Antibiotic De-escalation Research Articles

123. Utilization of the BioFire® FilmArray® Pneumonia Panel in Critically Ill Patients with Influenza Pneumonia

BackgroundSevere influenza pneumonia is associated with poor clinical outcomes and may be complicated by bacterial co-infections. Traditional culture techniques may fail to identify organisms, especially if antibiotics were administered prior to culture collection. In critically ill patients, negative cultures may lead to prolonged use of empiric, broad-spectrum antibiotics.MethodsThis is a single-center descriptive study on the use of the BioFire® FilmArray® Pneumonia (PNA) panel in critically ill patients with influenza. All intubated patients diagnosed with influenza pneumonia admitted to an ICU between December 1, 2019 and March 31, 2020 were included for analysis. The purpose of this study was to compare the results from rapid diagnostic testing with traditional culture results, and to describe the impact on time to results and the time to de-escalation of antibiotics.ResultsA total of 21 patients with 22 PNA panels were included. The mean age was 64 years, and 43% were female. Diabetes and COPD were present in 29% and 33%, respectively. A majority of patients (91%) had influenza A. Bacterial co-infection was found in 82% of cases, with all having bacteria identified on the PNA panel. Polymicrobial results from the PNA panel occurred 32% of the time. The most frequently identified bacterial pathogens by PNA panel were S. pneumoniae (41%), MSSA (27%), H. influenzae (14%), and P. aeruginosa (9%). Respiratory cultures had no growth 50% of the time, with MSSA most commonly identified at 23%. P. aeruginosa and MRSA were the only organisms that were detected by both PNA panel and respiratory culture with 100% agreement. PNA panel results were available 5.1 (2.7–11.3) hours after respiratory culture collection, compared to 45.8 (31.5–55.6) hours for culture results. De-escalation of empiric antibiotics occurred 13.2 (1.7–24.0) hours after PNA panel results in the 18 evaluable patients.Table 1: Pathogens Identified by BioFire Pneumonia Panel and Respiratory Culture ConclusionThe PNA panel identified a high rate of bacterial pathogens in this cohort of critically ill patients with influenza. It also provided actionable results much quicker than traditional respiratory cultures. Further study is needed to evaluate the significance of positive molecular tests when cultures are negative.Disclosures All Authors: No reported disclosures

53. Effect of rapid identification of bloodstream isolates on antibiotic management using a pharmacist-based treatment algorithm

BackgroundThe use of rapid molecular diagnostic testing to identify microorganisms and resistance markers has great potential to optimize medical care and assist with antimicrobial stewardship. We implemented the Verigene bloodstream infection testing panel along with a pharmacy notification system to clinicians and assessed efficacy of the system.MethodsIn November 2019, we implemented the Verigene gram positive and negative panels for patients with positive blood cultures. Our antimicrobial stewardship committee developed a recommended treatment algorithm for pharmacists to use when notified of Verigene results. The first positive bottle per patient and per admission was tested. Subsequent positive bottles were not tested on the Verigene unless a different morphology was noted on the gram stain. A gram stain was performed on all positive cultures and this result was called to the patient’s nurse (if inpatient) and the covering physician was notified of the result. After the Verigene result was available, an assigned pharmacist was notified of these results (organism identification and resistance markers if identified). Pharmacists notified covering physicians of the test results and the recommended antibiotic management. Pharmacists documented the frequency that the test result changed the antibiotic management, including escalation, de-escalation or no change in therapy. The data from the first six months was summarized.ResultsFrom 11/19/19-5/18/20, a total of 575 test results were called into the pharmacist (average 3.2/day). Among these, 165 (28.7%) were considered likely contaminants, 106 had no change in therapy and 59 had antibiotic de-escalation. Among the remaining 410 patients, 156 had de-escalation, 53 had escalation, 30 were not on any antibiotics and appropriate antibiotics were started. Overall, antibiotic management changed in 298/575 (51.8%) of isolates run by Verigene in our institution including 215 (37.4%) de-escalations. The most frequent antibiotics that were stopped included vancomycin (142) and cefepime (53).ConclusionOur pharmacist-based algorithm for notification and treatment recommendation based on Verigene results was highly successful in optimizing antibiotic management and improving antimicrobial stewardship in our institution.Disclosures All Authors: No reported disclosures

1476. Impact of an Educational Campaign on Rates of Sputum Culture Acquisition as an Opportunity for Antibiotic De-escalation

