scholarly journals 1185. Oseltamivir Prescribing Patterns for Infants with Influenza and Factors Associated with Guideline Adherence

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S684-S684
Author(s):  
Haniah A Zaheer ◽  
Sarah Chamseddine ◽  
Hui Liu ◽  
John V Williams ◽  
Judith M Martin ◽  
...  
Keyword(s):  
High Risk ◽  
Guideline Adherence ◽  
Treatment Guidelines ◽  
Data Monitoring Committee ◽  
Panel Member ◽  
Prescribing Patterns ◽  
Urgent Care ◽  
Review Panel ◽  
Factors Associated ◽  
Contact Points

Abstract Background The Centers for Disease Control and Prevention (CDC) recommends oseltamivir be given to children < 2 years old with confirmed or suspected influenza as they are at high risk for complications. We sought to analyze oseltamivir prescribing patterns and to describe factors associated with adherence and non-adherence to CDC guidelines. Methods We used a retrospective cohort of infants ≤ 12 months old born from January 1, 2011 to December 31, 2019 within the University of Pittsburgh Medical Center health system in Southwestern Pennsylvania and who had ≥ 2 well-child visits during their first year. Infants with laboratory-confirmed influenza from January 1, 2011 to April 30, 2020 were included. Electronic health records were reviewed to describe oseltamivir prescriptions and influenza-related characteristics. Factors associated with adherence and non-adherence to CDC influenza treatment guidelines were assessed with univariate logistic regression. Results Of 422 infants with laboratory-confirmed influenza, 86% were prescribed oseltamivir. The proportion of infants prescribed oseltamivir increased from an average of 63% during 2011-2016 to 90% during 2016-2020 (OR:5.2; 95%CI: 2.9-9.5). 96% of prescriptions instructed twice daily dosing, 2% had once daily, and 2% were unknown frequency. 91% of prescriptions were for 5 days, 7% had no duration, and 2% were for > 5 days. Infants ≥ 6 months of age compared to < 6 months were less likely to be prescribed oseltamivir (83.3% vs. 100%; p< 0.001); tested for influenza in the emergency room/urgent care (OR: 0.3; 95%CI: 0.2-0.6), or admitted to the hospital (OR:0.5; 95%CI:0.2-0.9). Infants were more likely to be treated with oseltamivir if they had a known influenza positive contact (OR:2.3; 95%CI:1.0-5.2) or had fever ≥ 38.0C (OR:2.0; 95%CI:1.2-3.5). There was no difference in prescribing practices based on history of prematurity or chronic medical conditions. Conclusion Adherence to CDC influenza treatment guidelines for infants is high and has improved over time. However, targeted education at high-risk contact points may further improve guideline adherence. Disclosures John V. Williams, MD, GlaxoSmithKline (Advisor or Review Panel member, Independent Data Monitoring Committee)Quidel (Advisor or Review Panel member, Scientific Advisory Board) Judith M. Martin, MD, Merck Sharp and Dohme (Consultant)

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 LB2. Safety and Efficacy of Combination SARS-CoV-2 Monoclonal Neutralizing Antibodies (mAb) BRII-196 and BRII-198 in Non-Hospitalized COVID-19 Patients

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S807-S808
Author(s):  
Teresa H Evering ◽  
Mark Giganti ◽  
Kara W Chew ◽  
Michael Hughes ◽  
Carlee Moser ◽  
...  
Keyword(s):  
High Risk ◽  
Symptom Onset ◽  
Interim Analysis ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Panel Member ◽  
The Philippines ◽  
Research Support ◽  
Review Panel ◽  
Research Grant

