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

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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1393. Factors Associated with Co-administration of Pentavalent DTaP-IPV/Hib and Monovalent Hepatitis B Vaccine in the United States (US)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1575 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S706-S706

Author(s):

Tanaz Petigara ◽

Ya-Ting Chen ◽

Zhiwen Liu ◽

Michelle Goveia ◽

David Johnson ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

The United States ◽

Vaccination Schedule ◽

Provider Type ◽

Factors Associated ◽

Study Investigator ◽

Region Of Residence ◽

Birth Dose ◽

To Receive

Abstract Background The US vaccination schedule includes DTaP, IPV, Hib and HepB doses in the first 6 months of life. A previous analysis found variability in the timing of HepB doses in infants receiving DTaP-IPV/Hib. We explored factors associated with co-administration of DTaP-IPV/Hib and HepB on the same day. Methods This was a retrospective study using the MarketScan® commercial claims and encounters database. Infants born from 1 July 2010 - 30 June 2016, continuously enrolled in an insurance plan for ≥ 13 months and receiving ≥ 3 DTaP-IPV/Hib doses were included. Infants were assessed for HepB claims relative to the first and third DTaP-IPV/Hib doses. Because a HepB birth dose was assumed, the first HepB claim from 29 - 169 days following birth was counted as Dose 2, and the second claim from 170 days - 12 months as Dose 3. Associations between demographic, provider, and insurance characteristics, receipt of other pediatric vaccines, and co-administration of DTaP-IPV/Hib and HepB were analyzed using multivariate logistic regression. Results Among 165,553 infants who received a first DTaP-IPV/Hib dose, 60.7% received HepB Dose 2 on the same day. Among 162,217 infants who received a third DTaP-IPV/Hib dose, 45.1% received HepB Dose 3 on the same day. Infants in the Northeast were less likely (OR=0.38, 95%CI=0.36-0.39), while those in the West were more likely (OR=1.41, 95%CI=1.36-1.46) than infants in the South to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day. Infants vaccinated by pediatricians (OR=0.54, 95%CI=0.53-0.55) were less likely to receive the first dose of DTaP-IPV/Hib and HepB Dose 2 on the same day compared to infants vaccinated by family physicians. Infants who received PCV on the same day as the first dose of DTaP-IPV/Hib were more likely to receive HepB Dose 2 (OR=6.96, 95%CI=6.30-7.70) that day. These factors were also associated with co-administration of the third dose of DTaP-IPV/Hib and HepB Dose 3. Conclusion Differences in co-administration of DTaP-IPV/Hib and HepB were associated with region of residence, provider type and co-administration of PCV. The reasons underlying these differences merit exploration. A hexavalent vaccine containing DTaP, IPV, Hib, and HepB could improve timeliness of HepB vaccination, while reducing the number of injections during infancy. Disclosures Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Zhiwen Liu, PhD, Merck & Co., Inc., (Employee) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) 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)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1686 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S755-S756

Author(s):

Woody Sorey ◽

Elizabeth M Krantz ◽

Jessica Morris ◽

John Klaassen ◽

Ania Sweet ◽

...

Keyword(s):

High Risk ◽

Cancer Patients ◽

Symptom Onset ◽

Research Study ◽

Scientific Research ◽

Clinical Encounter ◽

Cancer Center ◽

Influenza B ◽

Antibiotic Prescribing ◽

Study Investigator

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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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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835. Improvement in Diet Attenuates Antiretroviral Therapy (ART) Associated Weight Gain in Persons with Human Immunodeficiency Virus (PWH)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1031 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S509-S510

Author(s):

Yesha Patel ◽

Anjali Doshi ◽

Anna Levesque ◽

Shelsie Lindor ◽

Robert Moranville ◽

...

