scholarly journals 1266. Melatonin for Renal Protection of Patients Treated with Polymyxin B: A Double Blind Randomized Clinical Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S721-S721
Author(s):  
Maria Helena Rigatto ◽  
Pedro Bergo ◽  
Giulia Baldissera ◽  
Eduarda Beck ◽  
Leonardo David ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Failure ◽  
Randomized Clinical Trial ◽  
Research Study ◽  
Scientific Research ◽  
Polymyxin B ◽  
Renal Protection ◽  
Research Support ◽  
Double Blind ◽  
Study Investigator

Abstract Background Polymyxins are one of the last resort treatments for carbapenem resistant gram-negative infections. Nephrotoxicity is its main adverse effect and has been related to oxidative stress mechanisms. Melatonin was associated to reduction in polymyxins nephrotoxicity in animal studies. Our objective is to evaluate the effect of melatonin on renal protection of patients receiving polymyxin B. Methods We did a single center, double blind, randomized clinical trial (NCT03725267) of melatonin 30mg versus placebo for patients treated with polymyxin B from October 2018 to April 2021, in Porto Alegre, Brazil. Patients ≥18 years old, receiving polymyxin B for ≤48 hours, who accepted informed consent terms were included and excluded if intensive care unit (ICU) admission at enrollment, estimated glomerular rate estimated glomerular rate < 10ml/min, dialysis or previous melatonin use. Treatment with melatonin or placebo was randomized in blocks of 4 and maintained until the end of polymyxin B treatment of for a maximum of 14 days. Our main outcome was any level of nephrotoxicity by RIFLE score. Secondary outcomes were renal failure and need for dialysis. We estimated a sample size of 100 patients, however the study had to be stopped earlier due to recruitment restrictions imposed by the COVID-19 pandemic. Results Eighty-eight patients were randomized, 44 received melatonin and 44 received identical placebo pills. Patients had a mean age of 63.6±17.3 years, 60.2% were male, and had a median Charlson index of 5 (3-8.3). Most infections (79.5%) were microbiologically confirmed, having 68.6% Klebsiella sp isolated. Urinary tract accounted for47.7% of infection sites. Median time of polymyxin B therapy was 9.1±6.6 days. Combination therapy was prescribed for 89.8% of patients and 38.6% received at least another nephrotoxic drug. All variables were equally distributed among groups. Nephrotoxicity rates occurred in 23 of 44 (52.3%) in both groups, P=0.99. Patients who developed renal failure were 8(18.2%) vs 9(20.5%) and dialysis occurred in 4(9.1%) vs 5 (11.4%) of melatonin and placebo groups respectively. Conclusion Melatonin did not show a clinically significant renal protective effect in patients treated with polymyxin B. Disclosures Maria Helena Rigatto, MD, PhD, CNPq (Grant/Research Support) Diego Rodrigues Falci, MD, MSc, PhD, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)GSK (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)MSD (Speaker’s Bureau)Pfizer (Speaker’s Bureau)United Medical (Speaker’s Bureau, Other Financial or Material Support) Alexandre Zavascki, MD, PhD, Pfizer (Grant/Research Support)

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

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)

scholarly journals 502. Early COVID-19 Treatment with SARS-CoV-2 Neutralizing Antibody Sotrovimab

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S353-S354
Author(s):  
Anil K Gupta ◽  
Yaneicy Gonzalez Rojas ◽  
Erick Juarez ◽  
Manuel Crespo Casal ◽  
Jaynier Moya ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
Illness Management ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Study Investigator ◽  
Trial Investigator