BackgroundThe 2019 community-acquired pneumonia (CAP) guidelines recommend obtaining a sputum culture in patients who are empirically treated for methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa to assist clinicians in optimizing antimicrobial therapy. A previous study at our institution found respiratory cultures were rarely obtained in patients with CAP. As a result of these findings, an educational campaign was implemented to promote the use of an induced sputum protocol.MethodsThis was a multicenter, retrospective cohort study that included patients who were ≥18 years of age, had a diagnosis of CAP, and received ≥48 hours of anti-pseudomonal antibiotics. Patients were excluded if mechanically ventilated within 48 hours of admission or diagnosed with hospital-acquired or ventilator-associated pneumonia. Patients were grouped into pre- and post-intervention time periods. The intervention involved education on obtaining respiratory cultures including technique on induced sputums and updates to CAP order sets. The primary outcome was the rate of sputum culture acquisition. Secondary outcomes included duration of anti-pseudomonal and anti-MRSA therapy, in-hospital mortality, and length of stay.ResultsA total of 143 patients met inclusion criteria, 72 in the pre-implementation group and 71 in the post-implementation group. Baseline characteristics were similar between the two groups. More patients in the post-implementation group had a sputum culture obtained but the difference was not statistically significant (38.9% vs 53.5%; p=0.08). Anti-pseudomonal therapy was continued for an average of 5.6 days pre-implementation and 5.2 days post-implementation (p=0.499). There was also not a significant difference in anti-MRSA duration between the two groups (3.4 days vs 3.2 days; p=0.606). In-hospital mortality and length of stay were similar between the two groups.ConclusionAn educational campaign focusing on the acquisition of induced sputums led to an increase in rates of sputum cultures collected. However, this did not correlate with a decrease in duration of anti-MRSA or anti-pseudomonal therapy. Further interventions should be made to optimize de-escalation of broad spectrum antibiotics based on sputum culture results.Disclosures All Authors: No reported disclosures

574. De-escalation of Broad Spectrum Antibiotics during Cytokine Release Syndrome with Haploidentical Hematopoietic Stem Cell Transplantation

BackgroundFever is a common component of cytokine release syndrome (CRS) occurring in 90% of patients undergoing haploidentical hematopoietic stem cell transplantation (Haplo-HSCT). Fevers typically occur between the stem cell infusion (Day 0) and initiation of post-transplant cyclophosphamide and are often confused with febrile neutropenia (FN). Due to longer time to engraftment in Haplo-HSCT, CRS/FN exposes patients to prolonged courses of empiric broad spectrum antibiotic (BSA) therapy increasing the risk for multi-drug resistant organisms. Recently, at Yale New Haven Health, our practice has changed to now recommend antibiotic de-escalation to prophylaxis after 7 days of BSA if no infection is identified. The objective of this study was to assess the incidence of breakthrough infections with the de-escalation of BSA in CRS/FN. Secondary endpoints include rate of FN, rate of de-escalation, rate of recurrent fevers, duration of BSA, and positive blood culture data.MethodsThe patient population included those undergoing Haplo-HSCT between July 2016 and February 2020 and who developed CRS/FN between Day 0 and Day +5. Patients were excluded if they had prolonged hospitalization due to non-infectious complications or engraftment failure. Bacteremia was defined using NHSN definitions.ResultsOf the 53 Haplo-HSCTs assessed, 43 experienced CRS/FN. Thirty-five Haplo-HSCT (81%) with CRS/FN had negative cultures and 23 (66%) of these were de-escalated back to antibacterial prophylaxis. The median duration of BSA in the de-escalated group was 7 days (range 5–13) compared to 16.5 days range (13–21) in the non-de-escalated group (p< 0.001). Among those de-escalated, 7 (30%) had recurrent fever occurring at a median of 4 days (range 2–14) and were placed back on BSA. Two Haplo-HSCT (9%) that had fever after de-escalation developed a breakthrough bacteremia. No Haplo-HSCT after de-escalation had fever or re-admission for bacteremia 30 days after engraftment. Four Haplo-HSCT (9%) with CRS/FN had positive blood cultures; however, three (7%) were still able to be de-escalated from BSA to narrower agents based on susceptibilities.ConclusionDe-escalation of BSA in FN/CRS in Haplo-HSCT patients reduced unnecessary, prolonged antibiotic exposure with a low incidence of breakthrough infections.Disclosures All Authors: No reported disclosures

197. Bridging the Divide Between Antimicrobial Stewardship and Surgical Services: Successful Use of Handshake Stewardship with Hepato-Pancreato-Biliary Surgical Services in Adult Patients at a Large Academic Medical Center

