1140. Impact of a Rapid Molecular Bloodstream Diagnostic Test on Optimal Antibiotic Use in Infants

Background Rapid molecular bloodstream diagnostics have been shown to decrease time-to-optimal antibiotic therapy in adult and pediatric patients. The purpose of the study was to compare the time-to-optimal antimicrobial therapy both pre-and post- implementation of rapid diagnostic testing in infants. Methods This was a single-center quasi-experimental study conducted from December 2018 to December 2020 at Children’s Hospital New Orleans. A rapid, multiplex polymerase chain reaction bloodstream diagnostic was implemented in January 2019. Antimicrobial Stewardship performed a daily review of all antimicrobials during both periods and made recommendations when necessary. The primary outcome was the difference in time-to-optimal therapy. Secondary outcomes included time-to-effective therapy, 30-day all-cause mortality rate, 30-day recurrent bacteremia rate, and time-to-microbiologic clearance. Patients were excluded if they had an unrelated concomitant infection, withdrawal of care before the result, bacteria not identified by the panel, or were over 6 months of age. Results Thirty-five and forty-three patients met inclusion criteria pre-and post-implementation. The median post-natal age was 2 months and median PRISM score was 12 in both groups. Median time-to-optimal therapy was 53.1 hours in the pre-intervention and 24.4 hours in the post-intervention group (-28.7 hours, P = 0.03). Median time-to-effective therapy was 0 and 1.4 hours, respectively (+1.4 hours, P = 0.02). There was no significant difference in 30-day all-cause mortality (3 vs. 4 patients, P = 0.62), 30-day recurrent bacteremia (0 vs. 2 patients, P = 0.2), or microbiologic clearance (37.3 vs. 26.2 hours, P = 0.09). Conclusion Implementation of a rapid, multiplex bloodstream diagnostic lead to a significant decrease in time-to-optimal antibiotic therapy in infants when compared to standard microbiological techniques. Disclosures All Authors: No reported disclosures

225. Risk Factors for Mortality in Stenotrophomonas Bacteremia: A Retrospective Study

Background Stenotrophomonas is a gram-negative organism typically associated with nosocomial infections. It is an emerging multi-drug resistant pathogen associated with significant morbidity and mortality in hospitalized patients. Optimal therapy is unknown. In this study, we evaluated the impact of treatment agent, dosing regimen, and patient characteristics on 30-day mortality for Stenotrophomonas bacteremia in our hospital system. Methods Retrospective chart review from April 2013 to September 2019 at Ronald Reagan and Santa Monica UCLA Medical Centers in Los Angeles, California. Adult patients who were hospitalized and received active therapy for Stenotrophomonas bacteremia were included in the study. Chi-square or Fischer test was used for categorical variables, Student’s t-test or Mann-Whitney U test was used for continuous variables. Results Sixty-nine patients were included in the study. The median age was 53 and 31 patients (44.9%) were female. Central line associated infections were the most common source of infection (79.7%, n = 55). Two patients (3%) had a relapse of infection. The overall 30-day mortality was 30.4% (n=21). The patients who did not survive to 30 days tended to have a higher Pitt bacteremia score, a longer length of stay, and were more likely to have used other antibiotics in the 30 days prior to culture collection. Trimethoprim-sulfamethoxazole (TMP-SMX) was the most common antibiotic used for treatment (n = 45, 65.2%). Of the patients who were treated with TMP-SMX, 19 were treated with high-dose (defined as 15 mg/kg or equivalent) and 26 had an alternative dosage after adjusting for renal function. There was no difference in 30-day mortality in the TMP-SMX high dose vs alternative dose (42.1% vs 30.8%, p = 0.53). Conclusion Stenotrophomonas bacteremia was associated with high mortality. High-dose TMP-SMX did not impact survival in our study; however, this may be due to small sample size. More research is needed to determine optimal therapy. Disclosures All Authors: No reported disclosures

49. Impact of a Rapid Genotypic Platform for Gram-negative Bloodstream Infections, Paired with an Antimicrobial Stewardship Intervention, on Time to Optimal Antimicrobial Therapy