Abstract Background COVID-19 disproportionately results in hospitalization and death in older patients and those with underlying comorbidities. Sotrovimab is a pan-sarbecovirus monoclonal antibody that binds a highly conserved epitope of the SARS-CoV-2 receptor binding domain and has an Fc modification that increases half-life. Sotrovimab retains activity against UK, S. Africa, Brazil, India, New York and California variants in vitro. Objectives To evaluate the efficacy and safety of treatment with sotrovimab in high-risk, non-hospitalized patients with mild/moderate COVID-19, as part of the COMET-ICE clinical trial. Methods Multicenter, double-blind, phase 3 trial in non-hospitalized patients with symptomatic COVID-19 and ≥1 risk factor for disease progression were randomized 1:1 to an IV infusion of sotrovimab 500 mg or placebo. The primary efficacy endpoint was the proportion of patients with COVID-19 progression, defined as hospitalization > 24 hours or death, due to any cause, ≤29 days of randomization. Results The study met the pre-defined primary efficacy endpoint in a preplanned interim analysis: the risk of COVID-19 progression was significantly reduced by 85% (97.24% CI, 44% to 96%; P = 0.002) in 583 patients. In the final intention-to-treat analysis (N = 1057), the adjusted relative risk reduction was 79% (95% CI, 50% to 91%; p< 0.001) through Day 29 in recipients of sotrovimab (n=528) vs. placebo (n=529). Treatment with sotrovimab (ITT) resulted in a numerical reduction in the need for ER visits for illness management, hospitalization for acute illness management (any duration) or death (any cause) compared to placebo. No participants on sotrovimab required ICU admission, compared to 9 participants on placebo, of whom 4 participants required mechanical ventilation. No participants who received sotrovimab died, compared to 4 participants on placebo. The incidence of adverse events was similar between treatment arms and SAEs were numerically more common in the placebo arm. Conclusion Treatment with sotrovimab 500 mg IV resulted in a clinically and statistically significant reduction in progression of COVID-19 to hospitalization or death in patients with mild/moderate disease and was well-tolerated. Study funding GSK & VIR; NCT04545060 Disclosures Jaynier Moya, MD, VIR Biotechnology (Other Financial or Material Support, Jaynier Moya received non-financial support for serving as a clinical trial investigator for Vir Biotechnology) Diego Rodrigues Falci, MD, MSc, PhD, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker's Bureau)GSK (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)MSD (Speaker's Bureau)Pfizer (Speaker's Bureau)United Medical (Speaker's Bureau, Other Financial or Material Support) Joel Solis, MD, VIR Biotechnology (Other Financial or Material Support, Joel Solis received non-financial support for serving as a clinical trial investigator for Vir Biotechnology) Hanzhe Zheng, PhD, VIR Biotechnology (Employee) Nicola Scott, MSc, GlaxoSmithKline (Employee, Shareholder) Andrea L. Cathcart, PhD, Gilead (Shareholder)VIR (Employee, Shareholder) Christy Hebner, PhD, Vir Biotechnology (Employee, Shareholder) Jennifer Sager, PhD, GSK (Other Financial or Material Support)Vir Biotechnology (Employee, Shareholder) Erik Mogalian, PharmD, PhD, Vir Biotechnology (Employee, Shareholder) Daren Austin, PhD, GlaxoSmithKline (Employee, Shareholder) Amanda Peppercorn, MD, GlaxoSmithKline (Employee) Elizabeth L. Alexander, MD, MSc, GlaxoSmithKline (Grant/Research Support, Other Financial or Material Support)VIR Biotechnology (Employee, Shareholder, GSK pharmaceuticals) Wendy W. Yeh, MD, Vir Biotechnology (Employee) Almena Free, MD, Amgen (Scientific Research Study Investigator)Astra Zeneca (Scientific Research Study Investigator)Cardurian (Scientific Research Study Investigator)Coherus (Scientific Research Study Investigator)Freenome (Scientific Research Study Investigator)GlaxoSmithKline/Vir (Scientific Research Study Investigator)Ionis (Scientific Research Study Investigator)Kowa (Scientific Research Study Investigator)New Amsterdam (Scientific Research Study Investigator)Regenacy (Scientific Research Study Investigator)Romark (Scientific Research Study Investigator)Scynexis (Scientific Research Study Investigator) Cynthia Brinson, MD, Abbvie (Scientific Research Study Investigator)BI (Scientific Research Study Investigator)Gilead Sciences Inc. (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau, Personal fees)GSK (Scientific Research Study Investigator)Novo Nordisk (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau) Melissa Aldinger, PharmD, VIR Biotechnology (Employee) Adrienne Shapiro, MD, PhD, Vir Biotechnology (Scientific Research Study Investigator)

scholarly journals 1184. A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Interchangeability of V114 and Prevnar 13™ with Respect to Safety, Tolerability, and Immunogenicity in Healthy Infants (PNEU-DIRECTION)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S684-S684
Author(s):  
Adroniki Bili ◽  
Scott Dobson ◽  
Jeffrey Quinones ◽  
Wanatpreeya Phongsamart ◽  
Peninnah Oberdorfer ◽  
...  
Keyword(s):  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
Research Support ◽  
Review Panel ◽  
Post Dose ◽  
Double Blind ◽  
Study Investigator ◽  
Group 1 ◽  
Research Grant

