitalized adults with diarrhea that tested positive for CDI by polymerase chain reaction (PCR) assay, identified through the infection control committee's database. Exclusion criteria: Initiation of CDI therapy before hospitalization; lack of treatment for CDI; diagnosis and discharge from the emergency room; patients treated with intravenous metronidazole before diagnosis for non-CDI indications; and incomplete data. Definitions: Time of diagnosis was the time that the nurse received a positive diagnosis report from the microbiology lab. Treatment time was the time of antibiotic administration. In case of two antibiotics, the time of the first antibiotic was used. Median diagnosis-to-treatment time was used to separate “early” versus “late” antibiotic therapy. Severity and adherence was statified based on IDSA guidelines. Primary outcome: All cause in-hospital mortality. Secondary outcomes: Hospital length of stay (LOS), intensive care unit (ICU) LOS and CDI related surgery (ie. colectomy). Statistical Analysis: SPSS Version 19 Results: 341 cases were identified, 53 were excluded, 288 were analyzed. Diagnosis-to-treatment median time was 165 minutes. Early antibiotic therapy was associated with a non-statistically significant trend towards reduced hospital LOS (5.5 vs 7.2 days, p = 0.057), ICU LOS (1.2 vs 2.4 days, p = 0.07) and requirement for surgery (0% versus 2%, p = 0.08). There was no difference in hospital mortality between the two groups. Conclusion: Early initiation of antibiotic therapy had no effect on mortality in our cohort but was associated with a non-significant trend towards reduced hospital LOS, ICU LOS and less requirement for surgery. Our data indicate that further analysis is needed with a larger sample size to verify the importance of early administration of antibiotics on clinical outcomes in hospitalized patients with CDI.

Clinical and economic benefits of fidaxomicin compared to vancomycin for Clostridium difficile infection.

We studied the clinical and economic impact of a protocol encouraging the use of fidaxomicin as a first-line drug for treatment of Clostridium difficile infection (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.

Prevalence ofClostridium difficiletoxin in diarrhoeal stool samples of patients from a general hospital in eastern province, Saudi Arabia

Introduction<italic>Clostridium difficile</italic> is anaerobic spore-forming bacillus, produces two major toxins (Tcd A and Tcd B). Disease caused by toxigenic <italic>C.difficile (Tcd)</italic> varies from mild diarrhea to fulminant disease and death.Aims and ObjectivesThis study describes the prevalence of <italic>C.difficile</italic> toxins (CDT) in stool samples from in patients and outpatients of all age groups.Materials and MethodsA total of 146 samples were examined from 2011 to 2012 were analyzed for the presence of CDT tests, DNA amplification test, and the stool samples were cultured anaerobically on CCFA selective medium for growth-Morphology, identification and other tests. The patient's details are collected from the medical records.ResultsOut of 146 specimens, only 20 (13.7%) were positive for <italic>C.difficile</italic> toxins. Male and female were 12 (60%) and 8(40%) respectively, with the majority of them aged between 16 to 71 years. Majority of them were from out patient units (n = 5, 25%) with rest from intensive care units (n = 3, 15%), male medical ward (n =3, 15%) and surgical wards (n = 1, 5%). All the CDT positive patients had history of prior antibiotic usage before the detection of toxin. Mean duration of antibiotic usage was a 16.75 (±12.75) days, and the mean duration of diarrhea was 4.21 (±4.85) days, 16 patients had underlying medical illness, like hypertension, diabetic mellitus etc; Stool with pus cells and occult blood test was positive among that 18 patients were positive for CDT. The hospitalized patient duration was 20.96 (±16.25) days.The detection of CDT in the diagnosis of CDI requires vigilance by both clinician and microbiologist to look out for possible infected patients. Antibiotic usage is a known risk factor; thus restricted use of antibiotics may results the reduction of CDI.