BackgroundHandshake stewardship has displayed promise in engaging providers in the pediatric population but literature in adults are lacking. Face-to-face interactions are proposed to improve antibiotic stewardship (ASP) efforts in challenging services that have low ASP acceptance and commonly utilize broad-spectrum antibiotics (BSA) such as Hepato-Pancreato-Biliary surgical services (HPBSS).MethodsHandshake stewardship was initiated by the Antimicrobial Support Network (ASN) with the HPBSS at the Carolinas Medical Center in January 2019. In-person rounding was completed. Treatment algorithms were created to assist in standardizing antibiotic selection and de-escalation for common HPB infections. To evaluate the impact of handshake stewardship, we assessed antimicrobial utilization of BSA by measuring days of therapy (DOT) per 1000 patient days (PD), comparing the pre- (Jan – Dec 2018) and post-intervention period (Jan – Dec 2019). ASN intervention acceptance rates and rates of hospital-acquired (HA) carbapenem-resistant Enterobacterales (CRE) infections/colonization and C. difficile infections (CDI) were also collected.ResultsAfter implementation of handshake stewardship, antipseudomonal use decreased significantly by 32.5 DOT/1000 PD as compared to the pre-intervention period (174.4 vs 141.9 DOT/1000 PD, p = 0.04). A numeric decrease in carbapenem use was also observed (21.7 vs 57.5 DOT/1000 PD, p = 0.275). ASN intervention acceptance rates significantly increased by 31% (p < 0.01). HA-CRE infections, CRE colonization and CDI decreased by 87.7%, 66% and 38.8%, respectively (p = ns).Figure 1: HPB Antibiotic Utilization FIgure 2: ASN Intervention Rates with HPB Table 1. Rates of CRE and C. difficile Infections ConclusionUse of handshake stewardship assisted in reducing BSA use, improving provider acceptance of ASN interventions and decreasing HA-infection rates. Based on these findings, handshake stewardship may be useful in services that display challenges in implementing ASP due to their complex patient populations, such as HPBSS.Disclosures All Authors: No reported disclosures

240. Reduction of antibiotic use in children admitted with viral respiratory tract infections

BackgroundViral respiratory tract infections (VRTI) accounts for a significant proportion of hospitalized children and contributes to a substantial use of health care resources and costs. American Academy of Pediatrics (AAP) recommends against using antibiotics in uncomplicated viral respiratory infections in children. Overuse of antibiotics ranges between 29–80%. The goal of an Antibiotic stewardship programs (ASP) is to decrease antibiotic misuse, lower costs, and prevent emergence of antibiotic resistance in the community.Proportion of children with Viral respiratory tract infections on antibiotics MethodsOur smart aim was to reduce antibiotic use by 25% in admitted children with VRTI between October 2019-March 2020. Our outcome measure was to reduce inappropriate antibiotic use during the 2019–20 season by 25%. Process measures included percentage of antibiotic used in viral RTI, antibiotic days of therapy and appropriate audit-feedback from the ASP team to facilitate discontinuation or de-escalation of antibiotics based on culture data. Our balance measure included readmission rates in patients in whom antibiotics were discontinued or de-escalated. Several PDSA cycles implemented with predominant emphasis on communication between ASP team and primary providers.ResultsNo differences were noted in patient demographics including sex, age, ethnicity between the viral season in 2018–19 and 2019–2020. In our previous study in 2018–2019 RSV season, there was 40.7% antibiotic use in patients admitted with RSV bronchiolitis. In 2019–2020 season we included all patients admitted with viral RTI. Of the 213 patients evaluated between October 2019 through Dec 2020, 40% of the patients received antibiotics. 100% of the antibiotics were justified, based on independent review of antibiotic data by the team. Most common cause of antibiotics were community acquired pneumonia, rule out sepsis and otitis media. Antibiotic discontinuation and de-escalation were achieved in over 90% of the justified antibiotics.ConclusionThough antibiotic usage was still at 40% at our institution, 100% of antibiotic use was deemed appropriate and significant proportion were discontinued or deescalated by the ASP team.The ASP team played a crucial role in communicating with the primary providers to advocate for appropriate antibiotic use in the children.Disclosures All Authors: No reported disclosures

272. Clinical Outcomes with Continuation of Combination Antibiotic Therapy versus De-escalation to Monotherapy for Patients with MRSA Bacteremia

BackgroundPersistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with increased morbidity and mortality. Previous studies have demonstrated lower mortality with combination therapy (CT) compared to monotherapy (MT) for MRSA bacteremia; however, there is a lack of evidence to favor continued CT over de-escalation to MT for completion of treatment after clearance of bacteremia.MethodsThis was a single-center, retrospective study at The Ohio State University Wexner Medical Center in patients with MRSA bacteremia from November 2011 to July 2019. The primary composite outcome included inpatient infection-related mortality, 60-day readmission and 60-day bacteremia recurrence in patients receiving daptomycin and ceftaroline CT for greater than 10 days against those who received three to ten days of CT and were then de-escalated to either daptomycin, ceftaroline, or vancomycin MT. Statistical analysis used simple and multivariate logistic regression models to estimate crude and adjusted odds ratios and the 95% confidence interval to assess the relationship between the composite outcome for the MT and CT groups, while controlling for proven cofounders.ResultsA total of 286 patients with MRSA bacteremia were identified with 146 patients omitted based on exclusion criteria. The study population included 66 in the CT group and 74 in the MT group. Of those in the MT group 20 received ceftaroline, 29 received daptomycin, and 25 received vancomycin. Median age was 46 years (IQR 34.5–61), 60% required intensive care unit stay (n=84), and patients were 51% female (n=71) and 78% white (n=109). Bacteremia source was primarily intravenous drug use (40%) or line-related (16%). No significant difference was observed in the primary composite outcome (21% CT group vs 24% MT group; p=0.66). Within this outcome, there was no significant difference in readmission within 60 days (20% CT group vs 18% MT group; p=0.75), bacteremia recurrence within 60 days (3% CT group vs 7% MT group; p=0.45), or inpatient infection-related mortality (2% CT group vs 5% MT group; p=1.00). ConclusionNo significant difference was found in the composite clinical outcome for MRSA bacteremia patients with continued CT versus those who were switched to MT.Disclosures All Authors: No reported disclosures