Background Gram-negative bacteremia is associated with significant morbidity and mortality. Development of an algorithm for antimicrobial selection, using institution-specific antibiogram data and rapid diagnostics (RDT), achieves timely and appropriate antimicrobial therapy. The objective of this study is to assess the impact of a pharmacy-driven antimicrobial stewardship initiative in conjunction with ePlex® BCID on time to optimal antimicrobial therapy for patients with gram-negative bloodstream infections. Methods This retrospective, observational, single-center study included adult patients with a documented gram-negative bloodstream infection in whom the ePlex® BCID was employed. A pharmacist-driven antimicrobial stewardship intervention was initiated on December 1, 2020; pre-intervention (December 2019 – March 2020) was compared to the post-intervention (December 2020 – February 2020) period. The following organisms were included: Citrobacter spp., Escherichia coli, Klebsiella aerogenes/pneumoniae/oxytoca, Proteus spp, Enterobacter spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Polymicrobial bloodstream infections or those who had an ePlex® panel performed prior to admission were excluded. The following clinical outcomes were assessed: time to optimal antimicrobial therapy, length of stay (LOS), and inpatient-30-day mortality. Results One hundred and sixty-three met criteria for inclusion; 98 patients in the pre-intervention group and 65 patients in the post-intervention group. The mean Pitt Bacteremia Score was 1 in both groups (p=0.741). The most common organism identified by ePlex® BCID was E. coli (65.3% vs 70.8%; p=0.676). Eight E. Coli isolates were CTX-M positive; no other gene targets were detected. The most common suspected source of bacteremia was genitourinary (72.5% vs 72.3%; p=1.0). Time to optimal therapy was reduced by 29 hours [37 (31 – 55) vs. 8 (4 – 28); p=0.048). Length of stay and mortality was similar between groups. Conclusion Implementation of a rapid blood culture identification panel along with an antimicrobial stewardship intervention significantly reduced time to optimal therapy. Further studies are warranted to confirm these results. Disclosures All Authors: No reported disclosures

653. Direct Identification of Microorganisms in Positive Blood Cultures by the BioFire® FilmArray® Blood Culture Identification Panel Leads to Faster Optimal Antibiotic Therapy: A Before–After Study

Background Rapid pathogen identification from positive blood cultures may help optimize empiric antibiotic therapy quickly by reducing unnecessary broad spectrum antibiotic use and may improve patient outcomes. The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) identifies 24 pathogens directly from positive blood cultures without subculture. 3 resistance genes are included. We aimed to compare the time to optimal antibiotic therapy between BF-FA-BCIP and conventional identification. Methods We performed a single-center retrospective case-control before-after study of 386 cases (November 2018 to October 2019) with BF-FA-BCIP compared to 414 controls (August 2017 to July 2018) with conventional identification. The primary study endpoint was the time from blood sampling to implementation of optimal antimicrobial therapy. Secondary endpoints were time to effective therapy, length of hospital stay, and in-hospital and 30-day mortality. Outcomes were assessed using cause-specific Cox Proportional Hazard models and logistic regressions. Results We included 800 patients with comparable baseline characteristics. Main sources of blood stream infection (BSI) were urinary tract infection and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7% for case and control groups, respectively). Overall, 212 positive blood cultures were considered as contaminations. Identification results were available after a median of 21.9 hours by the BF-FA-BCIP and 44.3 hours by the conventional method. Patients with BF-FA-BCIP received the optimal therapy after a median of 25.5 hours (95%CI 21.0 - 31.2) as compared to 45.7 hours (95%CI 37.7 - 51.2) in the control group (Figure 1). We found no effect of the identification method on secondary outcomes. Kaplan-Meier curve representing the probability of implementing the optimal therapy at any given time according to the identification method (Standard vs. BF-FA-BCIP). Shaded ribbons represent the 95 % confidence interval (CI). The vertical dashes represent censored data. The vertical dotted lines represent the median time, i.e. the time at which 50 % of the patients obtained the optimal therapy, for the two methods. Median (95 % CI) time to optimal therapy is 45.7 (37.7 - 51.4) hours with the Standard method and 25.5 (21.0- 31.2) hours with Biofire. The tables below the curves present the numbers expecting optimal therapy according to the bacteria identification method, as well as the number of censored data in parenthesis. Panel A shows data from 0 to 900 hours. Panel B shows the data from 0 to 90 hours to better visualize how the probability to implement optimal therapy varies in the first 72 hours. Conclusion In conclusion, rapid pathogen identification by BF-FA-BCIP was associated with an almost 24h earlier initiation of the optimal antibiotic therapy in BSI. However, the overall benefit for individual patients seems to be limited. Future studies should assess the cost-effectiveness and impact on the prevention of antibiotic resistance using this diagnostic approach. Disclosures All Authors: No reported disclosures

643. Evaluation of Rapid Blood Pathogen Identification Along with Antimicrobial Stewardship at an Academic Teaching Institution

Background Bloodstream infections are a major cause of morbidity and mortality in hospitalized patients. Prompt initiation of effective antimicrobials are essential to optimize patient outcomes. New diagnostic technologies rapidly identifying bacteria, viruses, fungi, and parasites in infections of various body sites. There is a paucity of literature determining if stewardship programs run by one trained pharmacist with rapid diagnostics decreases time to optimal antimicrobial therapy. Methods This was a retrospective chart review of positive bloodstream infections identified via rapid diagnostic technologies. The EHR of admitted adult patients with positive BSI identified by BioFire FilmArray Blood Culture Identification (BCID) Panel™ or Accelerate PhenoTest Blood Culture kit™2 between January 2018 – July 2019 were evaluated and pertinent data was collected. Results Rapid diagnostic technologies identified 108 bloodstream infections due to gram positive, 56 due to gram negative, and 6 due to Candida organisms. Mean time to optimal antimicrobial therapy was significantly lower when pharmacist recommendation was accepted versus when primary care team consulted ID for recommendation or did not accept pharmacist recommendation. Mean time to optimal therapy was 14.7, 34.3, and 271.3 hours (p< 0.0001) respectively. Median total cost of visit per patient, calculated using the average wholesale price of antibiotics multiplied by the number of doses received, was significantly lower when pharmacist recommendations were accepted (&86.40, &147.95, and &239.41, respectively). Baseline characteristics Microbiological isolates Primary Outcome: Time to Optimal Therapy Conclusion The establishment of a pharmacist run antimicrobial stewardship program in conjunction with rapid diagnostic tools for identifying bacteremia led to a decrease in time to optimal antimicrobial therapy and cost savings. Introduction of similar services at community hospitals with limited ASP staffing is justified. Larger studies to further investigate whether ASP partnered with rapid diagnostics have an impact on patient-related outcomes such as mortality and length of stay is warrented. Secondary outcomes Missed cost savings Disclosures All Authors: No reported disclosures