Abstract Background Pneumococcal diseases (PD) caused by Streptococcus pneumoniae are a major health concern globally. In children, currently licensed pneumococcal conjugate vaccines (PCVs) provide protection against PD from vaccine serotypes, but other non-vaccine serotypes have emerged and contribute to most residual disease. V114 is a 15-valent investigational PCV containing serotypes 22F and 33F in addition to the 13 serotypes shared by Prevnar 13TM (PCV13). This phase 3 study evaluated safety and immunogenicity of mixed PCV13/V114 regimens when changing from PCV13 to V114 at doses 2, 3, or 4. Methods In this double-blind trial, 900 infants were randomized in equal ratios to five treatment groups using a 3 + 1 immunization schedule (3-dose infant primary series followed by one toddler dose). Groups 2, 3, and 4 started with PCV13 and switched to V114 at doses 4, 3, and 2, respectively. Groups 1 and 5 received four doses of PCV13 and V114, respectively. Immunoglobulin G (IgG) responses to the 15 pneumococcal serotypes in V114 were measured at 30 days post-dose 3, prior to dose 4, and 30 days post-dose 4 (PD4). Primary immunogenicity analysis was based on 13 shared serotype responses at PD4. Safety was evaluated as the proportion of participants with adverse events (AEs). Results At 30 days PD4, IgG geometric mean concentrations (GMCs) for the 13 shared serotypes were generally comparable between V114/PCV13 mixed regimens (Groups 2-4) and participants that received the 4-dose PCV13 regimen (Group 1). Additionally, IgG GMCs for the 13 shared serotypes were generally comparable for participants that received the 4-dose V114 regimen (Group 5) and participants that received the 4-dose PCV13 regimen (Group 1). Infants given at least one dose of V114 mounted immune responses to two unique serotypes in V114 (22F and 33F). Frequency of injection-site and systemic AEs among study participants were generally comparable across all study groups. Conclusion V114 was well tolerated with a generally comparable safety profile to PCV13. For the 13 shared serotypes, both mixed-dose and 4-dose regimens of V114 induced generally comparable antibody responses to a PCV13 4-dose regimen. Study results support interchangeability of V114 with PCV13 in infants. Disclosures Adroniki Bili, MD, Merck & Co., Inc. (Employee, Shareholder) Ron Dagan, MD, Medimmune/AstraZeneca (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)MSD (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau) Marissa B. Wilck, MD, Merck & Co., Inc. (Employee, Shareholder) Waldimir Vallejos, MD, Merck & Co., Inc. (Employee, Shareholder) Christine Nunn, MS, Merck & Co., Inc. (Employee, Shareholder) Richard McFetridge, B.S., Merck & Co., Inc (Employee) Rong Fu, PhD, MSD China (Employee, Shareholder) Robert Lupinacci, M.S, Merck & Co., Inc (Employee, Shareholder) Luwy Musey, MD, Merck & Co., Inc. (Employee) Kara Bickham, MD, Merck Sharp and Dohme (Employee, Shareholder)

scholarly journals 40. Lenzilumab Efficacy and Safety in Newly Hospitalized COVID-19 Subjects: Results From a Phase 3 Randomized Double-Blind Placebo-Controlled Trial

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S29-S29
Author(s):  
Zelalem Temesgem ◽  
Charles Burger ◽  
Jason Baker ◽  
Christopher Polk ◽  
Claudia R Libertin ◽  
...  
Keyword(s):  
Research Study ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Scientific Research ◽  
Research Support ◽  
Phase 3 ◽  
Double Blind ◽  
Gm Csf ◽  
Study Investigator ◽  
Research Grant

