Tuberculosis detection in nonhuman primates is enhanced by use of testing algorithms that include an interferon-γ release assay

OBJECTIVE To develop a testing algorithm that incorporates multiple assays to evaluate host cellular and humoral immunity and antigen detection concerning Mycobacterium tuberculosis complex (MTBC) infection in captive nonhuman primates. ANIMALS Cohorts of captive-bred and wild-caught macaques from 5 different geographic regions. PROCEDURES Macaques were tested for MTBC infection by use of a γ interferon tuberculosis (GIFT) assay, an interferon-γ release assay, and other assays. In the first 2 cohorts (n = 15 and 181), initial validation of the GIFT assay was performed by use of experimentally infected and unexposed control macaques. In the next 3 cohorts (n = 59, 42, and 11), results were obtained for opportunistically collected samples from macaques exposed during spontaneous outbreaks. RESULTS Sensitivity and specificity of the GIFT assay in the control cohorts were 100% and 97%, respectively, and were variable but enhanced by incorporating results from multiple assays in spontaneous outbreaks. CLINICAL RELEVANCE The detection and management of MTBC infection in captive nonhuman primate populations is an ongoing challenge, especially with animal imports and transfers. Despite standardized practices of initial quarantine with regular intradermal tuberculin skin testing, spontaneous outbreaks continue to be reported. Since infection encompasses a range of disease manifestations over time, a testing algorithm that incorporates multiple assays, such as the GIFT assay, to evaluate host cellular and humoral immunity in addition to agent detection is needed. Testing a combination of samples from controlled studies and spontaneous outbreaks of MTBC infection in nonhuman primates would advance the development and validation of a functional algorithm that incorporates promising tools such as the GIFT assay.

Testing as an Effective Method for Assessing the Quality of Students' Training Achievements

Electronic educational resources including testing, which simplify the process of searching and structuring educational information have been used more often in educational organizations recently. They have made learning more accessible and interesting for students of higher and vocational education institutions, especially in the context of a pandemic. The article provides a brief theoretical justification of the advantages of testing students' academic achievements. The emphasis is placed on the importance of testing as a tool for remote control of students' knowledge, the advantages and disadvantages of using tests both in the educational process of higher and secondary vocational education and in order to control the acquired knowledge are revealed. The study was carried out by the authors on the basis of a comprehensive use of theoretical and empirical methods. The leading theoretical methods were: analysis, generalization, concretization, forecasting, modeling. The work used such empirical methods as conversations, pedagogical observation, questionnaires, expert evaluation, testing, analysis of performance, generalization of pedagogical experience, methods of statistical processing of experimental data. The results presented in the article of the study of testing of students of MPSU at the initial (entrance test), current and final stage of measuring the level of educational achievements of students demonstrated an increase in the values of the effectiveness of testing at all stages of its implementation, an increase in the effectiveness of test control at the intermediate and final stages of the study. The results of the study made it possible to formulate promising directions for the development of problems of testing the quality of education of students of higher and professional education organizations: improving the forms and methods of analysis and interpretation of test results based on the invariant application of test models: improving the psychological and pedagogical orientation of the use of the testing algorithm for personalized learning trajectories in the practice of mass education, etc.

Automatic Manipulator Tracking Control Based on Moving Target Trajectory Prediction

The core issue of automatic manipulator tracking control is how to ensure the given moving target follows the expected trajectory and adapts to various uncertain factors. However, the existing moving target trajectory prediction methods rely on highly complex and accurate models, lacking the ability to generalize different automatic manipulator tracking scenarios. Therefore, this study tries to find a way to realize automatic manipulator tracking control based on moving target trajectory prediction. In particular, a moving target trajectory prediction model was established, and its parameters were optimized. Next, a tracking-training-testing algorithm was proposed for manipulator’s automatic moving target tracking, and the operating flows were detailed for training module, target detection module, and target tracking module. The proposed model and algorithm were proved effective through experiments.

A Sequential Inspection Procedure for Fault Detection in Multistage Manufacturing Processes

Fault diagnosis in multistage manufacturing processes (MMPs) is a challenging task where most of the research presented in the literature considers a predefined inspection scheme to identify the sources of variation and make the process diagnosable. In this paper, a sequential inspection procedure to detect the process fault based on a sequential testing algorithm and a minimum monitoring system is proposed. After the monitoring system detects that the process is out of statistical control, the features to be inspected (end of line or in process measurements) are defined sequentially according to the expected information gain of each potential inspection measurement. A case study is analyzed to prove the benefits of this approach with respect to a predefined inspection scheme and a randomized sequential inspection considering both the use and non-use of fault probabilities from historical maintenance data.

