1505. Antiviral and Antibiotic Prescribing Among Patients at an Ambulatory Cancer Center with Laboratory-Confirmed Influenza

Abstract Background Cancer patients are at high risk for serious complications due to influenza. Early treatment with neuraminidase inhibitors (NAIs) is recommended for high-risk patients with suspected or documented influenza. Limited data exist on timing of presentation to care and ambulatory management of cancer patients with influenza. We sought to characterize antimicrobial prescribing and outcomes among patients with influenza at a large cancer center. Methods We selected consecutive patients seen in the ambulatory cancer clinic with laboratory confirmed influenza between January 1, 2016 and December 31, 2018 for chart review. A lab-developed multiplex PCR assay was used with a turnaround time of about 24 hours. We obtained demographics, symptoms at first clinic encounter (day 0), viral testing, NAI and antibiotic prescribing, and clinical outcomes. Results Of 138 charts reviewed, 133 (96%) were eligible for analysis. 109 (82%) had an underlying hematologic malignancy. 84 (63%) tested positive for influenza A and 49 for influenza B. 58 (44%) presented to care within 48 hours of symptom onset (F1). The most commonly reported symptoms were cough (83%), fever (41%), and rhinorrhea (40%) (F2). 110 (83%) were prescribed oseltamivir, with 24 (22%) receiving empiric therapy on day 0, and 63 (57%) prescribed on day 1 (F3). Among 109 patients with known symptom onset date, 34 (31%) were prescribed oseltamivir within 48 hours of symptom onset. 23 (17.3%) were prescribed antibiotics, 17 (74%) on day 0 (F3). Levofloxacin (26%), azithromycin (21%) and vancomycin (18%) were most commonly prescribed. Nine (6.8%) patients progressed to lower respiratory tract infection, 1 complicated by bacterial pneumonia. There were 11 (8.3%) influenza-related hospitalizations, 1 (0.7%) ICU admission, and no influenza-related deaths. Figure 1. Time From Symptom Onset to Date of First Clinical Encounter Figure 2. Symptoms Reported at First Clinical Encounter Figure 3. Time from First Clinical Encounter to Oseltamivir and Antibiotic Prescription Conclusion NAIs were frequently prescribed among cancer patients, but less than a third received treatment within 48 hours of symptom onset. Most were prescribed NAIs only after test results were available, while antibiotics were prescribed empirically. Delayed presentation to care is an obstacle to early NAI use; patient and provider education along with rapid diagnostics are needed to improve early NAI use among cancer patients with influenza. Disclosures Steven A. Pergam, MD, MPH, Chimerix, Inc (Scientific Research Study Investigator)Global Life Technologies, Inc. (Research Grant or Support)Merck & Co. (Scientific Research Study Investigator)Sanofi-Aventis (Other Financial or Material Support, Participate in clinical trial sponsored by NIAID (U01-AI132004); vaccines for this trial are provided by Sanofi-Aventis)

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273. Comparative Effectiveness of Ampicillin in the Treatment of Enterococcus faecalis Bloodstream Infections in Patients With Cancer

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.317 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S137-S138

Author(s):

J P Sanchez ◽

German Contreras ◽

Truc T Tran ◽

Shelby Simar ◽

Blake Hanson ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Kidney Injury ◽

Bloodstream Infections ◽

Definitive Treatment ◽

Cancer Center ◽

Future Research ◽

Research Support ◽

Patients With Cancer ◽

Study Investigator

Abstract Background E. faecalis (Efc) isolates are usually susceptible to ampicillin (AMP). AMP-based regimens are the standard of care for enterococcal infections, although other antibiotics are often used as definitive treatment. We thus compared outcomes of patients with cancer and Efc bacteremia treated with AMP-containing (ACR) and non-AMP-containing antibiotic regimens (NACR). Methods A multicenter, prospective, observational cohort study conducted at MD Anderson Cancer Center, Henry Ford Hospital, and Memorial Hermann Health System. Eligible patients were ≥ 18 years old, diagnosed with cancer, and had at least one Efc bloodstream isolate collected from 12/2015 to 12/2018. Patients with polymicrobial infections were excluded. Patients were divided into two groups: i) ACR and ii) NACR. ACR included patients who received AMP at any time during treatment; other antimicrobials were permitted. NACR patients did not receive AMP at any time. The primary outcome compared desirability of outcome ranking (DOOR) between ACR and NACR at day 14. The DOOR consisted of six hierarchical levels: 1 - death; 2 - inpatient without microbiological cure (MC) and with acute kidney injury (AKI); 3 - inpatient without MC and without AKI; 4 - inpatient admitted with MC and with AKI; 5 - inpatient with MC and without AKI; 6 - alive and discharged. Comparison of DOORs between ACR and NACR was performed using inverse probability of treatment weighted (IPTW) ordered logistic regression. Results Seventy-one patients were included (ACR, n = 35; NACR, n = 36). No difference was seen in DOORs at day 14 between ACR and NACR (odds ratio [OR] 1.14, 95% Confidence Interval [CI] 0.45 – 2.92, p=0.78). No difference was observed for all-cause mortality at day 14 (OR 0.6, 95% CI 0.09 – 3.77, p=0.58) or day 30 (OR 0.42, 95% CI 0.09 – 1.94, p=0.27). Patients treated with ACR received a lower median duration of other antibiotics at any point during treatment compared to NACR: daptomycin (2 v 4 days) vancomycin (2 v 4 days), and linezolid (1 v 2 days). Conclusion Patients with cancer and Efc bloodstream infections had similar outcomes when treated with ACR and NACR. ACR were associated with less use of broad-spectrum antimicrobials. Future research should focus on the ecologic impact of use of NACR. Disclosures Marcus Zervos, MD, Melinta Therapeutics (Grant/Research Support) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