Abstract Background SARS-CoV-2 continues to spread and the development of safe and effective therapeutics for the prevention of severe disease remains a priority. BRII-196 and BRII-198 are non-competing anti-SARS-CoV-2 mAbs with YTE triple amino acid substitution in Fc to extend half-life and reduce receptor binding, that are being studied for treatment of COVID-19 in the ACTIV-2 Trial, sponsored by NIAID and led by ACTG. Methods ACTIV-2 evaluates safety/efficacy of investigational agents for treatment of non-hospitalized adults with mild-moderate COVID-19 under a randomized, blinded, controlled adaptive platform. BRII-196/BRII-198 (1000 mg each) as a single dose given as sequential infusions, or placebo to those at high risk of clinical progression (i.e., age ≥ 60 years or presence of other medical conditions) within 10 days of symptom onset and positive test for SARS-CoV-2. The primary endpoint was hospitalization and/or death through day 28. We report Phase 3 BRII-196/BRII-198 trial results per DSMB recommendation following an interim analysis. Results Between January and July 2021, 837 participants (418 active, 419 placebo) from sites in the US (66%), Brazil, South Africa, Mexico, Argentina and the Philippines were randomized and received study product at time of emerging variants. Median age 49 years (Q1, Q3: 39, 58), 51% female, 17% Black/African-American and 49% Hispanic/Latino, with median 6 days from symptom onset. At interim analysis 71% and 97% had a day 28 and 7 visit, respectively. For all available data at interim review, BRII-196/BRII-198 compared to placebo had fewer hospitalizations (12 vs. 45) and deaths (1 vs. 9). At day 28 of follow-up, there was an estimated 78% reduction in hospitalization and/or death (2.4 vs. 11.1%), relative risk 0.22 (95% CI: 0.05, 0.86), P=0.00001 (nominal one-sided). Grade 3 or higher adverse events (AEs) were observed less frequently among BRII-196/BRII-198 participants than placebo (3.8% vs. 13.4%) with no severe infusion reactions or drug related serious AEs. Conclusion BRII-196/BRII-198 was safe, well-tolerated, and demonstrated significant reduction compared to placebo in the risk of hospitalization and/or death among adults with mild-moderate COVID-19 at high risk for progression to severe disease. Disclosures Kara W. Chew, MD, MS, Amgen (Individual(s) Involved: Self): Grant/Research Support; Merck Sharp & Dohme (Individual(s) Involved: Self): Grant/Research Support David Alain Wohl, MD, Gilead Sciences (Individual(s) Involved: Self): Advisor or Review Panel member, Consultant, Research Grant or Support, Scientific Research Study Investigator; Janssen (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support; ViiV (Individual(s) Involved: Self): Advisor or Review Panel member, Research Grant or Support Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV (Consultant, Research Grant or Support) David A. Margolis, MD MPH, Brii Biosciences (Employee) Courtney Fletcher, Pharm.D., National Institute of Allergy and Infectious Diseases, NIH (Grant/Research Support) Davey Smith, M.D., Linear Therapies, Matrix Biomed, Bayer (Consultant, Shareholder) Eric Daar, Gilead (Consultant, Grant/Research Support)Merck (Consultant)ViiV (Consultant, Grant/Research Support)

scholarly journals 951. Weight Gain Associated With Antiretroviral Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S508-S508
Author(s):  
Yesha Patel ◽  
Sheila Okere ◽  
Mark Lustberg ◽  
Carlos Malvestutto
Keyword(s):  
Human Immunodeficiency Virus ◽  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Weight Change ◽  
Panel Member ◽  
Male Gender ◽  
Review Panel ◽  
Factors Associated ◽  
Immunodeficiency Virus

