Lack of Effects of the Presence of a Dog on Pain Perception in Healthy Participants—A Randomized Controlled Trial

Animal-assisted interventions (AAIs) have been shown to be effective in the treatment of pain. Studies suggest that relationships with animals can have comparable qualities to relationships with humans and that this enables animals to provide social support. Further, the presence of an animal can strengthen the therapeutic alliance between patients and treatment providers. This suggests that the analgesic effects of AAI might be mediated by social support from an animal or by strengthening the alliance between the patient and the treatment provider. To test these assumptions, we examined the effects of the presence of a dog on experimentally induced pain in a pain assessment and a pain therapy context. Hundred thirty-two healthy participants were randomly assigned to the conditions “pain,” “pain + dog,” “pain + placebo,” or “pain + placebo + dog.” We collected baseline and posttreatment measurements of heat-pain tolerance and the heat-pain threshold and of the corresponding subjective ratings of heat-pain intensity and unpleasantness as well as of participants' perceptions of the study investigator. The primary outcome was heat-pain tolerance. The presence of the dog did not influence the primary outcome (“pain” vs. “pain + dog”: difference = 0.04, CI = −0.66 to 0.74, p = 0.905; “pain + placebo” vs. “pain + placebo + dog”: difference = 0.43, CI = −0.02 to 0.88, p = 0.059). Participants did also not perceive the study investigator to be more trustworthy in the presence of the dog (“pain” vs. “pain + dog”: difference = 0.10, CI = −0.67 to 0.87, p = 0.796; “pain + placebo” vs. “pain + placebo + dog”: difference = 0.11, CI = −0.43 to 0.64, p = 0.695). The results indicate that the mere presence of a dog does not contribute to pain reduction and that the analgesic effects of AAI that previous studies have found is not replicated in our study as AAI did not increase perceived social support and had no effect on the alliance between the participant and the treatment provider. We assume that the animal most likely needs to be an integrated and plausible part of the treatment rationale so that participants are able to form a treatment-response expectation toward AAI.Clinical Trial Registration: This study was preregistered as a clinical trial on www.clinicaltrials.gov (Identifier: NCT0389814).

120. An open-label comparative trial of SUBA-itraconazole (SUBA) versus conventional itraconazole (c-itra) for treatment of proven and probable endemic mycoses (MSG-15): a pharmacokinetic (PK) and adverse Event (AE) analysis