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LB1. Remdesivir for the Treatment of High-Risk Non-Hospitalized Individuals With COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1642 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S806-S807

Author(s):

Joshua A Hill ◽

Roger Paredes ◽

Carlos Vaca ◽

Jorge Mera ◽

Brandon J Webb ◽

...

Keyword(s):

High Risk ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Double Blind ◽

Material Support ◽

Double Blind Placebo ◽

Study Investigator

Abstract Background Remdesivir (RDV) is a potent nucleotide prodrug inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase that has demonstrated efficacy in the treatment of patients hospitalized with moderate to severe COVID-19. This Phase 3 (GS-US-540–9012) double-blind, placebo-controlled study compared the efficacy and safety of 3 days of RDV to standard of care in non-hospitalized, high-risk participants with confirmed COVID-19. Table 1. COVID-19 related hospitalization or death, COVID-19 related medically attended visits or death, and Treatment Emergent Adverse Events Methods Participants were randomly assigned 1:1 to receive intravenous (IV) RDV (200 mg on day 1, 100 mg on days 2 to 3) or placebo. The primary efficacy endpoint was composite COVID-19 hospitalization or all-cause death by day 28 and compared using Cox proportional hazards model with baseline stratification factors as covariates. The primary safety endpoint was proportion of participants with treatment-emergent adverse events. Study enrollment was terminated early for administrative reasons in light of the evolving pandemic. Results 562 patients underwent randomization and started their assigned treatment (279, RDV; 283, placebo). Baseline demographics and characteristics were balanced across arms. Overall, 52% were male, 44% were Hispanic/Latino ethnicity and 30% were ≥ 60 years old. The most common comorbidities were diabetes mellitus (62%), obesity (56%; median BMI, 30.7), and hypertension (48%). Median baseline SARS-CoV-2 RNA nasopharyngeal viral load was 6.2 log10 copies/mL. Treatment with RDV significantly reduced COVID-19 hospitalization or all-cause death by day 28 (HR, 0.13; 95% CI, 0.03 – 0.59; p = 0.008; Table 1) compared to placebo. Participants receiving RDV also had significantly lower risk for COVID-19-related medically attended visits or all-cause death by day 28 compared to placebo (HR, 0.19; 95% CI, 0.07 – 0.56; p = 0.002; Table 1). No deaths occurred in either arm by day 28. There was no difference between arms in time-weighted average change in nasopharyngeal viral loads from baseline up to day 7. The proportion of patients with AEs was similar between arms (Table 1); the most common AEs in the RDV arm were nausea (11%), headache (6%), and diarrhea (4%). Conclusion A 3-day course of IV RDV was safe, well tolerated and highly effective at preventing COVID-19 related hospitalization or death in high-risk non-hospitalized COVID-19 patients. Disclosures Joshua A. Hill, MD, Allogene (Individual(s) Involved: Self): Consultant; Allovir (Individual(s) Involved: Self): Consultant, Grant/Research Support; Amplyx (Individual(s) Involved: Self): Consultant; Covance/CSL (Individual(s) Involved: Self): Consultant; CRISPR (Individual(s) Involved: Self): Consultant; Gilead (Individual(s) Involved: Self): Consultant, Grant/Research Support; Karius: Grant/Research Support, Scientific Research Study Investigator; Medscape (Individual(s) Involved: Self): Consultant; Octapharma (Individual(s) Involved: Self): Consultant; OptumHealth (Individual(s) Involved: Self): Consultant; Takeda (Individual(s) Involved: Self): Consultant, Grant/Research Support, Scientific Research Study Investigator Roger Paredes, MD, PhD, Gilead Sciences, Inc (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Carlos Vaca, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Jorge Mera, MD, Gilead Sciences, Inc (Consultant, Study Investigator (payment to employer not self)) Gilberto Perez, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Godson Oguchi, MD, Gilead Sciences, Inc (Scientific Research Study Investigator) Pablo Ryan, MD PhD, Gilead Sciences, Inc (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member) Jan Gerstoft, MD, Gilead Sciences, Inc (Other Financial or Material Support, Study Investigator (payment to employer)) Michael Brown, FRCP PhD, Gilead Sciences, Inc (Scientific Research Study Investigator, Investigator for numerous remdesivir trials (employer received compensation)) Morgan Katz, MD, MHS, Roche (Individual(s) Involved: Self): Advisor or Review Panel member; Skinclique (Individual(s) Involved: Self): Consultant Gregory Camus, PhD, Gilead Sciences (Employee, Shareholder) Danielle P. Porter, PhD, Gilead Sciences (Employee, Shareholder) Robert H. Hyland, DPhil, Gilead Sciences, Inc (Shareholder, Other Financial or Material Support, Employee during the conduct of this trial) Shuguang Chen, PhD, Gilead Sciences, Inc (Employee, Shareholder) Kavita Juneja, MD, Gilead Sciences, Inc (Employee) Anu Osinusi, MD, Gilead Sciences, Inc (Employee, Shareholder) Frank Duff, MD, Gilead Sciences, Inc (Employee, Shareholder) Robert L. Gottlieb, MD, Eli Lilly (Scientific Research Study Investigator, Advisor or Review Panel member)Gilead Sciences (Scientific Research Study Investigator, Advisor or Review Panel member, Other Financial or Material Support, Gift in kind to Baylor Scott and White Research Institute for NCT03383419)GSK (Advisor or Review Panel member)Johnson and Johnson (Scientific Research Study Investigator)Kinevant (Scientific Research Study Investigator)Roche/Genentech (Scientific Research Study Investigator)

