673. Updated CLSI Ciprofloxacin Breakpoints from a Multicenter Assessment for Enterobacterales, Salmonella spp. and Pseudomonas aeruginosa Using MicroScan Dried Gram Negative MIC Panels

Abstract Background Updated US FDA/CLSI ciprofloxacin breakpoints were evaluated against data from a multicenter clinical study with Enterobacterales, Salmonella spp. and P. aeruginosa on a MicroScan Dried Gram-negative MIC (MSDGN) Panel. MIC results were compared to results obtained with frozen broth microdilution panels prepared according to CLSI methodology. Methods MSDGN panels were evaluated at three clinical sites by comparing MIC values obtained using the MSDGN panels to MICs utilizing a CLSI broth microdilution reference panel. Data from the combined phases of efficacy and challenge included 803 Enterobacterales, Salmonella spp. and P. aeruginosa clinical isolates tested using the turbidity and Prompt® methods of inoculation. To demonstrate reproducibility, a subset of 12 organisms were tested on MSDGN panels at each site during reproducibility. MSDGN panels were incubated at 35 ± 1ºC and read on the WalkAway System, the autoSCAN-4 instrument, and visually. Read times for the MSDGN panels were at 16-20 hours. Frozen reference panels were prepared and read according to CLSI methodology. FDA and CLSI breakpoints (µg/mL) used for interpretation of MIC results were: Enterobacterales ≤ 0.25 S, 0.5 I, ≥ 1 R; Salmonella spp. ≤ 0.06 S, 0.12-0.5 I, ≥ 1 R; P. aeruginosa ≤ 0.5 S, 1 I, ≥ 2 R. Results Essential and categorical agreement was calculated compared to frozen reference panel results. Results for isolates tested during efficacy and challenge with Prompt inoculation and manual read are as follows: Conclusion Ciprofloxacin MIC results for Enterobacterales, Salmonella spp., and P. aeruginosa obtained with the MSDGN panel correlate well with MICs obtained using frozen reference panels using updated FDA/CLSI interpretive criteria in this multicenter study. * PROMPT® is a registered trademark of 3M Company, St. Paul, MN USA. BEC, the stylized logo and the BEC product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the US and other countries. Disclosures Maria M. Traczewski, BS MT (ASCP), Beckman Coulter (Scientific Research Study Investigator) Denise Beasley, BS, Beckman Coulter (Other Financial or Material Support, Research personnel) Amanda Harrington, PhD, Beckman Coulter (Scientific Research Study Investigator) Sharon DesJarlais, BS, Beckman Coulter (Other Financial or Material Support, Research personnel) Omai Garner, PhD, D(ABMM), Beckman Coulter (Scientific Research Study Investigator) Christine Hastey, PhD, Beckman Coulter (Employee) Regina Brookman, BS, Beckman Coulter (Employee) Zabrina Lockett, MS, Beckman Coulter (Employee) Jennifer Chau, PhD, Beckman Coulter (Employee)

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667. Multicenter Assessment of Enterobacterales, Salmonella spp. and Pseudomonas aeruginosa Using Updated CLSI Levofloxacin Breakpoints on MicroScan Dried Gram Negative MIC Panels

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.860 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S388-S389

Author(s):

Omai Garner ◽

Maria M Traczewski ◽

Denise Beasley ◽

Amanda Harrington ◽

Sharon DesJarlais ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Reference Panel ◽