Background C-itra is the drug of choice for treatment of most non-CNS, non-life-threatening forms of endemic mycoses (EM), including histoplasmosis, blastomycosis, coccidioidomycosis, sporotrichosis and talaromycosis. SUBA represents a new formulation of itraconazole that utilizes nanotechnology to improve bioavailability when administered orally. SUBA is formulated as nanoparticles allowing for absorption in the small bowel while not relying on gastric acidity for optimal absorption. MSG-15 is an open-label, comparative clinical trial comparing SUBA to c-itra for the treatment of EM. Herein we report the final PK and AE profiles of these two compounds. Methods Subjects with proven and probable EM were eligible this open-label comparative study. The protocol allowed up to 14 d of prior therapy with any antifungal for this episode of EM. Subjects were randomized to receive either SUBA 130 mg po bid or c-itra 200 mg po bid for up to 6 months. Follow up occurred at 7, 14, 28, 42, 84 and 180 d post-enrollment. PK samples were obtained at 7, 14, and 42 d. Clinical assessment, including symptom assessment, AEs, overall drug tolerance, and quality of life were assessed at each visit. We used descriptive statistics for this analysis. Results 89 subjects with EM entered the trial, including 43 on SUBA and 46 on c-itra. We measured PK serum levels of itra and hydroxyl-itra at days 7, 14, and 42 and these data are depicted in Figures 1-3. There were no significant differences in these levels, including combined itra/hydroxyl-itra levels, among the two study arms. AUC for itra and hydroxyl-itra were similar for both arms. AEs as assessed at each study evaluation were also quite similar among the two study arms. Overall, any AE occurred in 74% vs 85% of SUBA and c-itra recipients, respectively (NS). Drug-related AEs occurred in 35% vs 41% of SUBA and itra recipients, respectively (NS). Most common drug-related AEs included cardiovascular (edema and hypertension), nausea and loss of appetite. Combined Itraconazole and Hydroxy-itraconazole Concentration Over Time Conclusion Compared to c-itra, SUBA demonstrates almost identical serum levels despite being dosed at roughly 60% standard dosing for c-itra (130 mg po bid vs 200 mg po bid). SUBA is slightly better tolerated than c-itra, although the specific AEs are similar. Disclosures Peter G. Pappas, MD, Astellas (Research Grant or Support)Cidara (Research Grant or Support)F2G (Consultant)Matinas (Consultant, Scientific Research Study Investigator)Mayne Pharma (Research Grant or Support)Scynexis (Research Grant or Support) Andrej Spec, MD, MSCI, Mayne Pharma (Grant/Research Support) Marisa Miceli, MD, SCYNEXIS, Inc. (Advisor or Review Panel member) George R. R. Thompson III, III, MD, Amplyx (Consultant, Grant/Research Support)Appili (Consultant)Astellas (Consultant, Grant/Research Support)Avir (Grant/Research Support)Cidara (Consultant, Grant/Research Support)F2G (Consultant, Grant/Research Support)Mayne (Consultant, Grant/Research Support)Merck (Scientific Research Study Investigator)Pfizer (Advisor or Review Panel member)

161. Flucytosine Utilization and Dosing Practices at an Academic Medical Center

Background The typical dose of flucytosine is 25 mg/kg/dose every 6 hours for severe infections due to Candida and Cryptococcus. Many hospital protocols use ideal body weight (IBW) for initial dosing to achieve a goal peak serum concentration of 30-80 mcg/mL, but this is supported by very limited data. Our objective was to evaluate flucytosine dosing strategies, describe safety concerns, and explore financial benefits associated with using IBW. Methods All inpatient flucytosine orders for adults from 1/1/2015 through 10/31/2020 were retrospectively evaluated. Doses, weight used, flucytosine levels, adverse events, and potential cost savings associated with IBW dosing were characterized. Results During this period, 35 patients received flucytosine. The most common indications were cryptococcal meningitis (73%), pulmonary cryptococcosis (14%), and candidiasis (11%). Most patients were receiving concurrent liposomal amphotericin B (92%). Based on body mass index, most patients were overweight or obese (60%). Actual body weight was used for initial dosing in most cases (81%). Flucytosine peak monitoring was performed in 51% of cases. Initial peak levels were supratherapeutic in 10/19 cases (53%). Of those 10 patients, 70% were overweight/obese, and 60% would have received a lower initial dose if IBW had been used with dose rounding to the nearest 500mg capsule. Adverse events for all patients included new onset cytopenias, hepatic and renal dysfunction, occurring in 20%, 11%, and 60% respectively. Those with supratherapeutic levels had higher rates of new onset hepatic and renal dysfunction, 30% and 90% respectively. In 32% of cases, using IBW would have resulted in a lower daily dose, with an average dose reduction of 1888 mg, resulting in a mean cost savings per patient of &640/day using average wholesale price. Conclusion Most flucytosine orders were not dosed using IBW, which may have led to supratherapeutic levels. Using IBW for dosing in overweight patients may lead to reduced toxicity and potential cost savings. The default dosing weight for flucytosine in our electronic medical record will be set to IBW to encourage change. Disclosures Trevor C. Van Schooneveld, MD, FACP, BioFire (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Insmed (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Scientific Research Study Investigator; Rebiotix (Individual(s) Involved: Self): Scientific Research Study Investigator Bryan Alexander, PharmD, Astellas Pharma (Advisor or Review Panel member) Scott J. Bergman, PharmD, FCCP, FIDSA, BCPS, BCIDP, Merck & Co., Inc (Grant/Research Support) Scott J. Bergman, PharmD, FCCP, FIDSA, BCPS, BCIDP, Merck & Co., Inc (Individual(s) Involved: Self): Research Grant or Support