Keyword(s):

Weight Gain ◽

Combination Therapy ◽

Weight Change ◽

Regression Models ◽

Research Study ◽

Scientific Research ◽

Secondary Outcome ◽

Factors Associated ◽

Study Investigator

Abstract Background Weight gain among PWH on ART is a growing clinical concern. We explore factors associated with weight gain at The Ohio State University Wexner Medical Center Infectious Diseases Clinic. Methods This was a single-center, retrospective, cohort study of adult PWH on ART for at least 3 months seen at our clinic from 1/1/2015 to 1/1/2019. Patients with CD4+ T cell count < 200 cells/mm3, viral load >200 copies/mL, history of malignancy, or pregnancy were excluded. 870 patients met criteria. Patient demographics, lifestyle factors, medical co-morbidities, concurrent medications, and ART regimens were documented during the study period. The primary outcome was percent weight change over the follow up period. Secondary outcome was the odds of > 5kg weight gain over the study period. The effects of concurrent medications, medical comorbidities, ART combinations, and self-reported lifestyle behaviors on these outcomes were modeled using mixed effect linear and logistic regression analysis. Results At baseline, 83.6% were male, 29.2% were African American, and 65.6% had a body mass index ≥ 25 kg/m. Over a mean follow up of 1.86 years, the study population gained a mean percent weight of 2.12 ± 0.21% (p< 0.001) with an odds of weight gain >5kg of 0.293 (p< 0.001). Male sex and increasing age were significantly associated with a decrease in percent weight over the study period as reflected in the table below. Diet was also significantly associated with a decrease in percent weight change over the study period of -1.99 ± 0.47 %, p= < 0.001 and a lower odds of > 5kg of weight gain (OR= 0.70, 95% CI= 0.50 – 0.97, p=0.03). In regression models, combination therapy with tenofovir alafenamide (TAF) and integrase strand transfer inhibitor (INSTI) containing regimens were significantly associated with an increase in percent weight over the study period. Other significant factors including demographics and ART regimens are noted in Table 1. Table 1. Multivariable Regression Models* Conclusion Weight gain in PWH is multifactorial. Key factors associated with weight gain include combination therapy with TAF, particularly when combined with an INSTI. This data highlights the influential role of diet in PWH at risk of ART-associated weight gain. Disclosures Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)

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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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1157. Clinical Safety, Efficacy, and Pharmacokinetics of Fosmanogepix, a Novel First-in-class Antifungal, in Patients with Renal Insufficiency: Subset Analysis from a Phase 2 Candidemia Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1343 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S605-S605

Author(s):

Pierre Bulpa ◽

Galia Rahav ◽

Ilana Oren ◽

Mickaël Aoun ◽

George R Thompson ◽

...

Keyword(s):

Renal Function ◽

Renal Insufficiency ◽

Antifungal Agents ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Antifungal Treatment ◽