Broth Microdilution ◽

Salmonella Spp ◽

Research Personnel ◽

Gram Negative ◽

Material Support ◽

Study Investigator ◽

Support Research

Abstract Background Data from a multicenter clinical study with Enterobacterales, Salmonella spp. and P. aeruginosa on a MicroScan Dried Gram-negative MIC (MSDGN) Panel was evaluated with updated US FDA/CLSI levofloxacin breakpoints. MIC results were compared to results obtained with frozen broth microdilution panels prepared according to CLSI methodology. Methods A total of 839 Enterobacterales, Salmonella spp. and P. aeruginosa clinical isolates were tested at three clinical sites in efficacy and challenge combined. MSDGN panels were evaluated with turbidity and Prompt® methods of inoculation. MIC values obtained from the MSDGN panels were compared to MICs utilizing a CLSI broth microdilution reference panel. To assess reproducibility, a subset of 15 organisms were tested on MSDGN panels at each site. MSDGN panels were incubated at 35 ± 1ºC and read on the WalkAway System, the autoSCAN-4 instrument, and visually. Read times for the MSDGN panels were at 16-20 hours. Frozen reference panels were prepared and read according to CLSI methodology. FDA and CLSI breakpoints (µg/mL) used for interpretation of MIC results were: Enterobacterales ≤ 0. 5 S, 1 I, ≥ 2 R; Salmonella spp. ≤ 0.12 S, 0.25-1 I, ≥ 2 R; P. aeruginosa ≤ 1 S, 2 I, ≥ 4 R. Results Essential and categorical agreement were calculated compared to frozen reference panel results. Results for isolates tested during efficacy and challenge with Prompt inoculation and manual read are as follows: Conclusion Levofloxacin MIC results for Enterobacterales, Salmonella spp., and P. aeruginosa obtained with the MSDGN panel correlate well with MICs obtained using frozen reference panels using updated FDA/CLSI interpretive criteria in this multicenter study. * PROMPT® is a registered trademark of 3M Company, St. Paul, MN USA. BEC, the stylized logo and the BEC product and service marks mentioned herein are trademarks or registered trademarks of Beckman Coulter, Inc. in the US and other countries. Disclosures Omai Garner, PhD, D(ABMM), Beckman Coulter (Scientific Research Study Investigator) Maria M. Traczewski, BS MT (ASCP), Beckman Coulter (Scientific Research Study Investigator) Denise Beasley, BS, Beckman Coulter (Other Financial or Material Support, Research personnel) Amanda Harrington, PhD, Beckman Coulter (Scientific Research Study Investigator) Sharon DesJarlais, BS, Beckman Coulter (Other Financial or Material Support, Research personnel) Christine Hastey, PhD, Beckman Coulter (Employee) Regina Brookman, BS, Beckman Coulter (Employee) Zabrina Lockett, MS, Beckman Coulter (Employee) Jennifer Chau, PhD, Beckman Coulter (Employee)

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354. SARS-CoV-2 Viral Viability Culture and Sequencing from Immunocompromised Patients with Persistently Positive SARS-CoV-2 PCR Results

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.555 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S281-S281

Author(s):

Abby Sung ◽

Adam Bailey ◽

Meghan Wallace ◽

Henry B Stewart ◽

David McDonald ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Study Investigator ◽