535. Comparison of Outcomes in Patients Positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection After Monoclonal Antibody Therapy (MAT) with Bamlamivimab or Casirivimab-Imdevimab

Background Limited options currently exist for treatment of patients diagnosed with symptomatic coronavirus 2019 (COVID-19). Monoclonal antibody therapy (MAT) has been investigated as a therapeutic option for symptomatic COVID-19 patients in the outpatient setting at high-risk for progression to severe disease based on emergency use authorization (EUA) criteria. No published studies have compared outcomes for patients treated with different MAT for COVID-19. Methods This was a single-center, retrospective cohort study at The Ohio State University Wexner Medical Center to compare COVID-19-related emergency room (ER) visits, admissions, and mortality at 30 days after MAT infusion for adult patients with symptomatic SARS-CoV-2 between November 16, 2020 and February 2, 2021 who received bamlanivimab versus those who received casirivimab-imdevimab. Statistical analysis used logistic regression analysis to determine the odds ratio (OR) to evaluate the relationship between patient characteristics, MAT, and outcomes. Results The cohort included 943 patients with SARS-CoV-2 who received MAT, including 658 patients who received bamlanivimab and 285 who received casirivimab-imdevimab. Outcome results between patients who received bamlanivimab and casirivimab-imdevimab showed no statistically significant difference seen in the number of COVID-19 related ER visits (3.2% vs 3.5%, p = 0.80), hospital admissions (4.6% vs 2.8%, p = 0.21), or mortality (0.5% vs 0.7%, p = 0.63). Multivariate analysis showed no statistically significant difference in outcomes between the groups when accounting for potential confounders. As reflected in the Table, chronic lymphocytic leukemia (CLL), gender, and asthma were associated with increased COVID-19 related ER visit within 30 days of infusion and age, chronic obstructive pulmonary disease, CLL, and lupus were associated with increased risk for COVID-19 related admission within 30 days of infusion. Age and obesity with body mass index greater than 35 mg/kg2 were associated with increased risk for COVID-19 related mortality at 30 days. Conclusion COVID-19 related outcomes were similar when comparing patients with COVID-19 treated with bamlanivimab versus those treated with casirivimab-imdevimab. Disclosures Mohammad Mahdee Sobhanie, M.D., Regeneron (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator, Was a sub-investigator for Regeneron 2066 and 2069) Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)