936. Risk Factors and Clinical Outcomes for Extended-Spectrum Beta-Lactamase Producing Enterobacterales Blood Stream Infections in Patients with Hematologic Malignancies

Background Hematologic malignancy patients have high rates of antibiotic exposure, and increasing resistance is a major concern, particularly with extended-spectrum beta lactamases (ESBL) in Enterobacterales blood stream infections (BSIs). Identifying risk factors for ESBL-producing Enterobacterales (ESBL-E) BSIs may facilitate faster appropriate antibiotic use and decrease mortality. Methods This was a retrospective study of patients with hematologic malignancies and Escherichia coli or Klebsiella spp. bacteremia admitted to Carolinas Medical Center in Charlotte, NC from January 2010 through September 2020. The primary objective was to compare 30-day mortality rates for patients with ESBL-E BSIs to those with non-ESBL-E BSIs. Fisher’s exact or Mann-Whitney U tests were used for primary and secondary clinical outcomes as appropriate. Risk factors associated with 30-day mortality and ESBL production were assessed as secondary objectives using logistic regression models. Results A total of 28 patients with ESBL-E BSIs and 60 patients with non-ESBL-E BSIs were included. The 30-day mortality rate with ESBL-E BSIs was 25% compared to 15% with non-ESBL-E BSIs (P = .373). In-hospital mortality, 30-day infection recurrence, intensive care unit (ICU) admission, and length of stay after culture were not significantly different. However, time to optimal therapy was longer in the ESBL-E group (median 42.3 vs 1.9 hr; P < .001). Multivariate logistic regression analysis showed an association of 30-day mortality with ICU admission (OR 16.7; 95% CI, 3.56-78.4; P < .001) and longer time to optimal therapy (OR 1.03; 95% CI, 1.0-1.05; P = .026). Prior ESBL-positive culture was associated with ESBL-E BSI in the univariate logistic regression (OR 9.83; 95% CI, 1.05-92.56; P = .046). Additionally, prolonged neutropenia (OR 3.05; 95% CI, 1.01-9.23; P = .049) and prior intravenous antibiotic use (OR 2.96; 95% CI, 0.96-9.09; P = .059) were associated with ESBL-E BSI in the multivariate analysis. Conclusion Significantly longer time to optimal therapy was seen in ESBL-E BSIs and was associated with mortality in patients with hematologic malignancies. The identified ESBL risk factors create an opportunity to decrease delay in optimal therapy through risk stratification during initial antibiotic selection. Disclosures Ekaterina Kachur, PharmD, BCOP, Bristol Myers Squibb (Advisor or Review Panel member)Genentech (Employee)Glaxosmithkline (Advisor or Review Panel member)Kyowa Kirin (Advisor or Review Panel member)

The Optimal Control Strategy of Virus Transmission Based on Caputo-Fabrizio Order

Hepatitis B virus (HBV) is a serious threat to human health as it can cause the chronic hepatitis B, and eventually liver cancer. It also has become one of the major threats to public health in the world. In this paper, considering the rationality of using standard incidence in Caputo-Fabrizio fractional order HBV infection model, we propose a model with standard incidence. The analysis of local stability about the equilibrium and the simulation of global stability are given. We also use the real data to estimate the parameters of this model. The simulation results can fit the data well. Moreover, we propose an optimal control model and give the optimal therapy strategy, which show that optimal therapy can reduce the cost and side effects while ensuring the therapeutic effect.

Controversial and open issues of diagnosis and treatment of myocarditis (based on the discussion of Russian national recommendations)

In October 2020, the Russian Ministry of Health approved clinical guidelines for the management of patients with myocarditis. The aim of this review was to highlight controversial and open issues without unambiguous answer or those that were not described in the paper. The review highlights the objective factors that complicate the development of practical guidelines for the management of this category of patients. Comments on the definition and classification of inflammatory heart diseases are given. The approaches to the diagnosis of patients with suspected myocarditis are discussed. Particular attention is paid to the decision-making strategy in selecting optimal therapy in patients with documented myocarditis and the role of endomyocardial biopsy.