754. A Two-step Testing Algorithm for Hospital-onset Clostridioides difficile Infection (CDI) Reduces Prescribing of C. difficile (CD) Therapy but Its Ability to Guide Treatment Decisions Remains Unclear

Background Determining true CDI versus CD colonization through CD testing is a continuing challenge. A previously introduced decision support tool at UVA Health significantly reduced inappropriate testing without adverse outcomes. More recently, our methodology changed from nucleic acid amplification test (NAAT) alone to an initial NAAT followed by ELISA for toxin to improve specificity. The purpose of this analysis was to assess provider interpretation of test results, using targeted CD therapy as a surrogate. Methods This single-center, retrospective study evaluated all patients with a positive NAAT (Cepheid Xpert® C. difficile) on day 4 or later of hospitalization following 2-step algorithm implementation from Feb 2020 through Feb 2021. Toxin negative (TOX-) test results (C. DIFF QUIK CHEK COMPLETE®) were accompanied by a comment that discordance may represent colonization or CDI and to consider ID consult. The proportion of toxin positive (TOX+) versus TOX- patients receiving ≥ 1 dose of CD therapy served as the primary outcome with partial courses considered < 10 days. Clinical outcomes were also compared. Results Ninety patients with NAAT+ results were included, of whom 58 (64%) were TOX-. Thirty-two (100%) TOX+ (median days of therapy [IQR] = 14 [11-17]) versus 51 (88%) TOX- patients (median days of therapy [IQR] = 11 [7-14]) received CD therapy (p=0.04). Treatment decisions were guided by ID physicians for 32 (63%) TOX- patients; ID recommendations to discontinue CD therapy were followed in 2 out of 9 (22%) cases. TOX- patients received partial therapy due to patient death (n=5), presumptive colonization (n=3), and provider error (n=1). Of TOX- patients receiving partial or no treatment, there were no CDI-related adverse outcomes during the admission. CDI-related colectomy occurred in 2 (6%) and 1 (2%) TOX+ and TOX- patients, respectively. Five in-hospital deaths with CDI as a contributing factor occurred in the TOX+ group. Conclusion Adoption of a 2-step NAAT plus toxin testing algorithm for hospital-onset CDI reduced the frequency with which TOX- patients received CD therapy but the vast majority were still treated. Most providers considered a positive NAAT indicative of CDI, regardless of TOX status. Disclosures All Authors: No reported disclosures

676. Impact of Stratified Testing Algorithm Utilizing Rapid Testing and Polymerase Chain Reaction (PCR) Tests for Viral Infections

Background In 2017, the multiplex respiratory viral panel (RVP) test was the only test available for patients (pts) with respiratory symptoms in our emergency department (ED). In 2018, the more rapid influenza/respiratory syncytial virus (Flu/RSV) test was incorporated in a stratified testing algorithm (STA) – depending on clinical features and physician discretion, pts underwent either Flu/RSV or RVP. We analyzed the STA impact by comparing data between winters of 2017 and 2018. Methods In a retrospective, single-center cohort study in suburban NY, admitted pts ≥18 years diagnosed with viral infections (by either test) were included. We excluded pts diagnosed at another hospital, admitted to intensive care or observation (< 24 hours) units and pts with missing data. Data was collected through electronic medical chart review. Primary outcomes were clinical evaluation time [time between triage and test order]; laboratory-turnaround (lta) time (between order and result); ED length of stay [EDLOS] (between admit order and bed assignment). Secondary outcomes included isolation time (between result to start of isolation precautions), treatment time (between result to influenza treatment). Outcome differences were assessed using Chi-Square and Mann-Whitney rank sum tests for categorical and continuous variables, respectively. Results 734 pts were included in the study [368 in 2017; 366 in 2018]. Median age was 75 years and 55.9% were female. After implementing the STA, EDLOS was significantly lower [Table 1], with no significant differences in other parameters. Lta times were slightly higher after implementation [25 minutes (2017) v/s 29 minutes (2018)]. Table 1. Differences in clinical and laboratory turnaround times among patients admitted with viral infections in winters of 2017 and 2018 Conclusion A stratified diagnostic algorithm may have reduced EDLOS, but without significant differences in other outcomes. A higher lta time might have been due to testing constraints, heterogeneous pt populations or other confounders. Prospective studies will help assess the real-world impact of such algorithms. Disclosures Prashant Malhotra, MBBS, MD,FACP, FIDSA, Gilead Sciences (Scientific Research Study Investigator, Other Financial or Material Support, Site PI for a industry funded multi center research study)

763. Impact of Two-Step Testing Algorithm on Hospital-onset Clostridioides difficile Infections and Oral Vancomycin Prescription Practices at an Academic Medical Center