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178. Vaccine Effectiveness Against Influenza-associated Hospitalizations and Emergency Department (ED) Visits Among Children in the United States in the 2019–2020 Season

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.488 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S217-S218

Author(s):

Angela P Campbell ◽

Constance E Ogokeh ◽

Geoffrey A Weinberg ◽

Julie A Boom ◽

Janet A Englund ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Influenza B ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Influenza A H1n1 ◽

Ed Visits ◽

Research Grant

Abstract Background The 2019–20 influenza season was predominated by early onset B/Victoria viruses followed by A(H1N1)pdm09 virus circulation. Over 95% of circulating B/Victoria viruses were subclade V1A.3, different from the Northern Hemisphere vaccine strain. Annual estimates of influenza vaccine effectiveness (VE) are important because of frequent changes in circulating and vaccine viruses. Methods We assessed VE among children 6 months–17 years old with acute respiratory illness and <10 days of symptoms enrolled during the 2019–20 influenza season at 7 pediatric hospitals (ED patients < 5 years at 3 sites) in the New Vaccine Surveillance Network. Combined mid-turbinate/throat swabs were tested for influenza virus using molecular assays. We estimated age-stratified VE from a test-negative design using logistic regression to compare odds of vaccination among children testing positive versus negative for influenza, adjusting for age in years, enrollment month, and site. For these preliminary analyses, vaccination status was by parental report. Results Among 2022 inpatients, 324 (16%) were influenza positive: 38% with influenza B/Victoria alone and 44% with influenza A(H1N1)pdm09 alone (Table). Among 2066 ED children, 653 (32%) were influenza positive: 45% with influenza B/Victoria alone and 43% with influenza A(H1N1)pdm09 alone. VE was 62% (95% confidence interval [CI], 51%–70%) against any influenza-related hospitalizations, 68% (95% CI, 55%–78%) for A(H1N1)pdm09 and 55% (95% CI, 35%–69%) for B/Victoria. VE by age group for any influenza-related hospitalizations was 57% (95% CI, 40%–69%) among children 6 months to < 5 years and 66% (95% CI, 49%–77%) among children 5–17 years. VE was 53% (95% CI, 42%–62%) against any influenza-related ED visits, 46% (95% CI, 28%–60%) for A(H1N1)pdm09 and 54% (95% CI, 39%–66%) for B/Victoria. VE by age group was 52% (95% CI, 37%–63%) among children 6 months to < 5 years and 42% (95% CI, 16%–60%) among children 5–17 years. Conclusion Influenza vaccination in the 2019–20 season provided substantial protection against laboratory-confirmed influenza-associated hospitalizations and ED visits associated with the two predominantly circulating influenza viruses among children, including against the emerging B/Victoria virus V1A.3 subclade. Disclosures Janet A. Englund, MD, AstraZeneca (Scientific Research Study Investigator)GSK group of companies (Scientific Research Study Investigator)Meissa vaccines (Consultant)Merck (Scientific Research Study Investigator)Sanofi Pasteur (Consultant) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (Advisor or Review Panel member) Natasha B. Halasa, MD, MPH, Genentech (Other Financial or Material Support, I receive an honorarium for lectures - it’s a education grant, supported by genetech)Karius (Consultant)Moderna (Consultant)Quidel (Grant/Research Support, Research Grant or Support)Sanofi (Grant/Research Support, Research Grant or Support) Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial)

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1076. Gaps in Measles and Mumps Seroprevalence Among Cancer Patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1262 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S565-S566

Author(s):

Sara Marquis ◽

Jennifer Logue ◽

Tillie Loeffelholz ◽

Z Z Quinn ◽

Catherine Liu ◽

...