106. Impact and Evaluation of BioFire® FilmArray® Respiratory Panel on Clinical Decision Making and Antibiotic Prescribing

BackgroundThe BioFire® FilmArray® respiratory panel (RFA) has been proposed as a tool for timely diagnosis and treatment of respiratory tract infections. However, the impact of the RFA on clinical decision making, most notably antibiotic prescribing, de-escalation and duration has been varied.MethodsWe aimed to determine the impact of RFA results on antibiotic days of therapy (DOT) depending on patient disposition. We conducted a retrospective chart review of adults who had an RFA performed within 48 hours of admission or presentation to the emergency departments (ED) of 3 hospitals in Des Moines, Iowa, between March 3 and March 16, 2019. Patients were excluded if they had a non-respiratory infection with defined indication for antibiotics. RFA results were categorized as influenza, non-influenza virus or negative. Negative binomial regression models were used to calculate rate ratios (RR) for the association between RFA result and DOT.ResultsA total of 486 total patients were included. Patients were divided according to disposition status, with 243 patients admitted and 243 discharged from the ED. Among inpatients, the median DOT was 2 (IQR 0–7). The results of the adjusted analysis for inpatient are shown on Table 1. In this group, RFA result was not associated with DOT (p=0.598 for non-influenza viruses and 0.706 for negative RFA), while having a urine culture done was independently associated with higher rate ratio of DOT (RR 1.85, 95% CI 1.32–2.59; p< 0.001). Among patients discharged from the ED, the median DOT was 0 (0–8). The results of the adjusted analysis for this group are shown on Table 2. Compared to patients with influenza, those with non-influenza viruses had a RR for DOT of 4.18 (95% CI 1.16–14.9; p=0.028) and those with a negative RFA had an RR for DOT of 5.24 (95% CI 1.99–13.8; p= 0.028).Adjusted analysis for the association between Respiratory Film Array results and Days of Therapy among hospitalized patients Adjusted analysis for the association between Respiratory Film Array Results and Days of Therapy among patients discharged from the ED ConclusionAmong inpatients, RFA results did not impact DOT, and in this group, antibiotic use was driven by urine cultures. In contrast, among patients discharged from the ED, a non-influenza virus or a negative RFA was associated with much higher rates of DOT. Our results suggest that different strategies need deployment in the ED compared to inpatient services in order to guide utilization of rapid molecular tests and antibiotic use.Disclosures All Authors: No reported disclosures

111. Impact of Microbiology Laboratory Result Presentation on Antibiotic Stewardship: Process Use Evaluation

BackgroundAdvancements in laboratory diagnostics are constantly occurring and accuracy in interpreting results directly affects optimal patient care. The purpose of this process use evaluation was to assess the efficacy of our current presentation of microbiology results in facilitating appropriate clinical decisions and antibiotic stewardship.MethodsA six question multiple choice survey was sent to prescribers and pharmacists. Each question used our healthcare system’s current presentation of microbiology results. The recipients were asked to make a clinical decision based on patient history and results presented. The topics surveyed included de-escalation of antibiotics based on polymerase chain reaction (PCR) for positive blood cultures (Image 1), evaluation of C. difficile PCR and enzyme immunoassays (Image 2), impact of recent immunization on results of S. pneumoniae urine antigen (Image 3), susceptibilities of Group C Streptococcus and H. influenzae (Images 4 and 5), and understanding of minimum inhibitory concentrations (MIC, Image 6). The anonymous surveys were collected either electronically or by paper.Image 1 Image 2 ResultsSeveral trends were seen in the 64 responses received (n, %). Questions with lab results containing detailed comments with guidance on how to interpret the results had the highest percentage of correct responses. This included our C. difficile (59, 92%) and S. pneumoniae urine antigen (61, 95%) results. Culture results with presumed susceptibilities and/or lack of guidance (H. influenzae (55, 86%); Group C Streptococcus (46, 72%)) had lower rates of correct interpretation and resulted in provider reluctance to de-escalate antibiotics. A similar trend was seen with the word “presumptive” on blood culture results by PCR (37, 58%). MICs were frequently misinterpreted as being able to compare activity between antibiotics (46, 72%).Image 3 Image 4 Image 5 ConclusionThis study highlights that stewardship programs should focus on how lab results are reported and interpreted and should work with their microbiology lab to determine the presentation of results. Additions of detailed interpretations to Microbiology results may lead to improved de-escalation and antibiotic selection.Image 6 Disclosures All Authors: No reported disclosures