Abstract Background Severe coronavirus disease 2019 (COVID-19) often results from the immune-mediated cytokine storm, triggered by granulocyte macrophage-colony stimulating factor (GM-CSF), potentially leading to respiratory failure and death. Lenzilumab, a novel anti-human GM-CSF monoclonal antibody, neutralizes GM-CSF and demonstrated potential to improve clinical outcomes in a matched case-cohort study of patients with severe COVID-19 pneumonia. This Phase 3 randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of lenzilumab to improve the likelihood of survival without invasive mechanical ventilation (SWOV), beyond available treatments. Methods Hypoxic patients, hospitalized with COVID-19 (n=520), requiring supplemental oxygen, but not invasive mechanical ventilation, were randomized on Day 0 to receive lenzilumab (1800mg, n=261) or placebo (n=259), and available treatments, including remdesivir and/or corticosteroids; and were followed through Day 28. Results Baseline demographics were comparable between groups: male, 64.7%; mean age, 60.5 years; median CRP, 79.0 mg/L. Patients across both groups received steroids (93.7%), remdesivir (72.4%), or both (69.1%). Lenzilumab improved the primary endpoint, likelihood of SWOV in the mITT population, by 1.54-fold (HR: 1.54; 95%CI: 1.02-2.32, p=0.0403). Lenzilumab improved SWOV by 1.91-fold (nominal p=0.0073) and 1.92-fold (nominal p=0.0067) in patients receiving remdesivir or remdesivir and corticosteroids, respectively. A key secondary endpoint of incidence of IMV, ECMO or death was also improved in patients receiving remdesivir (p=0.020) or remdesivir and corticosteroids (p=0.0180). Treatment-emergent serious adverse events were similar across both groups. Conclusion Lenzilumab significantly improved SWOV in hypoxic COVID-19 patients upon hospitalization, with the greatest benefit observed in patients receiving treatment with remdesivir and corticosteroids. NCT04351152 Disclosures Zelalem Temesgem, MD, Humanigen, Inc (Grant/Research Support) Jason Baker, MD, Humanigen, Inc (Grant/Research Support) Christopher Polk, MD, Atea (Research Grant or Support)Gilead (Advisor or Review Panel member, Research Grant or Support)Humanigen (Research Grant or Support)Regeneron (Research Grant or Support) Claudia R. Libertin, MD, Gilead (Grant/Research Support) Colleen F. Kelley, MD, MPH, Gilead Sciences (Individual(s) Involved: Self): Grant/Research Support; Moderna (Individual(s) Involved: Self): Grant/Research Support; Novavax (Individual(s) Involved: Self): Grant/Research Support; Viiv (Individual(s) Involved: Self): Grant/Research Support Vincent Marconi, MD, Bayer (Consultant, Scientific Research Study Investigator)Eli Lilly (Consultant, Scientific Research Study Investigator)Gilead Sciences (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator) Victoria Catterson, PhD, Humanigen, Inc (Consultant) William Aronstein, MD, PhD, Humanigen, Inc (Consultant) Cameron Durrant, MD, Humanigen, Inc (Employee) Dale Chappell, MD, Humanigen, Inc (Employee) Omar Ahmed, PharmD, Humanigen, Inc (Employee) Gabrielle Chappell, MSc, Humanigen, Inc (Consultant) Andrew Badley, M.D., AbbVie (Consultant) for the LIVE-AIR Study Group, n/a, Humanigen, Inc (Grant/Research Support)

scholarly journals 1506. Burden of Respiratory Syncytial Virus (RSV) and Other Lower Respiratory Tract Viral Infections During the First Two Years of Life: a Prospective Study

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S756-S756
Author(s):  
Shabir A Madhi ◽  
Ana Ceballos ◽  
Jo Ann Colas ◽  
Luis Cousin ◽  
Ulises D’Andrea ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Nasal Swab ◽  
Research Study ◽  
Viral Infections ◽  
Scientific Research ◽  
Human Clinical Trial ◽  
Research Support ◽  
Material Support ◽  
Study Investigator ◽  
Research Grant