Keyword(s):

Cancer Patients ◽

Research Study ◽

Hematologic Malignancy ◽

Multivariable Analysis ◽

Scientific Research ◽

Current Status ◽

Cell Transplant ◽

Research Support ◽

Study Investigator ◽

Increased Risk

Abstract Background Immunosuppressed cancer patients are at risk for morbidity and mortality from vaccine preventable diseases. Recent outbreaks and declining vaccination rates put cancer patients at increased risk for measles and mumps exposures. To assess the current status within our center, we measured measles and mumps seroprevalence among cancer patients. Methods Residual clinical plasma samples from patients seen at Seattle Cancer Care Alliance were collected between 8/11/2019 and 8/15/2019 and tested for measles and mumps IgG using ELISA (Genway Biotech); patients receiving intravenous immunoglobulin ≤16 weeks prior to collection date were excluded. Seroprevalence was calculated based on positive results; equivocal results were not considered protective. Demographic and clinical data were abstracted from medical records. Overall and subgroup seroprevalence were estimated with Wilson 95% confidence intervals (CI); Poisson regression with robust standard errors was used to compare subgroups and estimate prevalence ratios (PR). Results Of 1000 unique patients, 987 were eligible, with a median age of 61 years (range 2-97). More than half had a solid tumor (574 [58%]) while 376 (38%) had a hematologic malignancy (HM); 155 (16%) were hematopoietic cell transplant (HCT) recipients. The percentage of seropositive patients was 75% (95% confidence interval [CI]: 72%, 78%) for measles and 62% (95% CI: 59%, 65%) for mumps. Seropositivity was highest among older age groups, particularly those older than 63, who most likely have naturally acquired immunity (Figure 1-2). In multivariable analysis, patients aged 30-59 years were significantly less likely to be seropositive compared to patients ≥80 years of age. Patients with HM and those undergoing HCT were also less likely to be seropositive (Figure 3). Figure 1. Distribution of age at sample collection and measles antibody test results Figure 2. Measles and mumps seroprevalence by age Figure 3. Multivariable model estimates for measles and mumps seroprevalence Conclusion One-quarter of cancer patients tested did not have evidence of seroprotection for measles and mumps. Seronegative and equivocal responses were observed primarily among younger patients and those with hematologic malignancies. Deficits in protective antibody seen in this study are common among cancer patients and underscore the need for population/community-based efforts to increase herd immunity and protect vulnerable populations. Disclosures Helen Y. Chu, MD MPH, Cepheid (Grant/Research Support)Ellume (Grant/Research Support)Glaxo Smith Kline (Consultant)Merck (Consultant)Sanofi-Pasteur (Grant/Research Support) Steven A. Pergam, MD, MPH, Chimerix, Inc (Scientific Research Study Investigator)Global Life Technologies, Inc. (Research Grant or Support)Merck & Co. (Scientific Research Study Investigator)Sanofi-Aventis (Other Financial or Material Support, Participate in clinical trial sponsored by NIAID (U01-AI132004); vaccines for this trial are provided by Sanofi-Aventis)

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1514. Mortality and Readmission in Adults during the First Year Following Hospitalization for Community-Acquired Pneumonia in the US

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1695 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S760-S760

Author(s):

Reiko Sato ◽

Derek Weycker ◽

Melody Shaff ◽

Ahuva Hanau ◽

Alexander Lonshteyn ◽

...

Keyword(s):

At Risk ◽

High Risk ◽

Hospital Readmission ◽

Research Study ◽

Scientific Research ◽

Research Support ◽

Post Discharge ◽

Study Investigator ◽

Comorbidity Profile ◽

Research Grant

Abstract Background Increasing evidence suggests that the impact of community-acquired pneumonia (CAP) extends beyond discharge from the hospital and the acute phase of illness. We sought to characterize mortality and hospital readmission across the adult age span and spectrum of comorbidities. Methods A retrospective cohort design and data from Optum’s de-identified Integrated Claims-Clinical dataset (2009-2018) were employed. Study population comprised all adults who, between 1.1.2013 and 12.31.2017, had ≥ 1 acute-care hospitalization for CAP; each qualifying CAP hospitalization separated by ≥ 365 days was included as a unique observation in analyses. Study outcomes included acute-care hospital readmission for any reason and death for any reason. Hospital readmission was ascertained during the 360-day period following discharge from the CAP hospitalization; death was ascertained during the CAP hospitalization as well as during the same 360-day period. Cumulative rates of mortality and readmission were summarized for all patients as well as subgroups defined on age and comorbidity profile (i.e., healthy, at-risk, high-risk). Results Study population totaled 37,006 patients who contributed 38,809 CAP hospitalizations; mean age was 71 years, 51% were female, and 88% had an at-risk (33%) or high-risk (55%) condition. Hospital readmission was 12.5% during the 30-day post-discharge period, and 42.3% during the 360-day post-discharge period. Mortality was 3.5% in hospital, 8.2% from admission to 30 days post-discharge, and 17.7% from admission to 360 days post-discharge. Mortality rates increased with age and severity of comorbidity profile; readmission rates were highest for persons aged 65-74 years and high-risk persons. Rates of readmission and mortality among adults hospitalized for CAP Conclusion All-cause mortality up to 1 year following hospital admission for CAP was substantial, and was associated with increasing age and worsening comorbidity profile. Both readmission and mortality were greater at all ages in high-risk and at-risk groups compared with their healthy counterparts. Strategies that prevent pneumonia and/or the pathophysiologic changes that follow CAP, especially among individuals with comorbid conditions, have the potential to reduce morbidity and mortality following CAP as well as healthcare costs associated with readmission. Disclosures Reiko Sato, PhD, Pfizer, Inc (Employee, Shareholder) Derek Weycker, PhD, Pfizer Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Melody Shaff, BA, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Ahuva Hanau, BS, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Alexander Lonshteyn, PhD, Pfizer, Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Stephen I. Pelton, MD, Merck vaccine (Consultant, Grant/Research Support)Pfizer (Consultant, Grant/Research Support)Sanofi Pasteur (Consultant, Other Financial or Material Support, DSMB)Seqirus Vaccine Ltd. (Consultant)