Abstract Background Obesity is a global public health crisis with a growing prevalence in persons with human immunodeficiency virus (PWH) population. In this study, we aimed to investigate factors associated with weight gain in the PWH population. Methods This was a single-centered, retrospective cohort study of our clinic patient population from January 1, 2015 to January 1, 2019. Patients with human immunodeficiency virus (HIV) were identified from the electronic health record and a randomized sample of 300 patients who had at least two follow up appointments, were on antiretroviral therapy, and had viral loads less than 200 were evaluated. The primary outcome was weight change over follow up. Cox Proportional Hazards models were used, taking a weight gain > 3 kg as the outcome, and the time on therapy between visits as the time to event. Robust linear regression was used to model mean changes in weight, accounting for influential observations. All analysis were performed in STATA 16.0. Table 1 Results At baseline, 87% were male, 63% were white, and 65% were overweight/obese. 30% were on a protease inhibitor, 46% were on non-nucleoside reverse transcriptase inhibitor, and 37% were on an integrase inhibitor. 64% were on Tenofovir disoproxil (TDF), 8% were on Tenofovir alafenamide (TAF), and 19% were on Abacavir. Mean weight change over follow up was significantly increased at 1.31 kg (95% CI = 0.58 – 2.04 kg, p= 0.0004). TAF use and male gender were significantly associated with risk of weight gain > 3 kg in univariate analysis [respectively, OR = 2.53, 95% CI = 1.30 – 4.92, p = 0.006; OR = 2.60, 95% CI = 1.05 – 6.45, p = 0.04]. In multivariate analysis, TAF use was significantly associated with weight gain > 3 kg, while male gender was of borderline significance [respectively, OR = 2.29, 95% CI = 1.17 – 4.47, p = 0.01; OR = 2.40, 95% CI = 0.96 – 5.97, p=0.060]. Significant factors associated with weight change are noted in Table 1. Conclusion As PWH are living longer on effective ARV therapy, monitoring for weight gain is required as obesity contributes to morbidity and mortality from cardiovascular disease and metabolic diseases. Key factors for weight gain in our clinic population include male gender, baseline diagnosis of hypertension, use of TAF, bictegravir use, and rilpivirine use. Disclosures Carlos Malvestutto, MD, Gilead Sciences (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member)

scholarly journals 1499. Incidence of Community Acquired Pneumonia by Age and Comorbid Conditions in the Veterans Health Administration (VHA)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S751-S752
Author(s):  
Taissa A Bej ◽  
Sunah Song ◽  
Brigid Wilson ◽  
Richard Banks ◽  
Janet Briggs ◽  
...  
Keyword(s):  
At Risk ◽  
High Risk ◽  
Panel Member ◽  
Community Acquired Pneumonia ◽  
Comorbid Conditions ◽  
Moderate Risk ◽  
Research Support ◽  
Review Panel ◽  
Risk Condition ◽  
Research Grant

Abstract Background Community acquired pneumonia (CAP) remains a major cause of morbidity and mortality. Risk factors for CAP are often grouped as moderate- (e.g., diabetes mellitus, chronic liver, lung, or heart disease) and high-risk (e.g., immunosuppressive) conditions, which in turn influences preventative strategies, notably pneumococcal vaccination. Here, we use the national VHA databases to assess the risk of CAP among adults, expanding on previous work by using administrative data to assess the incidence of CAP among people with > 1 moderate risk condition Methods We used the national VHA databases merged with claims summaries from the Centers for Medicare and Medicaid Services (CMS) to identify patients receiving clinical care in the VHA without clinical Medicare claims in 2016-2017. Within this population, we identified CAP cases defined by the presence of a diagnostic code for pneumonia, chest X-ray, and antibiotics as well as the absence of healthcare exposure or antibiotics in prior 90 days. We determined the total patient years at risk and calculated incidence rates by age group and by moderate- and high-risk comorbid conditions. Results We identified 37,348 CAP cases in 7.9 million person-years at risk and observed similar annual rates in 2016 and 2017 (468.9 and 472.2 cases/100,000 person-years, respectively). The prevalence of high-risk conditions and incidence of CAP increased with age whereas the prevalence of >1 moderate-risk condition peaked for ages 50-64 and 65-74 years (Table). The incidence of CAP among those with > 1 moderate-risk condition exceeded that of patients with high-risk conditions across all age strata (Figure). Table Figure Conclusion Age-adjusted analysis revealed that the greatest burden of CAP occurs in patients with > 1 moderate-risk condition, even compared to those with a high-risk condition. Our analysis of CAP based on national VHA data suggest that additional preventative health measures directed at individuals older than 50 years with > 1 moderate-risk condition may help to reduce the burden of CAP and limit its morbidity and mortality. Disclosures Robin Jump, MD, PhD, Accelerate (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member) Federico Perez, MD, MS, Accelerate (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals Adherence to Stage-Specific Treatment Guidelines for Patients With Colon Cancer