Jewish Hospital ◽

Support Research ◽

Research Grant

Abstract Background Immunocompromised (IC) patients (pts) can have prolonged SARS-CoV-2 PCR positivity, even after resolution of COVID-19 symptoms. This study aimed to determine if viable virus could be detected in samples collected > 21 days after an initial positive (pos) SARS-CoV-2 PCR in IC pts. Methods We obtained 20 remnant SARS-CoV-2 PCR pos nasopharyngeal swabs from IC pts (bone marrow or solid organ transplant, high dose steroids, immunosuppressive medications) with a pos repeat PCR within the previous 30 days. The repeat specimens were cultured on Vero-hACE2-TMPRSS2 cells and incubated for 96 hours to assess viral viability. Viable RNA and infectious virus in the cultured cells were measured by qPCR and infectious plaque assays. RNA sequencing was performed on a HiSeq platform (Illumina). Samples also underwent SARS-CoV-2 antigen (Ag) testing (BD Veritor). Clinical data were extracted from the electronic health record by chart review. Results Pt characteristics are in Table 1. Viral cultures from the repeat specimen were negative (neg) for 18 pts and pos for 2 (Table 2). Pt 1 is a 60M treated with obinatuzumab 19 days prior to his first pos PCR test, with repeat specimen collected 21 days later (cycle threshold (Ct) not available). Pt 1 had a low viral titer (27 PFU/mL) & a D614G mutation on sequencing. Pt 2 is a 75M treated with rituximab 10 days prior to his first pos PCR test, with repeat specimen collected 23 days later (Ct 27.56/27.74). Pt 2 had a high viral titer (2e6 PFU/mL) and D614G, S98F, and S813I mutations. Demographics of Study Population (N=20) Characteristics of patients with a positive SARS-CoV-2 viral culture Conclusion 90% of specimens collected > 21 days after an initial pos SARS-CoV-2 PCR did not have viable virus detected on their repeat specimen. The 2 pts with pos viral cultures had active hematologic malignancies treated with an anti-CD20 mAb at the time of COVID-19 diagnosis. One pt had a high concentration of active, viable virus. No known variants of concern were noted in this cohort, collected in Q2 2020, though prolonged replication is a risk for variant development. Further data are needed about risk factors for persistent viable viral shedding & methods to prevent transmission of viable virus from IC hosts. Disclosures Victoria J. Fraser, MD, CDC Epicenters (Grant/Research Support)Cigna/Express Scripts (Other Financial or Material Support, Spouse is Chief Clinical Officer)Doris Duke Fund to Retain Clinical Scientists (Grant/Research Support, Research Grant or Support)Foundation for Barnes-Jewish Hospital (Grant/Research Support, Research Grant or Support)NIH (Grant/Research Support, Research Grant or Support) Victoria J. Fraser, MD, Centers for Disease Control and Prevention (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; Cigna/Express Scripts (Individual(s) Involved: Spouse/Partner): Employee; Doris Duke Charitable Foundation (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; National Institutes of Health (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support; The Foundation for Barnes-Jewish Hospital (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Michael S. Diamond, MD, PhD, Carnival Corporation (Consultant)Emergent BioSolutions (Grant/Research Support)Fortress Biotech (Consultant)Immunome (Advisor or Review Panel member)Inbios (Consultant)Moderna (Grant/Research Support, Advisor or Review Panel member)Vir Biotechnology (Consultant, Grant/Research Support) Carey-Ann Burnham, PhD, BioFire (Grant/Research Support, Other Financial or Material Support)bioMerieux (Grant/Research Support)Cepheid (Consultant, Grant/Research Support)Luminex (Grant/Research Support)Roche (Other Financial or Material Support) Carey-Ann Burnham, PhD, BioFire (Individual(s) Involved: Self): Grant/Research Support; bioMerieux (Individual(s) Involved: Self): Grant/Research Support, Scientific Research Study Investigator, Speakers’ bureau; Cepheid (Individual(s) Involved: Self): Consultant, Grant/Research Support, Scientific Research Study Investigator; Luminex (Individual(s) Involved: Self): Scientific Research Study Investigator Hilary Babcock, MD, MPH, FIDSA, FSHEA, Nothing to disclose

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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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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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548. Convalescent Plasma in Hospitalized Pediatric and Obstetric patients with COVID-19

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.747 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S376-S376

Author(s):

Saki Ikeda ◽

Eduardo Benzi ◽

Lisa Hensch ◽

Sridevi Devaraj ◽

Shiu-Ki Rocky Hui ◽

...

Keyword(s):

Pediatric Patients ◽

Research Study ◽

High Titer ◽

Serum Antibody ◽

Laboratory Data ◽

Scientific Research ◽

Published Data ◽

Material Support ◽

Study Investigator ◽

Antibody Levels

Abstract Background Published data on COVID-19 convalescent plasma (CCP) use in children and obstetric patients is limited. We describe a single-center experience of hospitalized patients who received CCP for acute COVID-19. Methods We performed a retrospective review of children 0-18-years-old and pregnant patients hospitalized with laboratory-confirmed acute COVID-19 who received CCP from March 1st, 2020 to March 1st, 2021. Clinical and laboratory data were collected to assess the safety of CCP administration. Antibodies to SARS-CoV-2 were measured before and at various timepoints post CCP transfusion. Correlation between SARS-CoV-2 immunoglobulin administered versus the SARS-CoV-2 anti-Spike immunoglobulin response in patient serum was assessed. Results Twenty-two children and 10 obstetric patients were eligible. 12 pediatric and 8 obstetric patients had moderate disease and 10 pediatric and 2 obstetric patients had severe disease. 5 pediatric patients died. 18/37 (48.6%) CCP units that were measured met FDA criteria for a high IgG titer. There were no complications with transfusion based on CDC, NHSN Biovigilance Component: Hemovigilance Module Surveillance Protocol. Two pediatric patients had fevers a few hours after CCP with low suspicion for a transfusion reaction. Median SARS-CoV-2 anti-spike antibody levels of pediatric patients post-transfusion for 0-7 days was 80.6AU/mL (range: 2-1070), 8-21 days was 180AU/mL (range: 12-661) and >21 days was 210AU/mL (range: 4.1-1220). For obstetric patients, post-transfusion antibody levels were only obtained 0-7 days post-transfusion with median 45AU/mL (range: 9.5-100). High-titer CCP showed a positive correlation with rise in patient immunoglobulin levels only in the obstetric patients but not in pediatric patients. Conclusion CCP was administered safely to our moderately to severely ill pediatric and obstetric patients. Among pediatric patients, the median serum antibody level increased over time after transfusion and suggested that CCP did not interfere with the endogenous antibody production. Antibody dose of high-titer CCP correlated with post-transfusion response in only obstetric patients. Randomized trials in pediatric and obstetric patients are needed to further understand how to dose CCP and evaluate efficacy. Disclosures Jun Teruya, MD, PhD, Apelo Consulting Pvt. Ltd (Consultant)Hemosonics (Other Financial or Material Support, Honorarium) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB)