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281. Detecting bacterial sepsis among allogeneic HCT recipients with population-specific bedside tools

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.325 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S140-S141

Author(s):

Margaret Lind ◽

Steven A Pergam ◽

Catherine Liu ◽

Amanda Phipps ◽

Stephen Mooney ◽

...

Keyword(s):

High Risk ◽

Research Study ◽

Rare Event ◽

Scientific Research ◽

Early Warning Score ◽

High Risk Population ◽

Cell Transplant ◽

Bacterial Sepsis ◽

Prediction Tools ◽

Study Investigator

Abstract Background Diagnosing sepsis among allogeneic hematopoietic cell transplant (aHCT) recipients remains challenging. Existing criteria, for use in hospitalized patients, have limited predictive accuracy among aHCT recipients and their use may lead to missed events or antibiotic overuse. We developed bedside bacterial sepsis prediction tools (criteria and decision tree [DT]) for aHCT recipients and compared them against Systemic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score (NEWS) criteria. Methods Adult aHCT recipients transplanted between September 2010–2019 with ≥ 1 potential infection (PI) within 100 days post-transplantation were randomly assigned to model/validation (7/3) cohorts. Tools included demographic and clinical factors and were built against a bacterial sepsis endpoint (gram-negative, Staphylococcus aureus, or Streptococcus species bacteremia). The tools were developed using best subset selection with rare event logistic regression (criteria) and classification tree (DT) algorithms. Criteria scores were estimated using a beta/10 integer weighting approach and tool predictive performances were compared against existing criteria. Results Between September 2010–2019, 1571 recipients with ≥ 1 PI contributed 7755 PIs and 238 sepsis events. The DT model included 7 terminal nodes based on 3 predictors: temperature, respiratory rate (RR), and sex. The criteria model contained 10 categories with 4 predictors: RR, temperature, pulse, and diastolic blood pressure (Figure 1). Our criteria and DT had AUCs of 71.1% (95% Confidence Interval (CI): 64.3, 77.9%) and 70.0% (CI: 63.7, 76.2%). SIRS had the highest AUC of existing criteria – 64.7% (CI: 57.1, 71.9%). Our criteria had the highest net benefit (for probabilities < 10%) and, at a 7+ cut-point, had a sensitivity of 73.8% (CI: 61.5–84.0%) and specificity of 55.0% (CI: 52.9, 57.1%) (Figure 2). Conclusion We developed aHCT recipient-specific bedside bacterial sepsis prediction tools with higher AUCs than existing criteria. Tools targeted to high-risk populations may lead to fewer missed sepsis events and, in turn, reduce sepsis related mortality among this high-risk population. Disclosures Steven A. Pergam, MD, MPH, Chimerix, Inc (Scientific Research Study Investigator)Global Life Technologies, Inc. (Research Grant or Support)Merck & Co. (Scientific Research Study Investigator)Sanofi-Aventis (Other Financial or Material Support, Participate in clinical trial sponsored by NIAID (U01-AI132004); vaccines for this trial are provided by Sanofi-Aventis)

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26. Factors Associated with Meningococcal Vaccination among Patients with Newly Diagnosed High-Risk Conditions

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.071 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S37-S37

Author(s):

Parinaz Ghaswalla ◽

Lindsay Bengtson ◽

Gary S Marshall ◽

Ami R Buikema ◽

Tim Bancroft ◽

...

Keyword(s):