2012 ◽  
Vol 30 (9) ◽  
pp. 972-979 ◽  
Author(s):  
Ryaz Chagpar ◽  
Yan Xing ◽  
Yi-Ju Chiang ◽  
Barry W. Feig ◽  
George J. Chang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Treatment Guidelines ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Disease Stage ◽  
Nccn Guidelines ◽  
Factors Associated ◽  
The Impact

Purpose Adherence to evidence-based treatment guidelines has been proposed as a measure of cancer care quality. We sought to determine rates of and factors associated with adherence to the National Comprehensive Cancer Network (NCCN) treatment guidelines for colon cancer. Patients and Methods Patients within the National Cancer Data Base treated for colon adenocarcinoma (2003 to 2007) were identified. Adherence to stage-specific NCCN guidelines was determined based on disease stage. Hierarchical regression analyses were performed to identify factors predictive of adherence, overtreatment, and undertreatment. Results A total of 173,243 patients were included in the final cohort, 123,953 (71%) of whom were treated according to NCCN guidelines. Patients with stage I disease were more likely to receive guideline-based treatment (96%) than patients with stage II (low risk, 66%; high risk, 36%), III (71%), or IV (73%) disease (P < .001). Adherence to consensus-based guidelines increased over time. Factors associated with adherence across all stages included age, Charlson-Deyo comorbidity index score, later year of diagnosis, and insurance status. Among patients with high-risk stage II or stage III disease, older patients with pre-existing comorbidities and patients with lower socioeconomic status were less likely to be offered adjuvant chemotherapy. Among patients with stage I and II disease, young, healthy patients were more likely to be recommended chemotherapy, in discordance with NCCN guidelines. Conclusion Significant variation exists in the treatment of colon cancer, particularly in treatment of high-risk stage II and stage III disease. The impact of nonadherence to guidelines on patient outcomes needs to be further elucidated.

scholarly journals 1399. Clarithromycin–Rifampin-based Treatment for Non-tuberculous Mycobacterial Infections in Immunocompromised Patients Who Require Concomitant CYP-Metabolized Medications

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S784-S784
Author(s):  
Isabel H Gonzalez-Bocco ◽  
Muneerah M Aleissa ◽  
Matthew Cheng ◽  
Jennifer Manne-Goehler ◽  
Francisco M Marty
Keyword(s):  
Adverse Events ◽  
Treatment Guidelines ◽  
Panel Member ◽  
Positive Culture ◽  
Good Alternative ◽  
Drug Regimen ◽  
Current Treatment ◽  
Review Panel ◽  
Cyp Induction ◽  
Immunocompromised Hosts

Abstract Background Non-tuberculous mycobacteria (NTM) are causes of pulmonary and extrapulmonary disease that frequently affect immunocompromised hosts (ICH). Current treatment guidelines recommend a macrolide-based, multi-drug regimen that includes rifampin. Rifampin is a potent cytochrome P450 (CYP) 3A inducer, which often results in drug-drug interactions in ICH receiving multiple CYP substrates. One way to mitigate rifampin’s CYP induction is to utilize clarithromycin, a CYP inhibitor, as the accompanying macrolide. We evaluated the incidence of NTM treatment-related adverse events (AEs) in patients who received a clarithromycin-based regimen compared to patients who received an azithromycin-based regimen. Methods We conducted a retrospective review of NTM infection in 30 immunocompromised adults. All participants had a positive culture for a NTM and had received a rifamycin (rifampin or rifabutin) with a macrolide (azithromycin or clarithromycin) for treatment at Brigham and Women’s Hospital between 01/01/2011-10/18/2020 or Dana-Farber Cancer Institute between 06/03/2015-07/01/2020. The primary outcome was the incidence of NTM treatment-related AEs in patients who received a clarithromycin-based regimen compared to those who received an azithromycin-based regimen. Results There were no significant differences in the reasons for discontinuation of NTM treatment or 90-day mortality between groups. The number of AEs possibly related to NTM treatment were similar in patients who received a clarithromycin-based regimen and those who received an azithromycin-based one (10/13 vs. 14/17; p=0.73). The most common AE was liver function test abnormalities (Table 1). Additionally, the proportion of patients requiring dose adjustments for interacting medications and patients with out-of-range tacrolimus levels were similar between the two groups (23.1% vs. 29.4%; p=0.76 and 8.0% vs. 6.0%; p=1.00, respectively). Table 1: Adverse events Conclusion A clarithromycin-based regimen for NTM treatment was safe and well tolerated in our patient population. This combination provides a good alternative for patients requiring medications that are CYP substrates, or those who cannot tolerate azithromycin. Disclosures Matthew Cheng, MD, GEn1E Lifesciences (Advisor or Review Panel member)Kanvas Biosciences (Board Member, Shareholder)nplex biosciences (Advisor or Review Panel member)