97. Assessment of the accuracy of direct antimicrobial susceptibility testing from positive blood cultures in pediatric patients and its utility as an antimicrobial stewardship tool

BackgroundHospitalized pediatric patients with bacteremia receive broad-spectrum antibiotics while organism identification and antibiotic susceptibilities are pending. Direct susceptibility testing (DST) using unstandardized Kirby-Bauer disk diffusion provides early results before standardized (final) antimicrobial susceptibility testing (AST) is available. The accuracy of DST in comparison with AST has been poorly studied. If DST is highly accurate, it could facilitate earlier de-escalation of antibiotics.MethodsRetrospective cohort study of all positive blood cultures at Boston Children’s Hospital between January 1, 2017 and October 20, 2019. Isolates were eligible for inclusion if a DST result was available. Isolates were excluded if more than one organism grew from a blood culture or if a patient had repeat blood cultures positive for the same organism within 14 days. Patient characteristics and antibiotic orders were identified via a local data warehouse. Positive and negative predictive value (PPV: accuracy of susceptibility on DST in identifying susceptibility on AST result; NPV: accuracy of DST in identifying non-susceptibility on AST result) and 95% confidence interval were calculated for each bug-drug combination. Antibiotic Spectrum Index was evaluated at 3 time points to assess change in antibiotic prescribing after availability of DST and AST results.Results496 patients (median age: 51 months, IQR: 7–165 months) with 603 positive blood cultures were included in the final analysis. PPV of DST was ≥96%for most organism-antibiotic pairs (Table). NPV of DST varied substantially across organism-antibiotic pairs and was frequently lower than PPV. The proportion of patients with more narrow spectrum antibiotic orders increased after the DST result and again after the AST result (Figure).TableTest performance of direct susceptibility testing (DST) of clinical isolates from patients with bacteremia to identify organism susceptibility to the noted antibiotic. Positive predictive value measures the ability of a susceptible DST result to predict a susceptible AST result. Negative predict value measures the ability of an intermediate or resistant DST result to predict an intermediate or resistant AST result. *Includes Staphylococcus capitis, Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus pettenkoferi, and Staphylococcus warneri. ‡Includes Citrobacter freundii complex, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae complex, Escherichia coli, Escherichia vulneris, Klebsiella oxytoca, Klebseilla pneumoniae, Klebsiella variicola, Pantoea species, Proteus mirabilis, Salmonella species, Salmonella typhi, Serratia liquefaciens, and Serratia marcescens. FigureDistribution of spectrum of antibiotics ordered to treat bacteremia in pediatric patients. Antibiotic spectrum, as measured by the antibiotic spectrum index, is represented in this Sankey diagram on the Y-axis. The height of each group indicates the proportion of patients with an aggregate antibiotic spectrum falling in that category at three time points. The ASI of empiric antibiotics was measured just before the DST result to provide time for a treating physician to settle on an empiric regimen. The ASI with the DST result was measured just before the ASI result. The ASI with the AST result was measured 24 hours after the AST result was available. Green bars indicate the proportion of patients within a group whose ASI remained unchanged between time points. Blue bars indicate the proportion of patients within a group whose ASI decreased, and red bars indicate the proportion of patients whose ASI increased between time points. ConclusionDST is highly accurate at identifying susceptibility to antibiotics for many bug-drug combinations in pediatric blood culture isolates, but its ability to identify non-susceptibility is less robust. The observed spectrum of prescribed antibiotics was narrower after DST results, suggesting some clinicians may be using the result to de-escalate therapy. DST may be a useful low-cost tool for antimicrobial stewardship.Disclosures All Authors: No reported disclosures

208. Variation in Clinical Practice and Attitudes in the Management of Fever and Neutropenia in Patients With Hematologic Malignancy: A Survey of Cancer Centers Across the United States