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1178. Sustained Vaccine Effectiveness Against Influenza-Associated Hospitalization in Children: Evidence from the New Vaccine Surveillance Network, 2015-2016 Through 2019-2020

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1371 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S681-S682

Author(s):

Leila C Sahni ◽

Eric A Naioti ◽

Samantha M Olson ◽

Angela P Campbell ◽

Marian G Michaels ◽

...

Keyword(s):

Influenza Vaccine ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Onset Date ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Study Investigator ◽

Research Grant

Abstract Background Adult studies have demonstrated intra-season declines in influenza vaccine effectiveness (VE) with increasing time since vaccination; however, data in children are limited. Methods We conducted a prospective, test-negative study of children ages 6 months through 17 years hospitalized with acute respiratory illness at 7 pediatric medical centers each season in the New Vaccine Surveillance Network during the 2015-2016 through 2019-2020 influenza seasons. Cases were children with an influenza-positive molecular test; controls were influenza-negative children. Controls were matched to cases by illness onset date using 3:1 nearest neighbor matching. We estimated VE [100% x (1 – odds ratio)] by comparing the odds of receipt of ≥ 1 dose of influenza vaccine ≥ 14 days before the onset of illness that resulted in hospitalization among influenza-positive children to influenza-negative children. Changes in VE over time between vaccination date and illness onset date during each season were estimated using multivariable logistic regression models. Results Of 8,430 hospitalized children (4,781 [57%] male; median age 2.4 years), 4,653 (55%) received ≥ 1 dose of influenza vaccine. On average, 48% and 85% of children were vaccinated by the end of October and December, respectively. Influenza-positive cases (n=1,000; 12%) were less likely to be vaccinated than influenza-negative controls (39% vs. 61%, p< 0.001) and overall VE against hospitalization was 53% (95% CI: 46%, 60%). Pooling data across 5 seasons, the odds of any influenza-associated hospitalization increased 0.96% (95% CI: -0.76%, 2.71%) per week with a corresponding weekly decrease in VE of 0.45% (p=0.275). Odds of hospitalization with time since vaccination increased 0.66% (95% CI: -0.76%, 2.71%) per week in children ≤ 8 years (n=3,084) and 2.16% (95% CI: -1.68%, 6.15%) per week in children 9-17 years (n=771). No significant differences were observed by virus subtype or lineage. Figure 1. Declines in influenza VE over time from 2015-2016 through 2019-2020, overall (a) and by age group (b: ≤ 8 years; c: 9-17 years) Conclusion We observed minimal intra-season declines in VE against influenza-associated hospitalization in U.S. children. Vaccination following Advisory Committee on Immunization Practices guidelines and current timing of vaccine receipt is the best strategy for prevention of influenza-associated hospitalization in children. Disclosures Marian G. Michaels, MD, MPH, Viracor (Grant/Research Support, performs assay for research study no financial support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Elizabeth P. Schlaudecker, MD, MPH, Pfizer (Grant/Research Support)Sanofi Pasteur (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)Quidel (Grant/Research Support, Other Financial or Material Support, Donation of supplies/kits)Sanofi (Grant/Research Support, Other Financial or Material Support, HAI/NAI testing) Natasha B. Halasa, MD, MPH, Genentech (Individual(s) Involved: Self): I receive an honorarium for lectures - it’s a education grant, supported by genetech, Other Financial or Material Support, Other Financial or Material Support; Sanofi (Individual(s) Involved: Self): Grant/Research Support, Research Grant or Support Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant) Christopher J. Harrison, MD, GSK (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB)

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860. A Proposed Standard for Hospital Bioaerosol Monitoring in Avoiding Nosocomial Mould Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1049 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S469-S470

Author(s):

Garret T Seiler ◽

Luis Ostrosky-Zeichner ◽

Lance Ferguson ◽

Kelly Boston ◽

Mike Grant ◽

...