scholarly journals 1612. Evaluation of the Use of Ceftolozane/Tazobactam for the Treatment of ESBL-producing Enterobacterales Infections Using International Data from SPECTRA (Study of Prescribing Patterns and Effectiveness of Ceftolozane/Tazobactam Real World Analysis)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S800-S800
Author(s):  
Alex Soriano ◽  
Laura A Puzniak ◽  
Matteo Bassetti ◽  
Sundeep Kaul ◽  
Pamela Moise ◽  
...  
Keyword(s):  
Clinical Success ◽  
Panel Member ◽  
Empiric Therapy ◽  
Prescribing Patterns ◽  
Research Support ◽  
Review Panel ◽  
Patient Database ◽  
Severe Infections ◽  
Immunocompromised Hosts

Abstract Background There is a paucity of data on outcomes of patients with severe ESBL-producing Enterobacterales infections treated with empiric or directed ceftolozane/tazobactam (C/T). This study looked at the treatment patterns and outcomes associated with C/T use in the treatment of ESBL-producing Enterobacterales. Methods Data were collected from an international cohort of 32 hospitals in 6 countries as part of SPECTRA, a retrospective multicenter database of C/T use globally, from 2016 – 2019. All adult patients with an ESBL positive Enterobacterales sterile site culture and treated with ≥ 48 hours of C/T were eligible. Outcomes assessed were clinical success, 30-day mortality from index event and readmission. Results There were 59 patients with 121 ESBL positive isolates. Blood and urine were the most common sites of infection at 19.8% each, followed by respiratory (18.2%). E. coli (50%) and K. pneumoniae (30%) were the most common pathogens. On average patients had 2 positive ESBL isolates; median 1; range 1-15. Most patients had the same infection site and ESBL pathogen, however 13 had multi-site ESBL pathogens identified and only 2 had polymicrobial ESBL pathogens. Septic shock was observed in 14 (24%) patients; 29 (49%) were in the ICU at the onset of infection. The most common comorbid conditions were immunocompromised hosts (37%) and cardiac disease (32%). 29% of patients were transplant recipients, and 28% had a CrCl &lt; 50 ml/min. In most patients (71%), C/T was given as directed therapy (i.e., once culture results were available). C/T was given prior to culture results (i.e., as empiric therapy) in 17 (29%) patients, of which 77% had clinical success. C/T dose was 1.5 g in 49%. Only 2 of 10 patients with a respiratory source received the currently licensed 3 g dose. Overall, clinical success was observed in 36 (61%) patients. 30-day mortality was 12%. Readmissions occurred in 5%, of which 2 were infection related. Conclusion The role of newer non-carbapenem antibiotics in the treatment of severe ESBL infections is currently undefined. In a multinational patient database, C/T was found to be effective in severe infections caused by ESBL-producing Enterobacterales. Prospective studies are needed to further define the role of C/T in the setting of frequent drug-resistant Gram-negative pathogens. Disclosures Laura A. Puzniak, PhD, Merck (Employee) Matteo Bassetti, MD, Shionogi Inc. (Advisor or Review Panel member) Pamela Moise, PharmD, Merck & Co., Inc. (Employee, Shareholder) David Paterson, Accelerate (Speaker’s Bureau)BioMerieux (Speaker’s Bureau)BioMerieux (Advisor or Review Panel member)Entasis (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Merck (Grant/Research Support)Merck (Speaker’s Bureau)Pfizer (Speaker’s Bureau)Shionogi & Co., Ltd. (Grant/Research Support)VenatoRx (Advisor or Review Panel member)

scholarly journals 1066. Immune Escape Mutant Detection Using Commercially Available Methods for Hepatitis B Surface Antigen Serological Testing