Vancomycin Use for Pediatric Clostridium difficile Infection Is Increasing and Associated with Specific Patient Characteristics

In adults with Clostridium difficile infection (CDI), enteral vancomycin is considered the preferred initial regimen for severe disease; however, patterns of antimicrobial use for children with CDI are unknown. We sought to describe trends in and predictors of vancomycin use for the treatment of children with CDI admitted to tertiary-care children's hospitals in the United States. We used a database of freestanding children's hospitals to identify patients 1 to 18 years old with CDI between January 2006 and June 2011. The first hospitalization with a diagnosis of CDI for each patient was identified, and CDI-directed therapy was assessed. Generalized estimating equations were used to identify predictors of vancomycin receipt, controlling for clustering within hospitals. Vancomycin use has increased significantly (P = 0.005), with substantial variability between hospitals (0 to 16%). In multivariate analyses, vancomycin use was more common in children age 7 to 13 years old (versus children 1 to 2 years old: adjusted odds ratio [AOR] = 1.57; 95% confidence interval [CI] = 1.13 to 2.18), 14 to 18 years old (AOR = 1.40; 95% CI = 1.11 to 1.76), in an ICU (AOR = 1.37; 95% CI = 1.05 to 1.80), or with chronic gastrointestinal conditions (AOR = 2.01; 95% CI = 1.44 to 2.81). Vancomycin use was less common in black (AOR = 0.53; 95% CI = 0.39 to 0.73) and Hispanic (AOR = 0.63; 95% CI = 0.47 to 0.84) patients and in children with malignancies (AOR = 0.57; 95% CI = 0.36 to 0.89). Despite a lack of empirical evidence to suggest superiority, vancomycin use for pediatric CDI is increasing. Furthermore, there is substantial variability in vancomycin use between hospitals. Further studies are needed to explore potential racial and ethnic differences in CDI management and to investigate clinicians' rationale for using vancomycin for initial therapy in selected populations.

Easily Modified Factors Contribute to Delays in Diagnosis of Clostridium difficile Infection: a Cohort Study and Intervention

Although rapid laboratory tests are available for diagnosis of Clostridium difficile infection (CDI), delays in completion of CDI testing are common in clinical practice. We conducted a cohort study of 242 inpatients tested for CDI to determine the timing of different steps involved in diagnostic testing and to identify modifiable factors contributing to delays in diagnosis. The average time from test order to test result was 1.8 days (range, 0.2 to 10.6), with time from order to stool collection accounting for most of the delay (mean, 1.0 day; range, 0 to 10). Several modifiable factors contributed to delays, including not providing stool collection supplies to patients in a timely fashion, rejection of specimens due to incorrect labeling or leaking from the container, and holding samples in the laboratory for batch processing. Delays in testing contributed to delays in initiation of treatment for patients diagnosed with CDI and to frequent prescription of empirical CDI therapy for patients with mild to moderate symptoms whose testing was ultimately negative. An intervention that addressed several easily modified factors contributing to delays resulted in a significant decrease in the time required to complete CDI testing. These findings suggest that health care facilities may benefit from a review of their processes for CDI testing to identify and address modifiable factors that contribute to delays in diagnosis and treatment of CDI.

Performance of Clostridium difficile Toxin Enzyme Immunoassay and Nucleic Acid Amplification Tests Stratified by Patient Disease Severity

Many clinical laboratories in the United States are transitioning from toxin enzyme immunoassays (EIA) to nucleic acid amplification tests (NAATs) as the primary diagnostic test for Clostridium difficile infection (CDI). While it is known that the analytical sensitivity of the toxin EIA is poor, there are limited clinical data on the performance of these assays for patients with mild or severe CDI. Two hundred ninety-six hospital inpatients with diarrhea and clinical suspicion for CDI were tested prospectively by toxin EIA, by C. difficile NAAT, and with a reference standard toxigenic culture. Following completion of laboratory testing, retrospective chart reviews were performed to stratify patients into mild and severe disease groups based on clinical criteria using a standard point-based system. One hundred forty-three patients with CDI confirmed by toxigenic culture were evaluated in this study. Among the patients with mild CDI, 49% tested positive by toxin EIA and 98% tested positive by NAAT. Among patients with severe CDI, 58% tested positive by toxin EIA and 98% tested positive by NAAT. Increased CDI disease severity was not associated with an increased sensitivity of EIA (P = 0.31). These data demonstrate that toxin EIA performs poorly both for patients with severe CDI and for those with mild CDI and support the routine use of NAAT for the diagnosis of CDI. The presence of stool toxin measured by EIA does not correlate with disease severity.