BackgroundFever and neutropenia (FN) is common in cancer patients after chemotherapy, and there are national guideline recommendations for FN prevention and treatment. We conducted a survey of practices across multiple US cancer centers to determine the extent to which these guidelines have been adapted.MethodsUS cancer centers performing 20 allogeneic hematopoietic stem cell transplantations annually were identified from the National Marrow Donor Program’s “Be the Match” directory. Antimicrobial stewardship physicians and pharmacists at each institution were identified using institutional websites, residency or fellowship program directories, and personal contacts. A survey assessing institutional practices and individual attitudes on FN management in high-risk patients was distributed via email. Duplicate responses at the hospital level were removed. Complete surveys regarding individual attitudes were assessed using a 5-point Likert scale ranging from “Strongly Agree” to “Strongly Disagree.”ResultsThirty-four (23%) responses from 148 individuals were received, representing 31 of 86 hospitals (36%). 29 (94%) hospitals reported having guidelines for the management of FN. Of these, cefepime was the most commonly recommended agent for empiric treatment (26, 90%) and 16 (55%) provide guidance based on presumed site of infection. Eighteen (62%) hospitals recommend de-escalation of Gram negative therapy in certain situations, most often after being afebrile 48 – 72 hours or after neutrophil recovery (7 each, 39%). Twenty-seven (93%) hospitals recommended antibiotic prophylaxis, most often with levofloxacin (21, 78%). Of 34 respondents, attitudes were split regarding the statement “The benefit of antibiotic prophylaxis outweighs the harms in high-risk patients” (10 strongly agree or agree, 10 strongly disagree or disagree; 29% each); most agreed with the statement “I would use antibiotic prophylaxis in high-risk patients” (25, 78%).ConclusionMost cancer centers across the US have guidelines for the management of FN. While most recommend antibacterial prophylaxis, there were differences in individual perceptions regarding the risk / benefit. Significant variation exists in the approach to antibiotic de-escalation.Disclosures All Authors: No reported disclosures

86. Use of a Novel Clinical Decision Support Tool for Pharmacist-Led Antimicrobial Stewardship in Patients with Normal Procalcitonin

BackgroundOur Antimicrobial Stewardship Program (ASP) instituted review of patients on antibiotics with procalcitonin (PCT) < 0.25 mcg/L in 2012. In 2018, a clinical decision support (CDS) tool was implemented as part of a “daily checklist” for frontline pharmacists to assist in this patient review. We sought to validate the effectiveness of this tool for pharmacist-led PCT-based antibiotic stewardship.MethodsA retrospective cohort design was used to assess antibiotic de-escalation after PCT alert in patients on antibiotics for lower respiratory tract infections (LRTI). Secondary outcomes included antibiotic use and length of stay (LOS) in patients with PCT interventions vs those without.ResultsFrom 1/2019 to 11/2019, 652 of 976 (66.8%) PCT alerts were addressed by pharmacists. Of these, 331 were in patients with a respiratory-related diagnosis at discharge and 165 alerts were in patients on antibiotics specifically for LRTI over 119 encounters. Pharmacists made or attempted interventions after 34 (20.6%) of these alerts, with narrowing spectrum or converting to oral therapy being the most common interventions. Antibiotics were completely stopped in 4 of these interventions (11.8%). Patients with pharmacist intervention had 125 fewer antibiotic days of therapy (DOT) in the hospital, and changes were made to an additional 56 DOT (narrower therapy, IV to PO, dose optimization) following the alert. Two cases (5.9%) subsequently had therapy escalated within 48 hours. Vancomycin was the most commonly discontinued antibiotic with an 85.3% use reduction in patients with interventions compared to 27.4% discontinuation in patients with no documented intervention (p=0.0156). Alerts eligible for de-escalation but with no pharmacist intervention represented 140 DOT. LOS was similar in patients from both groups (median 6.4 days vs. 7 days, p=0.81).ConclusionInterventions driven by a CDS tool for pharmacist-driven antimicrobial stewardship in patients with normal PCT resulted in fewer DOT and significantly higher rates of vancomycin discontinuation. Additional interventions could have potentially prevented 140 DOT. We feel refinement of this tool can lead to more meaningful CDS, reduce alert fatigue, and likely increase intervention rates.Disclosures All Authors: No reported disclosures