Successful Outcome ◽

Review Panel ◽

Study Investigator

Abstract Background Fosmanogepix (FMGX) is a first-in-class antifungal agent, with a unique MOA targeting the fungal enzyme Gwt1, and broad-spectrum activity against yeasts and molds, including fungi resistant to other antifungal agents. Patients with candidemia often have underlying renal insufficiency or are receiving medications that affect renal function. This analysis evaluated outcomes in patients with varying degrees of renal insufficiency. Methods This global, multicenter, open-label, non-comparative study evaluated the safety and efficacy of FMGX for first-line treatment of candidemia. Patients with a recent diagnosis of candidemia defined as positive blood culture for Candida spp within 96 hrs prior to study entry with ≤ 2 days of prior antifungal treatment were eligible, including those with renal insufficiency. Patients with neutropenia, C. krusei infection, deep-seated Candida infections or receiving hemodialysis were excluded. Subjects were treated with FMGX for up to 14 days: 1000 mg IV BID for 1 day, then 600 mg IV QD for at least 2 days, followed by either 600 mg IV QD or 700 mg PO QD. Patients requiring antifungal treatment beyond 14 days received fluconazole. The primary efficacy endpoint was outcome at end of study treatment (EOST) as determined by an independent data review committee. Successful outcome was defined as survival with clearance of Candida from blood cultures with no additional antifungal treatment. Results 14/21 (66%) subjects had some degree of renal insufficiency: 7 had mild renal insufficiency (GFR:60-89), 5 had moderate renal insufficiency (GFR:30-59), and 2 had severe renal insufficiency (GFR:15-29). 12/14 (86%) completed study treatment, and treatment was successful at EOST in 12/14 (86%) subjects. Decline in renal function was not observed at EOST. 4 had worsening of renal function during the follow-up period; none required dialysis. Renal impairment did not increase exposure of FMGX. There were no treatment-related adverse events. Conclusion FMGX demonstrated high level treatment success with no evidence of drug-related nephrotoxicity, with no dose adjustments required. These preliminary data support the continued evaluation of FMGX in patients with candidemia and renal dysfunction as an alternative to potentially nephrotoxic antifungal agents. Disclosures Pierre Bulpa, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Galia Rahav, MD, AstraZeneca (Scientific Research Study Investigator) Mickaël Aoun, MD, Amplyx Pharmaceuticals (Scientific Research Study Investigator) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Bart Jan Kullberg, MD, FRCP, FIDSA, Amplyx (Advisor or Review Panel member) Sara Barbat, BSN, RN, Amplyx Pharmaceuticals (Employee) Pamela Wedel, BSc, Amplyx Pharmaceuticals (Employee) Haran T. Schlamm, MD, Amplyx (Consultant) Michael Hodges, BSc. MD, Amplyx Pharmaceuticals Inc. (Employee)

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1608. Efficacy of Ceftolozane/Tazobactam for Multidrug-Resistant Gram-Negative Infections in Multiple Urban Hospitals

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1788 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S798-S799

Author(s):

Nicolo Cabrera ◽

Truc T Tran ◽

Travis J Carlson ◽

Faris Alnezary ◽

William R Miller ◽

...

Keyword(s):

Research Study ◽

Clinical Success ◽

Significant Proportion ◽

Scientific Research ◽

Panel Member ◽

Multidrug Resistant ◽

Outcome Data ◽

Research Support ◽

Gram Negative ◽

Study Investigator

Abstract Background Ceftolozane/tazobactam (C/T) is a novel cephalosporin/beta-lactamase inhibitor combination developed for use against multidrug-resistant (MDR) Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T is approved for complicated urinary tract and intraabdominal infections as well as hospital-acquired/ventilator-associated bacterial pneumonias. However, comprehensive clinical characterization of patients treated with C/T in non-FDA-approved indications is limited. Methods Patients ≥18 years who received C/T for ≥48 hours while hospitalized in 9 acute care centers in Houston, TX from January 2016 through September 2018 were included. Demographic, microbiologic, treatment and clinical outcome data were retrospectively collected by chart review. In patients who received multiple inpatient courses of C/T, only the first course with C/T was assessed. Results 210 patients met inclusion criteria: 58% were non-white, 35% were female and 13% were immunocompromised. Median age was 61 years (IQR, 48 to 69). Median Charlson comorbidity index was 5 (IQR, 2 to 6). At the onset of the index episode, a significant proportion of patients required intensive care unit admission (44%), mechanical ventilation (37%) and pressor support (22%). Respiratory sources were the most common (50%) followed by urine (15%). Positive cultures were documented in 93% of the cases and PA was found in 86%. Majority (95%) of PA which were MDR. C/T use was guided by susceptibility testing of the index isolate in ca. 52%. In 5.7% of cases, C/T was used to escalate therapy without any documented C/T-susceptible organism. Half (51%) of the cohort received initial dosing appropriate for renal function while 36% receiving a lower than recommended dose. Clinical success (i.e., recovery from infection-related signs and symptoms) occured in 77%. The in-hospital mortality rate in our cohort was 15% with 26 of 31 deaths deemed infection-related. Conclusion We report a large multicenter observational cohort that received C/T. A 77% clinical success with the use of C/T was documented. These data support the use of C/T in critically ill patients infected with MDR PA. Disclosures William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Laura A. Puzniak, PhD, Merck (Employee) 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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