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S562-S562
Author(s):  
Robert Gish ◽  
Vincent Streva
Keyword(s):  
Hepatitis B ◽  
Immune Escape ◽  
Hepatitis B Surface Antigen ◽  
Panel Member ◽  
The United States ◽  
Hbv Infection ◽  
Hepatitis B Vaccination ◽  
Review Panel ◽  
B Virus ◽  
Escape Mutants

Abstract Background Although overall infection rates of Hepatitis B virus (HBV) in the United States (US) remain stable, as many as 2.2 million persons are still chronically infected with Hepatitis B Virus (HBV)1. Persons who inject drugs (PWID) are at a higher risk of HBV infection and since 2009 three states (KY, TN, WV) have reported up to a 114% increase in cases of acute HBV infection due to higher infection rates among a non-Hispanic white populations (30–39 years), and injection drug users2. Hepatitis B vaccination is recommended as primary prevention for adults who are at increased risk for HBV infection, including PWID. However, data from the National Health Interview Survey indicate that hepatitis B vaccination coverage is low among adults in the general population3, and it is likely to be lower among injection drug users. Hepatitis B Surface Antigen (HBsAg) is the first serological marker to appear after HBV exposure and infection; this marker is included in the recommended panel for acute hepatitis diagnosis and accurate detection is necessary for early and accurate diagnosis. Serological testing challenges exist for HBsAg due to the high degree of genetic variability which can further be exacerbated by endogenous and exogenous pressures. The immuno-dominant region may have one or more mutations described as immune escape mutations which can decrease or abrogate HBsAg binding to antibodies used in immunoassays. Although the prevalence of these mutations is not well documented in the United States, international studies have shown that up to 79% of HBV-reactivated patients (vs 3.1% of control patients; p&lt; 0.001) carry HBsAg mutations localized in immune-active HBsAg regions4. Methods A study was conducted using a panel of 10 unique recombinant HBsAg immune escape mutants. Panel members were tested by commercially available HBsAg serological immunoassays. Results It was found that although commercially available HBsAg immunoassays are the primary diagnostic tool for HBV diagnosis, not all HBsAg immune escape mutants are detected, with some method detecting as few as 5 out of 10 of these mutant samples. Figure 1 Conclusion Improvement is needed in commercially available methods for the accurate detection of HBsAg. Disclosures Robert Gish, MD, Abbott (Consultant)AbbVie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)Access Biologicals (Consultant)Antios (Consultant)Arrowhead (Consultant)Bayer (Consultant, Speaker’s Bureau)Bristol Myers (Consultant, Speaker’s Bureau)Dova (Consultant, Speaker’s Bureau)Dynavax (Consultant)Eiger (Consultant, Advisor or Review Panel member)Eisai (Consultant, Speaker’s Bureau)Enyo (Consultant)eStudySite (Consultant, Advisor or Review Panel member)Exelixis (Consultant)Fujifilm/Wako (Consultant)Genentech (Consultant)Genlantis (Consultant)Gilead (Consultant, Advisor or Review Panel member, Speaker’s Bureau)GLG (Consultant)HepaTX (Consultant, Advisor or Review Panel member)HepQuant (Consultant, Advisor or Review Panel member)Intercept (Consultant, Speaker’s Bureau)Ionis (Consultant)Janssen (Consultant)Laboratory for Advanced Medicine (Consultant)Lilly (Consultant)Merck (Consultant)Salix (Consultant, Speaker’s Bureau)Shionogi (Consultant, Speaker’s Bureau)Viking (Consultant)

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