Abstract Background Lower respiratory tract infections (LRTIs) are a leading cause of pediatric morbidity and mortality worldwide, with ~650,000 deaths recorded in < 5-year-olds in 2016. Cross-sectional studies on hospitalized LRTIs are available, but longitudinal studies on the total burden of viral LRTIs are scarce. This study (NCT01995175) prospectively collected incident RSV and other viral LRTIs in a multinational cohort. Methods From 2013 to 2017, infants in 8 countries were enrolled at birth and followed for LRTIs up to 2 years of age. Infants with suspected LRTIs were clinically examined and swabbed. Nasal swab samples were tested using quantitative real-time PCR for RSV and multiplex PCR panel for 16 other respiratory viruses/subtypes; bacterial culture was not performed. LRTI and severe LRTI episodes were defined per 2015 WHO LRTI case definitions. Viruses detected from nasal swabs collected from participants with WHO-defined LRTI and severe LRTI episodes are reported. Results The 2401 infants followed experienced 1012 LRTI episodes; 259 of these were severe LRTIs. At least 1 virus was detected from 909 (90%) and 235 (91%) LRTI and severe LRTI episodes, respectively. Enteroviruses/Rhinoviruses (EV/RV, 49%) were detected most frequently in samples collected from LRTI episodes, followed by RSV (22%), parainfluenza (PIV, 14%), human metapneumovirus (hMPV, 8%) and seasonal coronavirus (CoV, 6%). RSV was detected in 39% of samples from LRTI episodes in < 3-month-olds and in 18% of 1-year-olds (Table 1). In a similar trend, RSV was detected in 47% of samples from severe LRTI episodes in < 3-month-olds and in 21% of 1-year-olds (Table 2). Co-infection with another virus was common in CoV-positive samples (67%), while most samples positive for RSV (71%), hMPV (70%), EV/RV (67%) and PIV (58%) had no other virus detected. Table 1. Occurrence of laboratory confirmed respiratory viral infections by viral pathogens identified in nasal swab samples from WHO-defined LRTI episodes Table 2. Occurrence of laboratory confirmed respiratory viral infections by viral pathogens identified in nasal swab samples from WHO-defined severe LRTI episodes Conclusion Respiratory viruses are detected in the majority of LRTIs during the first 2 years of life. RSV likely accounts for much of this overall LRTI burden. Our results suggest that RSV most strongly impacted the very young; it was the most commonly detected virus in severe LRTIs in infants aged < 3 months. RSV was also persistently detected at high levels in samples from LRTIs (22%) and severe LRTIs (28%) in children up to 2 years old. Funding GlaxoSmithKline Biologicals SA Disclosures Ana Ceballos, MD, GSK group of companies (Scientific Research Study Investigator) Jo Ann Colas, MSc, GSK group of companies (Consultant) Luis Cousin, MD, Tecnología en Investigación (Scientific Research Study Investigator) Ilse Dieussaert, IR, GSK group of companies (Employee, Shareholder) Joseph B. Domachowske, MD, Astra Zeneca (Other Financial or Material Support, Grant/Research Support paid to my Institution on my behalf for sponsored human clinical trial activities)GSK group of companies (Other Financial or Material Support, Grant/Research Support paid to my Institution on my behalf for sponsored human clinical trial activities)Merck (Other Financial or Material Support, Grant/Research Support paid to my Institution on my behalf for sponsored human clinical trial activities) 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) Sanjay Gandhi, MD, GSK group of companies (Employee) Mélanie Hercor, PhD, GSK group of companies (Employee) Magali de Heusch, PhD, GSK group of companies (Employee) Joanne M. Langley, MD, GSK group of companies (Research Grant or Support)Immunivaccines Inc (Scientific Research Study Investigator, Research Grant or Support)Janssen (Research Grant or Support)Pfizer (Research Grant or Support)Symvivo (Scientific Research Study Investigator, Research Grant or Support)VBI Vaccines (Research Grant or Support) Amanda Leach, MRCPCH, GSK group of companies (Employee) Timo Vesikari, MD, PhD, Denka (Consultant) Sonia K. Stoszek, PhD, GSK group of companies (Employee, Shareholder)

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

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)

scholarly journals 1510. Infant Pneumonia and Subsequent Risk of Chronic Respiratory Disorders

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S758-S759
Author(s):  
Stephen I Pelton ◽  
Rotem Lapidot ◽  
Matthew Wasserman ◽  
Melody Shaff ◽  
Ahuva Hanau ◽  
...  
Keyword(s):  
Research Study ◽  
Scientific Research ◽  
Airway Disease ◽  
Research Support ◽  
Recurrent Wheezing ◽  
Recurrent Pneumonia ◽  
Respiratory Disorders ◽  
Study Investigator ◽  
Study Population ◽  
Research Grant