1340. The Burden of Influenza and Rhinovirus Among Hospitalized Adults Post the COVID-19 Pandemic

Background Acute respiratory tract infections (ARIs) are a significant cause of morbidity in adults. Influenza is associated with about 490,600 hospitalizations and 34,200 deaths in the US in the 2018-2019 season. The burden of rhinovirus among adults hospitalized with ARI is less well known. We compared the burden of influenza and rhinovirus from 2 consecutive winter respiratory viral seasons in hospitalized adults and healthy controls pre-COVID-19 and one season mid-COVID-19 to determine the impact of rhinovirus as a pathogen. Methods From Oct 2018 to Apr 2021, prospective surveillance of adults ≥50 years old admitted with ARI or COPD/CHF exacerbations at any age was conducted at two Atlanta hospitals. Adults were eligible if they lived within an eight-county region around Atlanta and if their symptom duration was < 14 days. In the seasons from Oct 2018 to Mar 2020, asymptomatic adults ≥50 years old were enrolled as controls. Standard of care test results were included and those enrolled contributed nasopharyngeal swabs that were tested for respiratory pathogens using BioFire® FilmArray® Respiratory Viral Panel (RVP). Results During the first two seasons, 1566 hospitalized adults were enrolled. Rhinovirus was detected in 7.5% (118) and influenza was detected in 7.7% (121). Rhinovirus was also detected in 2.2% of 466 healthy adult controls while influenza was detected in 0%. During Season 3, the peak of the COVID-19 pandemic, influenza declined to 0% of ARI hospitalizations. Rhinovirus also declined (p=0.01) but still accounted for 5.1% of all ARIs screened (Figure 1). Rhinovirus was detected at a greater rate in Season 3 than in asymptomatic controls in the first 2 seasons (p=0.008). In the first two seasons, Influenza was detected in 8.6% (24/276) of those admitted to the ICU. Rhinovirus was detected in 6.1% (17/276) of those admitted to the ICU but declined to 3.1% (8/258) in Season 3. Figure 1. Percent Positive Cases of Influenza and Rhinovirus between Season 1&2 (hospitalized and healthy controls) vs Season 3 (hospitalized) Conclusion Dramatic declines occurred in influenza in adults hospitalized with ARI, CHF, or COPD in Atlanta during the COVID-19 pandemic and with enhanced public health measures. Although rhinovirus declined during the COVID-19 pandemic, it continued to be identified at a rate higher than in historical controls. Additional data are needed to understand the role of rhinovirus in adult ARI, CHF, and COPD exacerbations. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory; Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel member)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

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

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)

1334. Outcomes Among Influenza and SARS-CoV-2 Infection in Hospitalized Adults Age ≥ 50 Years and with Underlying Chronic Obstructive Pulmonary Disease (COPD) or Congestive Heart Failure (CHF)

Background A significant burden of disease exists for adults infected with influenza (flu) and SARS-CoV-2, which causes COVID-19. However, data are limited comparing outcomes between hospitalized adults infected with these viruses. Methods Over the course of 3 consecutive winter respiratory viral seasons, adults ≥ 50 years of age admitted with acute respiratory tract infections (ARI) and adults of any age with COPD or CHF-related admissions were enrolled from 2 Atlanta area hospitals. For the 2018-19 and 2019-20 seasons, participants were approached in the hospital. If the participant enrolled, nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected and tested using BioFire® FilmArray® respiratory panel. Due to the COVID-19 pandemic in 2020-21 and limitations involving participant contact, only NP standard of care (SOC) swabs were collected. A comprehensive medical chart review was completed for each subject which encompassed data on their hospitalization, past medical history, and vaccination history. Co-infected patients were excluded from the analyses. Results Of the eligible participants, 118 were flu positive (three RSV-influenza co-infections were excluded) and 527 were COVID-19 positive. Median age was lower for the flu cohort at 62 (IQR 56-71) than those with COVID-19 (67, IQR 59-77) (p < 0.0001). Length of stay (LOS) was shorter in flu-infected patients (median 3 d, IQR 2-6), but was longer for COVID-19 patients (median 5 d, IQR 3-10). ICU admission occurred in 20% of those with flu, and among those admitted to the ICU mechanical ventilation (MV) occurred in 12.5%. ICU admission and MV was significantly higher for those with COVID-19, with 28% of patients admitted to the ICU and 47% of those requiring MV. Among patients with COVID-19, 8.9% died. This was significantly higher than that of flu (3.4%) (p=0.008). Hospital discharge occurred more frequently to a nursing home or LTCF with COVID-19 (10.3%) than with flu (0%) (p< 0.0001). Table 1. Breakdown of age, hospitalization course, and discharge disposition for participants diagnosed with influenza or COVID-19 during hospitalization. Conclusion COVID-19 resulted in a longer hospital admission, a greater chance of ICU admission and MV as compared to flu. Additionally, COVID-19 participants had a high rate of discharge to a nursing home/LTCF and a significantly higher risk of death. While the clinical course was not as severe as COVID-19, influenza contributed a significant burden. Disclosures David L. Swerdlow, MD, Pfizer Vaccines (Employee) Robin Hubler, MS, Pfizer Inc. (Employee) Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Janssen, Merck, Moderna, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Meissa Vaccines (Other Financial or Material Support, Co-inventor of patented RSV vaccine technology unrelated to this manuscript, which has been licensed to Meissa Vaccines, Inc.) Larry Anderson, MD, ADVI (Consultant)Bavarian Nordic (Consultant)Novavax (Consultant)Phizer (Grant/Research Support, Scientific Research Study Investigator)Sciogen (Research Grant or Support) Nadine Rouphael, MD, pfizer, sanofi, lily, quidel, merck (Grant/Research Support) Nadine Rouphael, MD, Lilly (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Merck (Individual(s) Involved: Self): Emory study PI, Grant/Research Support; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Pfizer (Individual(s) Involved: Self): Grant/Research Support, I conduct as co-PI the RSV PFIZER study at Emory; Quidel (Individual(s) Involved: Self): Emory Study PI, Grant/Research Support; Sanofi Pasteur (Individual(s) Involved: Self): Chair phase 3 COVID vaccine, Grant/Research Support Evan J. Anderson, MD, GSK (Scientific Research Study Investigator)Janssen (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member)Kentucky Bioprocessing, Inc (Advisor or Review Panel member)MedImmune (Scientific Research Study Investigator)Medscape (Consultant)Merck (Scientific Research Study Investigator)Micron (Scientific Research Study Investigator)PaxVax (Scientific Research Study Investigator)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Scientific Research Study Investigator)