High Risk ◽

Index Date ◽

Research Study ◽

Scientific Research ◽

Administrative Claims ◽

Pneumococcal Vaccines ◽

Research Database ◽

Newly Diagnosed ◽

Factors Associated ◽

Study Investigator

Abstract Background Vaccination is recommended for persons at increased risk for invasive meningococcal disease (IMD) due to complement component deficiency (CD), asplenia or human immunodeficiency virus (HIV) infection. However, uptake of quadrivalent conjugate and polysaccharide meningococcal vaccines (MenACWY) one year following a new high-risk diagnosis is very low (doi:10.1093/ofid/ofz360.2403). This retrospective cohort study identified factors associated with MenACWY vaccination among patients newly diagnosed with CD or HIV. Methods Patients identified from a large US commercial administrative claims database (Optum Research Database) with continuous enrollment for ≥12 months before and ≥6 months after appearance of an incident high-risk diagnosis through the end of the study period (3/31/2018) were considered eligible (Figure). Cox proportional hazards regression models were used to identify characteristics associated with time to receipt of ≥1 dose of MenACWY during time periods corresponding with Advisory Committee on Immunization Practices (ACIP) recommendations. Results The CD cohort consisted of 1,470 (mean=40.9 years of age) patients and the HIV cohort of 1,208 (38.8 years). Only 7.9% and 20.8% of patients with CD or HIV, respectively, received ≥1 dose of MenACWY between their index date and the end of the study period. A strong association between receipt of MenACWY and pneumococcal vaccines was seen for CD [hazard ratio (HR): 3.2; 95% CI: 1.8–5.7] and HIV [23.0; 13.9–38.1]. Age (11–18 years; for CD only) and having a well-care visit after the index date (for CD and HIV) was associated with higher likelihood of vaccination. Vaccination rates for HIV were lowest in the South. Conclusion The association of MenACWY vaccination with age in patients with CD suggests confusion between routine age-based and high-risk recommendations, whereas in patients with CD or HIV, the association with pneumococcal vaccines suggests that providers recognize the overlap in risk factors for IMD and pneumococcal disease. Ensuring healthcare access for these vulnerable patients and educating providers about high-risk recommendations is crucial. Funding GlaxoSmithKline Biologicals SA (study identifier: HO-18-19581) Disclosures Parinaz Ghaswalla, PhD, ORCID: 0000-0002-2883-5590, GlaxoSmithKline (Employee, Shareholder) Lindsay Bengtson, PhD, MPH, Optum (Employee, I am an employee of Optum. Optum was paid by GSK for this work. My employment at Optum is not contingent upon this work.) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator) Ami R. Buikema, MPH, Optum (Employee, I am an employee of Optum. Optum was paid by GSK for this work. My employment at Optum is not contingent upon this work.) Tim Bancroft, PhD, Optum (Employee, I am an employee of Optum. Optum was paid by GSK for this work. My employment at Optum is not contingent upon this work.) Krista Schladweiler, PhD, Optum (Employee, I am an employee of Optum. Optum was paid by GSK for this work. My employment at Optum is not contingent upon this work.) Eleena Koep, MS, Optum (Employee) Patricia Novy, PhD, GSK (Employee, Shareholder) Cosmina Hogea, PhD, GlaxoSmithKline (Employee, Shareholder)

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1082. Characterization of Ceftriaxone-Resistant Viridans Streptococci Bacteremia Among Patients at a Comprehensive Cancer Center

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1268 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S570-S570

Author(s):

Paula Marsland ◽

Rupali Jain ◽

Frank Tverdek ◽

Paul Hendrie ◽

Catherine Liu ◽

...

Keyword(s):

Research Study ◽

Susceptibility Testing ◽

Hematologic Malignancy ◽

Scientific Research ◽

Comprehensive Cancer Center ◽

Cancer Center ◽

Cell Transplant ◽

Viridans Streptococci ◽

Study Investigator ◽

Definitive Therapy

Abstract Background Viridans streptococci (VS) are opportunistic oral commensals and a common cause of bacteremia, particularly in neutropenic patients. We sought to investigate the prevalence of ceftriaxone (CTX) resistance in VS blood isolates at our medical center among patients with cancer or treated with hematopoietic cell transplant (HCT), and to describe treatment and clinical course. Methods In this retrospective single center cohort study, we identified CTX-resistant (CTX-R) VS isolates among patients between January 2005 – June 2020. VS in blood cultures were identified using a combination of biochemicals and mass spectrometry. Susceptibility testing was performed by Kirby Bauer and E-Test. Demographic data, clinical outcomes, and antimicrobial use, including prophylactic, empiric treatment and definitive therapy choices were assessed through electronic medical record review. Results Of unique VS with sensitivities (n=693), 27 (3.9%) patients had confirmed CTX-R VS bacteremia over the 15-year period; the majority were S. mitis (23/27 [85%]). 17 (63%) were cancer center patients, of whom 15/17 (88%) had a known hematologic malignancy, 11 (65%) had undergone HCT, and 15 (88%) were neutropenic (absolute neutrophil count ≤500 cells/microliter). Of CTX-R strains, 15/17 (88%) had concomitant resistance to penicillin, erythromycin (12 [71%]), and levofloxacin (12 [71%]); all were sensitive to vancomycin. Most were on levofloxacin prophylaxis (11/17 [65%]) at the time of diagnosis. Initial empiric antibiotic choices primarily included cefepime, ceftazidime, or meropenem, with 16/17 (94%) receiving concomitant empiric vancomycin; 14/17 (82%) were de-escalated to vancomycin once sensitivities were obtained. 2/17 (12%) patients died within 30 days of CTX-R VS bacteremia. Despite increasing susceptibility testing among VS isolates, there did not appear to be an increase in the percentage of CTX-R over time. Conclusion VS is a common pathogen in neutropenic cancer patients treated with chemo and/or BMT, and multi-drug resistant CTX-R strains are of concern. In the modern era of ambulatory cancer care, prescribers must be cautious using ceftriaxone monotherapy in the absence of susceptibility information, particularly among patients with hematologic malignancies. Disclosures Steven A. Pergam, MD, MPH, Chimerix, Inc (Scientific Research Study Investigator)Global Life Technologies, Inc. (Research Grant or Support)Merck & Co. (Scientific Research Study Investigator)Sanofi-Aventis (Other Financial or Material Support, Participate in clinical trial sponsored by NIAID (U01-AI132004); vaccines for this trial are provided by Sanofi-Aventis)

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595. Letermovir (LTV) for Secondary Cytomegalovirus (CMV) Prevention in High Risk Hematopoietic Cell Transplant (HCT) Recipients: Interim Results of a Single Center, Open Label Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.793 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S401-S401

Author(s):

Gyuri Han ◽

Anat Stern ◽

Yiqi Su ◽

Boglarka Gyurkocza ◽

Craig Sauter ◽

...