Background Clostridioides difficile infection (CDI) is one of the leading causes of hospital –onset (HO) infections. Clinically distinguishing true CDI versus colonization with C.difficile is challenging. We implemented a two-step testing algorithm to discriminate true CDI from colonization then evaluated the effect on rate of HO CDI and oral vancomycin. Methods In May 2020, a two-step testing algorithm was implemented utilizing C. difficile PCR and enzyme immunoassay (EIA) glutamate dehydrogenase (Figure 1). Rates of HO CDI and use of oral vancomycin was compared in the three quarters preceding and after this intervention (July 2019-March 2020 and July 2020-March 2021, respectively). HO CDI was defined based on National Healthcare Safety Network (NHSN) Laboratory Identified (LabID) event as last positive C.difficile test result performed on a specimen collected >3 calendar days after admission to the facility. HO CDI rates were assessed based on Standardized Infection Ratio (SIR) data and antimicrobial use was reported in days of therapy (DoT) per 1000 patient days. Figure 1. Two-Step Testing Algorithm for Diagnosing Clostridioides difficile infection Results During the pre-intervention period 30 HO CDI cases were reported compared to 9 cases in the post-intervention period (p=0.02) (Figure 2). There was a non-statistically significant reduction in CDI SIR in post-intervention period (0.133 vs. 0.305, p=0.11). Oral vancomycin use was similar in the pre- and post-intervention periods (3.89 vs. 3.84, p=0.96). Fidaxomicin use was rare (< 0.2 DoT/1000 pt days). Of 26 HO C.difficile colonized patients in post-intervention period, 14 (54%) patients received oral vancomycin treatment. Infectious diseases was consulted on 7/14 and recommended discontinuation of treatment in 3 while treatment was continued for other patients based on clinical status and immunocompromising conditions. Figure 2. Comparison of pre- and post-intervention trend in Hospital-onset CDI rate Conclusion We successfully reduced our HO CDI infections and SIR below national average after implementation of two-step testing algorithm for CDI. There was no impact on the rate of oral vancomycin use. We observed at 54% rate of treatment for patients categorized as likely colonization. Provider education and stewardship interventions are necessary to reduce inappropriate use of oral vancomycin in colonized patients. Disclosures All Authors: No reported disclosures

746. Clinical and Microbiological Characteristics of Clostridioides difficile Infection After a Change in Diagnostic Testing Algorithm

Background There is a lack of consensus on the most appropriate testing for C. difficile infection (CDI). The objective of this study was to determine the clinical and microbiological characteristics of CDI following a switch from stool PCR testing only to PCR reflexed to toxin testing. Figure 1. PCR Cycle Threshold Values Methods We reviewed the characteristics and outcomes of 50 consecutive patients who tested positive for CD by PCR (Xpert CD, Cepheid) between October 2019 and January 2020 at the Hines VA Hospital. Cases were defined by results of reflex toxin testing (Cdiff quick check complete, Alere/TechLab) after a positive PCR result. Baseline characteristics, symptoms, initial laboratory data, and treatments were compared as well as patient outcomes, including hospital readmission due to CDI at 30 days, and recurrent CDI (rCDI) at 30 and 90 days. The cycle threshold for the stool PCR result was recorded. Stools were cultured anaerobically for CD, and restriction endonuclease analysis (REA) strain typing was performed on the recovered CD isolates. Results Toxin testing was positive in 19/50 (38%) cases. Compared to stool toxin-negative cases, toxin-positive cases were older (95% vs. 71% were age ≥ 65, p = 0.06), more likely to have a history of CDI (37% vs. 23%, p = 0.34), and have ≥ 1 CDI episodes within 6 months (37% vs. 19%, p = 0.26). Treatment for CDI was more common in patients who had a positive toxin text. (95% vs 61%, p= 0.009). Among the 38 patients that received treatment, 33 received vancomycin (87%) and 8 patients (21%) had rCDI at 30 days. Of the 8 patients with rCDI, 2 were re-admitted to the hospital for CDI. The average PCR cycle threshold was lower in the toxin-positive stools compared to toxin-negative stools (24.46 and 29.96, p< 0.001; Fig. 1) The endemic REA group Y was the most common CD strain recovered (30%) and the previously epidemic and virulent REA group BI strain was recovered in 11% of the cases. Conclusion CDI cases diagnosed by positive stool PCR and positive toxin tests had more typical risk factors for CDI, a lower PCR cycle threshold and were more likely to have been treated for CDI. Outcomes were similar in this setting where infection with the virulent BI strain was uncommon. Disclosures Stuart Johnson, MD, Acurx Pharmaceuticals (Advisor or Review Panel member)Bio-K+ (Advisor or Review Panel member)Ferring Pharmaceutical (Advisor or Review Panel member)