Abstract Background Community-acquired pneumonia (CAP) in infancy (i.e., among children aged < 2 years) may have long-term consequences for the rapidly developing lung. We examined the impact of pneumonia in infancy on subsequent respiratory health. Methods A retrospective matched-cohort design and data from Optum’s de-identified Integrated Claims-Clinical dataset (2009-2018) were employed. Study population comprised children who were hospitalized for CAP before age 2 years (“CAP patients”) as well as matched comparators without evidence of pneumonia before age 2 years (“comparison patients”). CAP patients and comparison patients were matched (fixed 1:5 ratio, without replacement) using estimated propensity scores and a nearest-neighbor approach; those with evidence of selected medical conditions (e.g., extreme prematurity, congenital diseases, respiratory diseases) before age 2 years were excluded. Study outcomes included recurrent pneumonia and a composite of asthma, recurrent wheezing, and hyperactive airway disease. Rates of study outcomes from age 2 to 5 years were estimated for all CAP and comparison patients as well as subgroups of CAP patients (and corresponding comparison patients) stratified by etiology (bacterial, viral, unspecified). Results Study population totaled 1,343 CAP patients and 6,715 comparison patients. CAP patients and comparison patients were well-balanced on their baseline characteristics and mean duration of follow-up was 757 and 729 days, respectively. Rates of chronic respiratory disorders from age 2 to 5 years were significantly higher among CAP patients versus comparison patients. Analyses of subgroups stratified by etiology demonstrated higher rates of study outcomes among CAP patients across all strata. Rates of recurrent pneumonia and a composite of asthma, recurrent wheezing, and hyperactive airway disease from age 2 to 5 years among CAP patients and matched comparison patients Conclusion Infant CAP foreshadows an increase in subsequent risk of chronic respiratory disorders. Further studies are needed to determine whether this elevated risk is due to infant pneumonia or whether infant pneumonia is a marker of at-risk children. Disclosures 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) Rotem Lapidot, MD, MSCI, Pfizer (Consultant) Matthew Wasserman, MSc., Pfizer Inc. (Employee) 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) Derek Weycker, PhD, Pfizer Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)

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

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S137-S138
Author(s):  
J P Sanchez ◽  
German Contreras ◽  
Truc T Tran ◽  
Shelby Simar ◽  
Blake Hanson ◽  
...  
Keyword(s):  
Research Study ◽  
Scientific Research ◽  
Kidney Injury ◽  
Bloodstream Infections ◽  
Definitive Treatment ◽  
Cancer Center ◽  
Future Research ◽  
Research Support ◽  
Patients With Cancer ◽  
Study Investigator

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

scholarly journals 43. A Pharmacoepidemiologic Evaluation of Echinocandin Use

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S45-S45
Author(s):  
Jinhee Jo ◽  
Joshua Hendrickson ◽  
Anne J Gonzales-Luna ◽  
Nicholas D Beyda ◽  
Kevin W Garey
Keyword(s):  
Hospital Admission ◽  
Invasive Candidiasis ◽  
Research Study ◽  
Medical Center ◽  
Significant Proportion ◽  
Scientific Research ◽  
Panel Member ◽  
Research Support ◽  
Study Investigator ◽  
Days Of Therapy