Keyword(s):

High Risk ◽

Research Study ◽

Scientific Research ◽

Cell Transplant ◽

Research Support ◽

Open Label ◽

Material Support ◽

Study Investigator ◽

Research Grant

Abstract Background Letermovir (LTV) is effective for prevention (ppx) of primary clinically significant CMV infection (csCMVi) in the first 100 days after hematopoietic cell transplant (HCT). Data on LTV for secondary ppx is limited. We report on the efficacy and safety of LTV administered for 14 weeks as secondary CMV ppx. Methods Patients (pts) enrolled in an open label study of LTV (ClinicalTrials.gov identifier: NCT04017962) from August 2019 through February 2021 were analyzed. Key eligibility criteria were: CMV high risk (receipt of mismatched and/or T-cell depleted HCT and/or graft versus host disease (GVHD) requiring systemic immunosuppressants) AND prior csCMVi with either undetectable CMV (≤ 136 IU/mL) or ≥ 2 consecutive values < 300 IU/mL at enrollment. Pts with breakthrough csCMVi on LTV or history of LTV resistance were excluded. LTV was administered for 14 weeks or csCMVi whichever occurred first. The study duration was 24 weeks. CMV was monitored per standards of care. The primary endpoint was csCMVi by week 14. Secondary endpoints were csCMVi by week 24, LTV resistance, CMV end-organ disease (EOD) and adverse events (AE) at least possibly related to LTV. Results Of 20 pts analyzed, the median age was 58 years (interquartile range [IQR] 46-63); 17 (85%) pts were CMV seropositive, 7 (35%) received mismatched HCT (haploidentical 3, cord blood 3; mismatched unrelated 1), 9 (45%) received CD34 selected allograft and 9 (45%) had GVHD at enrollment. Fourteen (70%) pts had received prior LTV. The median time from HCT to enrollment was 156 (IQR 37-244) and 55 (IQR 40-69) days for pts with and without prior LTV, respectively (P=0.16). CMV at enrollment was < 136IU/mL for 8 (40%) pts. By week 14, 4 (20%) pts developed csCMVi at median 48 days (range 40-66). Resistance testing performed in 3 of the 4 pts, identified LTV resistance mutations in 2 pts. There were no AEs related to LTV, and none developed EOD. Two pts developed csCMVi in the follow up phase. Three pts died during follow up (due to relapse, treatment related toxicity and GVHD), and four pts are in follow up. Conclusion LTV secondary prophylaxis was safe and prevented recurrent csCMVi in 80% of high risk patients, including patients with prior LTV exposure. Our data supports the utility of LTV for secondary CMV prevention following HCT. Disclosures Boglarka Gyurkocza, MD, Actinium Pharma, Inc. (Grant/Research Support, Research Grant or Support) Genovefa Papanicolaou, MD, ADMA biologics and Siemens Healthineers (Consultant, Other Financial or Material Support)AlloVir (Consultant, Other Financial or Material Support)Amplyx (Scientific Research Study Investigator, Other Financial or Material Support)Astellas (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support, Other Financial or Material Support)Behring (Consultant, Other Financial or Material Support)Chimerix (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support, Other Financial or Material Support)Cidara (Consultant, Other Financial or Material Support)Merck & Co (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support, Other Financial or Material Support)Partners Therapeutics (Consultant, Other Financial or Material Support)Shionogi (Consultant, Other Financial or Material Support)Shire/Takeda (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support, Other Financial or Material Support) Genovefa Papanicolaou, MD, allovir (Individual(s) Involved: Self): Consultant; amplyx (Individual(s) Involved: Self): Consultant; behring (Individual(s) Involved: Self): Consultant; Merck&Co (Individual(s) Involved: Self): Consultant, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas, Research Grant or Support; octapharma (Individual(s) Involved: Self): Consultant; Partners Therapeutics (Individual(s) Involved: Self): Consultant; takeda (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator

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546. Therapeutic Effect of Regdanvimab in Patients with Mild to Moderate COVID-19: Day 28 Results from a Multicentre, Randomised, Controlled Pivotal Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.745 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S375-S375

Author(s):

Michael G Ison ◽

Jin Yong Kim ◽

Oana Sandulescu ◽

Liliana-Lucia Preotescu ◽

Norma Erendira Rivera Martinez ◽

...