Keyword(s):

Research Study ◽

Fungal Infections ◽

Scientific Research ◽

Quality Standard ◽

Exposure Limits ◽

Material Support ◽

Study Investigator ◽

Airborne Contamination ◽

The Mean ◽

Particle Counts

Abstract Background Recent nosocomial outbreaks of mould infections have been linked to bioaerosols. Active and passive environmental sampling is a primary method of quantifying airborne contamination in the hospital, but currently there are no standardized Occupational Exposure Limits (OELs) for the avoidance of nosocomial infections. Methods Between March 2016 and December 2019, 186 post-construction/post-cleaning air samples were collected to measure particle counts based on defined size criteria Lighthouse handheld Particle Counter) and viable air fungal cultures (Anderson single stage N6 Viable Particulate Sampler) across wards of a 1,082 bed hospital in Houston, Texas, and compared with outdoor controls. Areas were cleared for occupancy if the ≤ 0.3micron particle counts were reduced by the expected efficacy of the HVAC unit and if indoor fungi airborne concentrations in CFU/m³ were also reduced or did not exceed the outdoor ambient reference levels for each separate day of site assessment. Results The mean counts of particles ≤ 0.3microns were as follows: floors 37,427.50 (-32% reduction), operating rooms 8,163.88 (95% reduction), OR sterile core 15,001.31 (89% reduction), ICU 7,640.15 (93% reduction), radiology suites 1,046.25 (97% reduction), and outpatient areas 17,891.58 (82% reduction). The table indicates the reported mean density (CFU/m³) data and species of fungi isolated in viable bioaerosol samples, 13 of which matched outdoor reference isolates. The mean density of outdoor cultures was 292.37 compared to all indoor units 24.53 (91.61% reduction), floors 25.44 (91.3% reduction), ICUs 28.19 (90.4% reduction), radiology suites 22.5 (92.3% reduction), and ORs 12.79 (95.6% reduction). During this time, no nosocomial fungal infections or outbreaks were documented for the institution. Table 1: Mean Density (cfu/mm3) of Fungal Species per Location Conclusion An indoor air quality standard comprised of particle count data reduced by the expected efficacy of the operating HVAC unit and also existing indoor viable fungi in units of CFU/m³ that did not exceed the outdoor reference could potentially be correlated with avoidance of nosocomial mould infections. Disclosures Luis Ostrosky-Zeichner, MD, Amplyx (Scientific Research Study Investigator)Astellas (Consultant, Scientific Research Study Investigator, Other Financial or Material Support, Non-branded educational speaking)Biotoscana (Consultant, Other Financial or Material Support, Non-branded educational speaking)Cidara (Consultant, Scientific Research Study Investigator)F2G (Consultant)Gilead (Consultant)Mayne (Consultant)Octapharma (Consultant)Pfizer (Other Financial or Material Support, Non-branded educational speaking)Scynexis (Consultant, Grant/Research Support, Scientific Research Study Investigator)Stendhal (Consultant)Viracor (Consultant)

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449. Performance of the Brighton Case Definition for Multisystem Inflammatory Syndrome in Children (MIS-C) Among a Large Single Center Cohort

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.648 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S325-S325

Author(s):

Jessica Nguyen ◽

Isabella Osuna ◽

Eyal Muscal ◽

Kristen Sexson ◽

Marietta DeGuzman ◽

...

Keyword(s):