822. Tenofovir Alafenamide (TAF) is an Independent Risk Factor for Hyperlipidemia in Persons with Human Immunodeficiency Virus (HIV) on Antiretroviral Therapy (ART)

Background ART-associated weight gain, metabolic disorders, and co-morbidities such as cardiovascular disease are challenges in long-term human immunodeficiency virus (HIV) care. We explore the effects of different ART classes on lipids at The Ohio State University Medical Center Infectious Diseases Clinic. Methods This was a retrospective, cohort study of adult PWH on ART for ≥ 3 months seen at our clinic from 1/1/2015 to 1/1/2017. Patients with CD4+ count < 200 cells/mm3 and viral load >200 copies/mL, history of malignancy, or pregnancy were excluded. Lipid values were collected over the study period. The primary outcome was change in total cholesterol (TC), high density lipoprotein (HDL) cholesterol, and non-HDL cholesterol over the study period. Multivariable regression was used to model these outcomes. Results Among 411 PWH who met criteria, 87.4% were male, and 43.3% had a baseline diagnosis of hyperlipidemia. 21.1% were on a protease inhibitor (PI), 45% were on a non-nucleoside reverse transcriptase inhibitor (NNRTI), and 37% were on an integrase strand transfer inhibitor (INSTI). 70.1% were on tenofovir disoproxil fumarate (TDF)/ emtricitabine (FTC), 20.7% were on abacavir (ABC)/ lamivudine (3TC), and 4.4% were on TAF/FTC. The mean population (MP) difference in TC was -1.54 ± 1.34 mg/dL (p=0.25), the MP difference in non-HDL cholesterol was -1.78 ± 1.26 mg/dL (p=0.16), and the MP difference in HDL cholesterol was 0.24 ± 0.43 mg/dL (p=0.6). In multivariable linear regression models (Table 1), TAF/FTC was associated with a change of TC of 18.2 ± 6.4 mg/dL (P= 0.005), a change of non-HDL cholesterol of 12.0 ± 6.0 mg/dL (p=0.046), and a change of HDL cholesterol of 6.2 ± 2.1 mg/dL (p=0.003). These models included terms for months of follow up, male gender and baseline hyperlipidemia. Though race, diabetes mellitus, and ethnicity were not significant in the model, after adjustments for them, PWH on TAF/FTC showed a change of TC of 18.0 ± 6.4 mg/dL (p=0.005), a change of non-HDL cholesterol of 11.8 ± 6.0 mg/dL (P=0.051), and a change of HDL of 6.2 ± 2.1 (p=0.03). Multivariable Linear Regression Models for Change in Total Cholesterol and Non-HDL Cholesterol Conclusion Prior studies have shown an increase in lipid levels associated with TAF compared to TDF. This study shows that TAF is an independent risk factor for increased TC, non-HDL cholesterol, and HDL cholesterol in the PWH population as a whole. Disclosures Carlos Malvestutto, M.D., Lilly (Scientific Research Study Investigator)Regeneron Inc. (Scientific Research Study Investigator)ViiV Healthcare (Advisor or Review Panel member)