Keyword(s):

High Risk ◽

Adverse Events ◽

Oxygen Therapy ◽

Research Study ◽

Scientific Research ◽

Supplemental Oxygen ◽

Phase 2 ◽

Study Investigator ◽

Supplemental Oxygen Therapy ◽

Research Grant

Abstract Background Regdanvimab is a monoclonal antibody with activity against SARS-CoV-2. A Phase 2/3 study with two parts is currently ongoing and data up to Day 28 of Part 1 is available while the data from 1315 patients enrolled in Part 2 are expected in June 2021. Methods This phase 2/3, randomized, parallel-group, placebo-controlled, double-blind study with 2 parts is aimed to assess the therapeutic efficacy of regdanvimab in outpatients with mild to moderate COVID-19, not requiring supplemental oxygen therapy. Patients aged >18 with the onset of symptoms within 7 days were eligible to be enrolled. Results In Part 1, 307 patients (101, 103, and 103 patients in the regdanvimab 40 mg/kg, regdanvimab 80 mg/kg, and placebo groups, respectively) were confirmed to have COIVD-19 by RT-qPCR at Day 1 (or Day 2). Regdanvimab significantly reduced the proportion of patients who required hospitalization or supplemental oxygen therapy compared to placebo (8.7% in the placebo vs. 4.0% in the regdanvimab 40 mg/kg). The difference in events rate was even larger in patients who met the high-risk criteria and confirmed a 66.1% reduction in patients receiving regdanvimab 40 mg/kg (Table 1). The median time to clinical recovery was shortened by 2.9 days (7.18 days for regdanvimab 40 mg/kg and 10.03 days for placebo; high-risk). Also, greater reductions from baseline viral load were shown in regdanvimab groups (Figure 1). The safety results confirmed that the regdanvimab was safe and well-tolerated. Occurrence of adverse events (Table 2) and results of other safety assessments were generally comparable among the 3 groups. The overall rate of infusion-related reaction was low and no serious adverse events or deaths were reported. The anti-drug antibody positive rate was low in the regdanvimab groups (1.4% in regdanvimab vs. 4.5% in placebo), and no antibody-dependent enhancement was reported. Conclusion Results from the first part of the study indicate that regdanvimab may lower the rate of hospitalisation or requirement of oxygen supplementation, with the greatest benefit noted in patients at high-risk of progressing to severe COVID-19. The second part of the study remains ongoing and blinded. Therefore, results for the primary endpoint are forthcoming and will be presented at IDWeek. Disclosures Michael G. Ison, MD, MS, Celltrion, Inc. (Consultant) Jin Yong Kim, MD, MPH, Celltrion, Inc. (Scientific Research Study Investigator) Oana Sandulescu, MD, PhD, Algernon Pharmaceuticals (Scientific Research Study Investigator)Atea Pharmaceuticals (Scientific Research Study Investigator)Celltrion, Inc. (Scientific Research Study Investigator)Diffusion Pharmaceuticals (Scientific Research Study Investigator)Regeneron Pharmaceuticals (Scientific Research Study Investigator) Liliana-Lucia Preotescu, MD, PhD, Celltrion, Inc. (Scientific Research Study Investigator) Norma Erendira Rivera Martinez, MD, Celltrion, Inc. (Scientific Research Study Investigator) Marta Dobryanska, MD, Celltrion, Inc. (Scientific Research Study Investigator) Victoria Birlutiu, Assoc. Prof. M.D. Ph.D., Celltrion, Inc. (Scientific Research Study Investigator)Lucian Blaga University of Sibiu, Romania & Hasso Plattner Foundation (Research Grant or Support) Egidia Gabriela Miftode, MD, PhD, Celltrion, Inc. (Scientific Research Study Investigator) Natalia Gaibu, MD, Celltrion, Inc. (Scientific Research Study Investigator) Olga Adriana Caliman-Sturdza, MD, PhD, Celltrion, Inc. (Scientific Research Study Investigator)Stefan cel Mare University of Suceava, Romania (Research Grant or Support) Simin-Aysel Florescu, MD, PhD, Celltrion, Inc. (Scientific Research Study Investigator) Anca Streinu-Cercel, MD, PhD, Assoc.Prof. Infectious diseases, Algernon Pharmaceuticals (Scientific Research Study Investigator)Atea Pharmaceuticals (Scientific Research Study Investigator)Celltrion, Inc. (Scientific Research Study Investigator)Diffusion Pharmaceuticals (Scientific Research Study Investigator)Regeneron Pharmaceuticals (Scientific Research Study Investigator) Sang Joon Lee, n/a, Celltrion, Inc. (Employee) Sung Hyun Kim, n/a, Celltrion, Inc. (Employee) Il Sung Chang, n/a, Celltrion, Inc. (Employee) Yun Ju Bae, n/a, Celltrion, Inc. (Employee) Jee Hye Suh, n/a, Celltrion, Inc. (Employee) Mi Rim Kim, n/a, Celltrion, Inc. (Employee) Da Re Chung, n/a, Celltrion, Inc. (Employee) Sun Jung Kim, n/a, Celltrion, Inc. (Employee) Seul Gi Lee, n/a, Celltrion, Inc. (Employee) Ga Hee Park, n/a, Celltrion, Inc. (Employee) Joong Sik Eom, MD, PhD, Celltrion, Inc. (Consultant)

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