96. Assessing the Impact of the Meningitis/encephalitis Diagnostic Panel on Antimicrobial Stewardship

BackgroundThe multiplex polymerase chain reaction (PCR) test for meningitis/encephalitis (ME) is an assay that is available to detect 14 organisms in 2 hours from the cerebral spinal fluid. The primary objective was to assess the clinical impact of this assay on antimicrobial stewardship.MethodsThis is an IRB-approved, retrospective cohort study of a random sample of patients admitted between 7/2015 - 12/2018, stratified by season. A chart review was performed to collect: demographics, microbiology/treatment data, length of stay, hospital readmissions, and mortality. Differences for ME PCR versus culture only were assessed using Chi-square test or Fisher’s exact test. Time to de-escalation of empiric therapy was compared using the log-rank test.ResultsThe study consisted of 241 patients, of whom 161 (66.8%) had CSF-PCR testing performed. Mean age was 51.76. There was an even distribution of males and females. Aside from patients with HIV, who were more represented in the standard period, there were no differences by comorbidity. The etiology of meningitis was greater in the PCR compared to the non-PCR group (10.5% vs. 2.5% in PCR and non-PCR respectively). Time to de-escalation of empiric therapy was significantly shorter in the PCR period (median [IQR]: 43.06 [26.9–47.7] vs. 64.62 [37.18–83.33], P< 0.004). Total days of therapy of antibiotics was longer among the PCR group, but not statistically significant (median [IQR] = 4 [1–7] vs. 2 [1–4], P=0.121). Median length of stay was higher in the PCR period compared to the standard group (median [IQR]: 9 [6 - 15] vs. 5.5 [3 - 8.5], P< 0.004). Readmission rates did not differ (PCR 13.7% vs. non-PCR 16.3%, P=0.592). More died during the PCR period (8.6% vs. 3.8%, P=0.16) but this was not statistically significant.ConclusionThe ME PCR was associated with an earlier time to antibiotics de-escalation. Patients that had the PCR test performed had more days of therapy and longer length of stay, but this is likely due to a higher rate of pathogen diagnosed. There was no association in readmissions. The initiation of rapid diagnostic testing in a healthcare settings has the potential to improve patient outcomes and may help antimicrobial stewardship by shortening the time to de-escalating antimicrobials and offering appropriate targeted therapy.Disclosures All Authors: No reported disclosures

1227: Procalcitonin-Guided Antibiotic De-Escalation in Septic ICU Patients in a Veterans Affairs Hospital

1227: Procalcitonin-Guided Antibiotic De-Escalation in Septic ICU Patients in a Veterans Affairs Hospital

1224: Impact of Antibiotic De-Escalation in Critically Ill Patients With Culture-Negative Sepsis

1224: Impact of Antibiotic De-Escalation in Critically Ill Patients With Culture-Negative Sepsis

Utility of the respiratory viral panel as an antimicrobial stewardship tool.

The development of rapid diagnostics has revolutionized antimicrobial stewardship with efforts targeting earlier de-escalation or discontinuation of antibiotics. The respiratory viral panel (RVP) is one tool quickly able to detect common viral and bacterial pathogens using polymerase chain reaction technology. Utility may be further enhanced in conjunction with procalcitonin (PCT). However, the optimal use of the RVP to the clinical pharmacist in the treatment of community-acquired respiratory infections remains unclear. The purpose of this guide is to review the available literature regarding the impact of the RVP with and without procalcitonin on antimicrobial stewardship efforts and to provide guidance on how to use each of these tools. In total, 13 studies were included, 5 of which utilized PCT in conjunction with RVP and 8 of which did not use PCT. The majority of studies were retrospective in nature, and the most common outcomes evaluated were antibiotic days of therapy (DOT) and time to antibiotic discontinuation. After review, RVP alone has limited value to antimicrobial stewardship; however, when used in conjunction with procalcitonin, RVP has the potential to reduce antibiotic use and duration.

Evaluation on the impact of antimicrobial stewardship programme (AMS) in a tertiary hospital

Background: Antimicrobial Resistance (AMR) is a serious threat to global public health. Hence, in Malaysia, Antimicrobial Stewardship (AMS) was developed to optimize antimicrobial use in health care setting. Not many studies have been conducted and the impact of AMS in Hospital Serdang is unknown. This study was conducted to assess the impact of antimicrobial stewardship in Hospital Serdang. Methods and materials: Prospective observational cross-sectional study. Universal sampling where all patients intervened during AMS round (patient empirically started on carbapenem, vancomycin, and polymyxin B & E) in study period from 1st January 2017 to 31st December 2017. Patient's data were retrieved from the electronic hospital information system (eHIS) and ward medication charts. Clinical outcome includes clinical cure rate, discharged alive, mortality rate, readmission rate and length of stay were evaluated. Results: A total of 142 patients intervened in the AMS round throughout the study period. Majority of the patients were male (60.6%), mean age 54.1 years, with comorbidities (77.5%) and most of the antibiotics were initiated for respiratory tract infections (39.4%). Similar clinical cure rate (46.3% vs. 42.1%), discharged alive rate (72.4% vs. 73.7%) and mortality rate (27.6% vs. 26.3%) were demonstrated between interventions accepted group and rejected group. Readmission rate were 8.9% among accepted group and no readmission was reported in rejected group. De-escalation of antibiotic (42%) was the most common interventions accepted. This was followed by escalation of antibiotic, inappropriate choice of antibiotic, inappropriate dose, inappropriate duration, polypharmacy and inappropriate frequency. High acceptance rate (86.6%) of AMS interventions were demonstrated in this study. Conclusion: Implementation of AMS helps to guide physician in optimizing the appropriate use of antimicrobial therapy in healthcare setting.

Clinical assessment of the utility of metagenomic next-generation sequencing in pediatric patients of hematology department.