1282. Ceftolozane/Tazobactam Use in Critically Ill Patients Receiving Intermittent or Continuous Renal Replacement Therapy

Background Our hospital recommends ceftolozane/tazobactam (CT) as a broad-spectrum agent for treatment of Gram-negative bacilli in patients with a recent or current multidrug resistant (MDR) Pseudomonas infection. CT is utilized in patients who are on renal replacement therapy (RRT) yet little data exist on the efficacy in this population. Currently there are no FDA-approved dosing recommendations for patients on continuous veno-venous hemodialysis (CVVHD). The purpose of this study was to describe the indications, dosing and outcomes of patients on CT while receiving RRT. Methods All patients receiving CT from 2015-20 were included if on RRT, either CVVHD or intermittent hemodialysis (iHD). Clinical success was defined as the absence of pre-treatment signs/symptoms and/or no escalated antibiotic treatment within 48 hours of completing therapy. 30-day mortality was defined as death from any cause within 30 days of CT completion. Patients treated after 2019 approval of higher dosing for hospital-associated/ventilator-acquired pneumonia (HAP/VAP) were noted. Results 17 patients received 24 courses of CT while on RRT, 9 (53%) were immunocompromised. All patients were treated in the ICU for an MDR Pseudomonas infection. As shown in table 1, the most common indications were 49% HAP/VAP, 17% complicated intra-abdominal (cIAI), or 17% urinary tract infections (cUTI). 4 (24%) patients had additional treatment courses of CT started empirically when infection was suspected. Median time to initiation for all courses was 2 days after obtaining cultures and median duration was 7 days. 12 patients were on CVVHD (median flow rate 2.5L/hr) and 7 were on iHD. 2 patients received iHD after CVVHD. Median dose while on CVVHD was 1500mg every 8 hours. The median dose on iHD was that approved by FDA for cIAI and cUTI: 750mg x1 followed by 150mg every 8 hours. Clinical success was achieved in 12 (71%) patients and 30-day mortality was 8 (47%). Table 1: Details on first courses of CT for patients on RRT *Denotes treatment after 2019 FDA approval of 3g q8h for treatment of HAP/VAP in patients with normal renal function **Flow rate: Medium 1.5-2L/hr; High: >2.5L/hr +NA denotes patient that had passed away and therefore additional C/T courses were not applicable Conclusion This case series provides real-world results of outcomes for critically ill patients on RRT treated with CT. Clinical success rates were similar to other published literature despite the severity of illness of this cohort, which is corroborated by the high 30 day, all-cause mortality. Ultimately, further evaluation of CT dosing in patients on RRT is warranted. Disclosures Laura A. Puzniak, PhD, Merck & Co., Inc. (Employee) Kelly Harris, PharmD, BCPS, Merck & Co. Inc (Employee) Trevor C. Van Schooneveld, MD, FACP, BioFire (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Insmed (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Scientific Research Study Investigator; Rebiotix (Individual(s) Involved: Self): Scientific Research Study Investigator Scott J. Bergman, PharmD, FCCP, FIDSA, BCPS, BCIDP, Merck & Co., Inc (Grant/Research Support) Scott J. Bergman, PharmD, FCCP, FIDSA, BCPS, BCIDP, Merck & Co., Inc (Individual(s) Involved: Self): Research Grant or Support

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

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)