Abstract Background Invasive candidiasis (IC) is a common healthcare-associated infection. Rates of IC caused by drug-resistant Candida spp., designated by the CDC as a serious threat, are increasing, and Candida auris alone was recently added as an urgent threat. Echinocandins are guideline-preferred for the treatment of invasive candidiasis due to in vitro potency, a favorable toxicity profile, and convenient dosing. The purpose of this study was to perform a pharmacoepidemiologic analysis on patterns of echinocandin use at a large, quaternary care medical center. Methods Data reporting echinocandin use, pharmacy data, and clinical microbiologic data obtained from 2017–19 were pooled. Monthly days of therapy (DOT) per 1,000 patient days were calculated during the study period along with number of unique orders. Investigators evaluated the proportion of echinocandin-treated patients with or without positive Candida cultures; the relationship between echinocandin use and hospital admission and discharge dates was also evaluated. Results Echinocandin monthly DOT/1,000 patient days present averaged 26 (± 5) DOT and did not change appreciably during the study period. Of the patients with microbiologic evidence of Candida, 842 (51%) received echinocandin courses. Length of echinocandin therapy was significantly longer for patients with positive Candida cultures (5.5 ± 5.9 days) compared to those without positive cultures (3.9 ± 5.0 days; p< 0.001). Of 1,659 echinocandin courses evaluated, 549 courses (33%) were initiated within 2 days of hospital admission and the average time from hospital admission to echinocandin start was 9 (± 13) days. A total of 505 (24%) echinocandin courses were continued until the day of discharge. Conclusion The rate of echinocandin use did not change appreciably during the study period. A significant proportion of echinocandin courses were either started upon hospital admission or were continued until the day of discharge. Further studies to evaluate antifungal stewardship opportunities for the echinocandin pharmacologic class are warranted. Disclosures Nicholas D. Beyda, PharmD, BCPS, Astellas (Advisor or Review Panel member)Cidara (Grant/Research Support, Scientific Research Study Investigator) Kevin W. Garey, PharMD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator)

scholarly journals 9. Evaluation of Synergy Testing Methods for Clinical Labs to Determine Susceptibility of Extensively Drug-resistant Gram-negatives to Ceftazidime/ Avibactam and Aztreonam Combination Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S5-S6
Author(s):  
Ayesha Khan ◽  
Samuel G Erickson ◽  
Cedric H Pettaway ◽  
Cesar A Arias ◽  
William R Miller ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Clinical Decision Making ◽  
Research Study ◽  
Scientific Research ◽  
Major Error ◽  
Testing Methods ◽  
Research Support ◽  
Testing Method ◽  
Study Investigator ◽  
Synergy Testing

Abstract Background Carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CR-PA) producing Metallo-β-lactamases (MBLs) cause severe nosocomial infections with no defined treatment. Combination therapy with ceftazidime/ avibactam (CZA) and aztreonam (ATM) is a potential option, but there is no approved, feasible, synergy testing method for clinical labs to guide clinical decision making. Here, we evaluate the performance of 4 synergy testing methods using gradient-strips or disks. Methods We used 10 representative Enterobacterales strains, namely, E. coli, K. pneumoniae, and E. cloacea, and 6 PA strains harboring MBL, GES or non-MBL enzymes (Fig 1). 4 strains were successfully treated with CZA-ATM in case reports, the rest were from the CDC AR Bank. Four synergy testing methods were evaluated, i) Disk stack (DS), ii) Disk elution (DE), iii) Gradient-strip Stack (SS), iv) Gradient-strip Cross (SX) (Fig 1). All methods were run side-by-side as per CLSI guidelines with broth microdilution (BMD) as the reference. Data is the mean of 3 replicates. Synergy is defined as a strain that is resistant (R) to ATM but drops to ≤ the susceptible (S) breakpoint (Table 1) in the presence of CZA (Fig 2). Categorical agreement (CA), very major error (VME), major error (ME), minor error (MI) were calculated across methods for CZA-ATM synergy relative to BMD. Summary of synergy testing methods evaluated CLSI Breakpoints used for this study Results All CRE with NDM and PA with GES were ATM-R, CZA-R and S to the CZA-ATM combination. PA with NDM or VIM remained R to CZA-ATM likely due to other mechanisms of resistance. CA was high for DE (100%), SS (81%, MI 19%), and SX (88%, MI 13%) but low for DS (25%, ME 54%, MI 31%). Representative strains are shown (Fig 2, Table 2). Removing PA, CA for DE, SS, and SX was 100% and 20% for DS. Representative results of strains with each synergy testing method. Representative data of strains displaying synergy (green) or no synergy (red) Conclusion Overall, DE was the most reliable method for CZA-ATM synergy testing, and could be a valuable tool in low-resource labs. SS and SX were reliable but prone to technical error. DS had the worst performance. Disks and gradient-strips had identical performance across brands. We propose an algorithm for ATM-R, CZA-R, and MBL-positive CRE, where CZA-ATM synergy testing may be beneficial to guide therapy. These methods are reliable qualitative indicators of the presence or absence of synergy. Synergy testing is not recommended for CR-PA due to complex resistance profiles. Disclosures Cesar A. Arias, M.D., MSc, Ph.D., FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support) William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member)

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