Metagenomic Next-Generation Sequencing (mNGS) is an emerging technique for microbial identification and diagnosis of infectious diseases. The clinical utility of mNGS, especially its real-world impact on antimicrobial treatment and patient outcome has not been systematically evaluated. We prospectively assessed the effectiveness of mNGS in 70 febrile inpatients with suspected infections at Hematology department of the Children's Hospital, National Clinical Research Center for Child Health. 69/70 patients were given empirical antibiotics prior to mNGS. A total of 104 samples (62 plasma, 34 throat swabs, 4 bone marrow, 4 bronchoalveolar lavage) were collected on day 1-28 (mean 6.9) following symptom onset and underwent mNGS testing. Traditional microbiological tests discovered causal microorganisms in 5/70 (7.14%) patients, which were also detected by mNGS. In addition, mNGS reported possible pathogens when routine tests were negative. Antibiotics were adjusted accordingly in 55/70 (78.6%) patients that led to improvement/relief of symptoms within 3days. In contrast, mNGS results were considered irrelevant in 15/70 (21.4%) patients by a board of clinicians, based on biochemical, serological, imaging evidence, and experiences. mNGS expanded the capacity of pathogen detection and made a positive impact on clinical management of suspected infections through (a) differential diagnosis which may rule out infectious diseases and (b) adjustment or de-escalation of empirical antibiotics.

Why Vancomycin Is Overly Prescribed Despite the Lack of Supporting Microbiological Data

Objective To develop a concept map in order to evaluate the factors associated with continuing of vancomycin after 48 to 72 hours of prescription despite the lack of supporting microbiological data. Methods This study was conducted in a teaching hospital affiliated to Mashhad University of Medical Sciences, Iran, between January 2017 and March 2017. After demonstrating the high rate of overuse and inappropriate use of vancomycin in our teaching hospital in the first arm of the study, we attempted to evaluate the factors associated with this behavior by developing a concept map. In this study, cluster approach of concept mapping was used and the importance of statements was scored by using the 5-point Likert method (1 for the lowest score and 5 for the highest score). Results Twenty-one physicians were participated, with a male to female ratio of 2. During the brainstorming session, about 25 statements were generated, which eventually resulted in sorting of 16 appropriate statements. The highest scored statements for continuing vancomycin after 48 to 72 hours of prescription in the absence of supporting microbiological data was worries and concerns of physicians regarding critically ill status of patients (score, 3.76) and lack of updated information on microbiological spectrum and antimicrobial resistance pattern of infections at the regional level (score, 3.57). In the final cluster analysis, the mean of importance of a cluster consisted of “health care system-physician related factors” was scored highest (score, 3.2), as compared with other created clusters. Conclusions According to the result of our study, improving vancomycin use requires more effective education of basic principles of diagnosis of infectious clinical syndromes and the concept of deescalation of antibiotics. It should also address physicians' concerns about the management of critically ill septic patients. In addition, providing the physicians with updated information on microbiological spectrum and antimicrobial resistance pattern of infections at the regional level can be effective in improving vancomycin prescription behavior.

Time to First Culture Positivity for Gram-Negative Rods Resistant to Ceftriaxone in Critically Ill Adults.

The optimal timing for the de-escalation of broad-spectrum antibiotics with activity against Pseudomonas aeruginosa and resistant Gram-negative rods (GNRs) in critically ill adults remains unknown. We tested the hypothesis that cultures will identify GNRs that ultimately demonstrate resistance to ceftriaxone within 48 hours, potentially allowing safe de-escalation at this time point. We conducted a secondary analysis of data from the Isotonic Solutions and Major Adverse Renal Events Trial: a pragmatic, cluster-randomized, multiple-crossover trial comparing balanced crystalloids versus saline for intravenous fluid administration in 15,802 critically ill adults at 5 intensive care units (ICUs) at Vanderbilt University Medical Center in Nashville, TN, USA. The primary endpoint was the time-to-positivity of respiratory and blood cultures that ultimately demonstrated growth of GNRs resistant to ceftriaxone. Multivariable logistic regression modeling was used to examine risk factors for the growth of cultures after 48 hours. A total of 524 respiratory cultures had growth of GNRs, of which 284 (54.2%) had resistance to ceftriaxone. A total of 376 blood cultures grew GNRs, of which 70 (18.6%) had resistance to ceftriaxone. At 48 hours, 87% of respiratory cultures and 85% of blood cultures that ultimately grew GNRs resistant to ceftriaxone had demonstrated growth. Age, gender, predicted risk of inpatient mortality and prior use of antibiotics did not predict the growth of cultures after 48 hours. Among a cohort of critically ill adults, 13% of respiratory cultures and 15% of blood cultures that ultimately grew GNRs resistant to ceftriaxone did not demonstrate growth until at least 48 hours after collection. Further work is needed to determine the ideal time for critically ill adults to de-escalate from broad-spectrum antibiotics targeting Pseudomonas aeruginosa and extended-spectrum β-lactamase-producing gram-negative pathogens.