Disease Activity ◽

Research Study ◽

Scientific Research ◽

Case Definition ◽

Additional Patient ◽

Single Center ◽

Material Support ◽

Study Investigator ◽

Definite Case ◽

Inflammatory Syndrome

Abstract Background Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, life-threatening, hyperinflammatory condition presumed to follow SARS-CoV-2 infection. Whether MIS-C can also follow SARS-CoV-2 vaccination is not clear, making MIS-C an adverse event of special interest following immunization. Monitoring for post-vaccine MIS-C is complicated by the clinical overlap of MIS-C with numerous other inflammatory conditions including Kawasaki Disease, toxic shock syndrome, and viral myocarditis. A case definition for MIS-C was recently created with the Brighton Collaboration (BC). We aimed to determine the performance of the BC MIS-C case definition among a large, single-center MIS-C cohort. Methods Retrospective review was performed for the first 100 MIS-C cases at our institution (May 2020-February 2021). All cases met the Centers for Disease Control and Prevention (CDC) case definition. Data on age, presentation, laboratory results and cardiac studies were collected and used to determine cases that fulfilled the BC case definition for MIS-C (see figure). Case Definition: Definite Case Results Of 100 children (age < 21 years) diagnosed with MIS-C using the CDC case definition, 93 patients also fulfilled the BC definition. All 100 patients had elevated laboratory markers of inflammation and positive SARS-CoV-2 antibodies. However, 1 patient was excluded for significant respiratory symptoms (pulmonary hemorrhage), 5 were excluded due to only 1 clinical feature, and an additional patient was excluded for having none of the measures of disease activity. Among the 93 patients fulfilling the revised case definition, 88 (95%) met criteria for a definite case. Five of the 93 patients (5%) were considered probable cases, 1 reported only 1 day of fever and 4 had only 1 measure of disease activity. Conclusion The original case definitions for MIS-C were created rapidly following the first emerging reports of this hyperinflammatory state. Knowledge of the varied clinical presentations of this disorder has grown substantially. Modification of the case definition to include features truly representative of MIS-C will allow for more precise diagnosis in the face of conditions which mimic MIS-C, and for accurate and reliable monitoring for adverse events following immunization. Disclosures Flor M. Munoz, MD, Biocryst (Scientific Research Study Investigator)Gilead (Scientific Research Study Investigator)Meissa (Other Financial or Material Support, DSMB)Moderna (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Pfizer (Scientific Research Study Investigator, Other Financial or Material Support, DSMB)Virometix (Other Financial or Material Support, DSMB)

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468. Delayed Mortality Among Solid Organ Transplant Recipients Hospitalized for Covid-19: An International Multicenter Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.667 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S336-S337

Author(s):

Madeleine R Heldman ◽

Olivia S Kates ◽

Robert M Rakita ◽

Erika D Lease ◽

Ajit P Limaye ◽

...

Keyword(s):

Risk Factors ◽

Research Study ◽

Organ Transplant ◽

Scientific Research ◽

Solid Organ Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Material Support ◽

Study Investigator ◽

Solid Organ Transplant Recipients

Abstract Background Studies of solid organ transplant recipients (SOTr) hospitalized for Covid-19 have focused on short-term outcomes with approximately 30 days of follow-up time. Intermediate-term mortality and associated risk factors for intermediate-term death have not previously been reported. Methods Using data from a multi-center registry, we assessed mortality by 90 days among SOTr hospitalized for Covid-19 between 3/1/2020 and 12/31/2020. Multivariable Cox-proportional hazard models were used to compare risk factors for mortality by 28 and 90 days. Covariates were selected a priori based on known predictors of death in SOTr hospitalized for Covid-19. All patients were followed for 90 days or were censored at the time of death or last clinical contact, if this occurred prior to day 90 after diagnosis. Results Among SOTr hospitalized for Covid-19, 198/979 (20%) died within 90 days of diagnosis and 37/198 (19%) of deaths occurred between days 29 and 90. Risk factors for mortality by day 90 days included age >65 years (1.8, 95% CI 1.3-2.4, P< 0.001), lung transplant (compared to non-lung) (1.6, 95% CI 1.1-2.4, P=0.02), chronic lung disease (2.2, 95% CI 1.5-3.4, P=0.002) and heart failure (1.9, 95% CI 1.2-2.9), which were similar to risk factors reported for 28-day mortality (Table 1). Diagnosis during the second half of 2020 (6/20-12/31/20) was associated with lower mortality by 28 days (aHR 0.7, 95% CI 0.5-1.0, P=0.03) compared to diagnosis during the early half of 2020 (3/1-6/19/20); however, mortality by 90 days was similar in the late and early time periods (aHR 0.9, 95% CI 0.7-1.2, P=0.54). Obesity and mTOR inhibitor use were also associated with death by 28 but not 90 days. Kaplan-Meier survival curves by time period of diagnosis are shown in Figure 1. Table 1. Multivariable Cox-Proportional Hazard Model for Mortality at 28 and 90-days Among Solid Organ Transplant Recipients Hospitalized for Covid-19 (N=979) Figure 1. Survival among SOT recipients hospitalized for Covid-19 by diagnosis time period Vertical tick marks represent censored cases. Early 2020 refers to cases diagnosed between March 1 and June 19, 2020 and late 2020 refers to cases diagnosed between June 20 and December 31, 2020. Conclusion Approximately 20% of deaths among SOTr hospitalized for Covid-19 occurred between days 29 and 90. Future investigations are required to discern the mechanism(s) for the improvement in early, but not late, mortality among SOTr with Covid-19 during the course of the pandemic. Disclosures Madeleine R. Heldman, MD, Cigna Lifesource (Other Financial or Material Support, Speaking honoraria)Thermo Fisher Scientific (Other Financial or Material Support, Speaking honoraria) Olivia S. Kates, MD, Merk (Scientific Research Study Investigator) Ajit P. Limaye, MD, astellas (Scientific Research Study Investigator)CTI (Scientific Research Study Investigator)GSK (Consultant)Johnson&Johnson (Other Financial or Material Support, Adjudication Committee)merck (Consultant, Grant/Research Support, Scientific Research Study Investigator)moderna (Scientific Research Study Investigator)Novartis (Other Financial or Material Support, DMC member)Novo Nordisk (Consultant)

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78. Acute Respiratory Illnesses in Children During the sars-cov-2 Pandemic: A Prospective Multicenter Surveillance Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.388 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S170-S171

Author(s):

Zaid Haddadin ◽

Jennifer E Schuster ◽

Andrew J Spieker ◽

Herdi Kurnia Rahman ◽

Laura S Stewart ◽

...

Keyword(s):

Research Study ◽

Vaccine Trial ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Respiratory Illnesses ◽

Study Investigator ◽

Support Research ◽

Research Grant

Abstract Background A state of emergency was declared in the United States (US) on March 13, 2020 in response to the SARS-CoV-2 pandemic. Healthcare providers had to alter practice patterns and research priorities. We assessed the frequency of acute respiratory illnesses (ARI) in children, notably those due to respiratory syncytial virus (RSV) and influenza, before and during the pandemic. Methods We conducted multi-center active prospective ARI surveillance in children as part of the New Vaccine Surveillance Network. Children < 18 years with fever and/or respiratory symptoms were enrolled in emergency department and inpatient settings at seven US medical centers over four respiratory seasons during 2016–2020 (Fig 1). Pandemic-related restrictions to patient access limited enrollment in some sites beginning March 2020. Respiratory specimens were collected and tested at each site for RSV and influenza by qRT-PCR. Data were analyzed by calendar weeks. We compared the cumulative proportions of RSV and influenza detection after week 13 in 2020 to the previous seasons using Fisher’s exact test. Figure 1. Numbers of Eligible and Enrolled Acute Respiratory Illness Cases, and Proportions of RSV and Influenza Detection by Week, Stratified by Study Season Results Of 44,247 eligible children, 25,375 (57%) were enrolled and tested for RSV and/or influenza. A total of 6351/25375 (25%) and 3446/25372 (14%) children were RSV and influenza-positive over the four seasons, respectively. In 2020, we noted a rapid drop in eligible and enrolled ARI subjects after weeks 11–13 (Fig 1). During weeks 13–18 in 2016–2019, the three-year average of eligible and enrolled subjects was 1802 and 978, respectively. However, over the same period in 2020, there were 675 eligible and 278 enrolled subjects, representing declines of 62.5% and 71.6% respectively (Fig 1). In 2020, there were no RSV or influenza cases detected in weeks 15–18, and the cumulative proportions of RSV and influenza detection after week 13 were lower compared to previous seasons (p< 0.001) (Figs 1 and 2). Figure 2. Cumulative Proportions of Weekly RSV and Influenza Detection by Study Season Conclusion There was a considerable decline in ARI visits and the proportion of RSV and influenza detection across seven distinct geographic sites during the pandemic compared with previous seasons. These findings might be attributable to social distancing measures to lessen the spread of SARS-CoV-2, changes in healthcare-seeking behaviors, and limited access to medical care. Disclosures Zaid Haddadin, MD, CDC (Grant/Research Support, Research Grant or Support)Quidel Corporation (Grant/Research Support, Research Grant or Support)sanofi pasteur (Grant/Research Support, Research Grant or Support) John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member)IDConnect (Advisor or Review Panel member)Quidel (Advisor or Review Panel member) Christopher J. Harrison, MD, GSK (Grant/Research Support, Infant menigiciccal B conjugate vaccine trial)Merck (Research Grant or Support, Infant pneumococcal conjugate vaccine trial) 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) 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)

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