912. Expansion of Hepatitis C Treatment with New Medicaid Subscription Model in Louisiana

Abstract Background It is estimated that nearly 80,000 people with hepatitis C are living in Louisiana, many with Medicaid coverage. Previously, only Medicaid patients free from drugs and alcohol with a fibrosis score of F3 or F4 were eligible for treatment, resulting in few patients receiving treatment. Beginning in July 2019, generic sofosbuvir/velpatasvir was made available through the Medicaid program in a subscription model, allowing unlimited hepatitis C treatment in Louisiana’s Medicaid program for 5 years at a set price to the program. This has dramatically expanded access to Hepatitis C treatment for people with Medicaid in Louisiana. Methods Patients with Hepatitis C seen in the Infectious Diseases Center at University Medical Center in New Orleans, in 2020 by the 5 main hepatitis C providers were included. Demographics and laboratory data were collected to determine outcomes. Results Most patients with a hepatitis C (HCV) viral load and insurance data had Medicaid (80%, N=275). Twenty-two (8%) were HIV co-infected. Most were men (75%) and African-American (77%). Among the mono-infected patients with Medicaid and an HCV viral load, 216 (85%) had an undetectable viral load by the beginning of June 2021. Of the remaining 37 patients, 30 patients were prescribed treatment; but did not take it (n=4), didn’t follow-up (n=23), or followed-up but never got labs (n=3). One was treated but had a treatment failure (n=1). Six of the 37 were not prescribed medications due to a short life expectancy or significant drug interactions. The percentage of patients with an undetectable viral load was similar by gender and race, however younger age groups had lower viral suppression. In those aged less than 35, only 47% had an undetectable viral load and among those aged 36 to 44, it was 66%. Using the previous criteria of requiring a fibrosis score of F3 or F4, only 20% (n=44) would have been eligible for medicine to treat hepatitis C. Conclusion The new hepatitis C treatment subscription model with resultant removal of previous barriers has dramatically expanded treatment for people with Medicaid in Louisiana. More than five times the number of Medicaid patients received treatment in 2020 in our academic medical clinic. Disclosures Yussef Bennani, MD, MPH, Gilead Sciences (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator)

Download Full-text

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.747 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S376-S376

Author(s):

Saki Ikeda ◽

Eduardo Benzi ◽

Lisa Hensch ◽

Sridevi Devaraj ◽

Shiu-Ki Rocky Hui ◽

...

Keyword(s):

Pediatric Patients ◽

Research Study ◽

High Titer ◽

Serum Antibody ◽

Laboratory Data ◽

Scientific Research ◽

Published Data ◽

Material Support ◽

Study Investigator ◽

Antibody Levels

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

Download Full-text

946. Risk factors and Metabolic Implications of Integrase Inhibitor Associated Weight Gain

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1132 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S505-S506

Author(s):

Archana Asundi ◽

Alex Olson ◽

Wenqing Jiang ◽

Swati Patel ◽

Laura F White ◽

...

Keyword(s):

Risk Factors ◽

Weight Gain ◽

Weight Change ◽

Research Study ◽

Laboratory Data ◽

Scientific Research ◽

Fiscal Year ◽

Secondary Outcome ◽

Art Initiation ◽

Study Investigator

Abstract Background Excessive weight gain associated with integrase strand transfer inhibitor (InSTI) antiretrovirals is an emerging issue in the current antiretroviral treatment (ART) era. Despite the known association between excess weight and impaired glucose tolerance in the general population, the metabolic implications of InSTI-associated weight gain have not been established. The objective of this study was to evaluate the presence of InSTI-associated weight gain amongst a diverse, urban population and to investigate potential risk factors and metabolic implications. Methods We obtained demographic, pharmacy and laboratory data from the hospital clinical data warehouse for ART-naïve adult HIV+ patients at Boston Medical Center between fiscal year (FY) 2007-2017. We compared patients who initiated on an InSTI to those with an alternate regimen (i.e. PI, NNRTI) who remained on their initial regimen for at least 18 months. Individuals with diabetes mellitus (DM) prescription or ICD 9/10 code prior to ART initiation were excluded. Our primary outcome was percent weight change in the first 24 months of ART estimated by linear mixed effects model fit by restricted maximum likelihood. Our secondary outcome was incident DM diagnosis in the 18 months after ART using progression-free survival (PFS). PFS rates were estimated by the Kaplan-Meier method and log-rank test, and Cox proportional-hazards model were determined, all using R v3.6.2. Results Between FY 2007-2017, 139 patients were initiated on InSTIs and 1117 were initiated on alternative anchor regimens. Approximately, one third of the cohort was female and more than 75% were non-white. InSTI use in women was associated with increased weight gain in the first 24 months of ART compared to non-InSTIs (+9.57%, p = 0.002, Figure 1). InSTI use was associated with more incident DM diagnoses in the first 18 months of ART compared to non-InSTI regimens (HR = 3.27, p = 0.014). Figure 1: Percentage weight change from baseline at ART initiation between InSTI and non-InSTI regimens Conclusion Females have higher InSTI-associated weight gain which suggests they may be more susceptible to adverse metabolic issues. InSTI use appears to be associated with an increased incidence of DM diagnoses following ART initiation. Further prospective and controlled studies will be necessary to describe the mechanism of this effect and refine HIV management strategies. Disclosures Archana Asundi, MD, Gilead (Scientific Research Study Investigator)Merck (Scientific Research Study Investigator)ViiV (Scientific Research Study Investigator) Nina H. Lin, MD, Gilead Sciences (Scientific Research Study Investigator)ViiV (Scientific Research Study Investigator)

Download Full-text

525. Atovaquone for Treatment of COVID-19 (Ataq COVID-19) Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.724 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S363-S364

Author(s):

Mamta K Jain ◽

Hesham Sadek ◽

James de Lemos ◽

Darren mcGuire ◽

...

Keyword(s):

Viral Load ◽

Viral Replication ◽

Research Study ◽

Scientific Research ◽

Standard Of Care ◽

Additional Analysis ◽

Study Investigator ◽

Standard Of Care Treatment ◽

Over Time

Abstract Background Our group performed an in-silico screen to identify FDA approved drugs that inhibit SARS-C0V-2 main protease (Mpro), followed by in vitro viral replication assays, and in vivo pharmacokinetic studies in mice. These studies identified atovaquone as a promising candidate for inhibiting viral replication. Methods Enrolled patients were randomized in a 2:1 fashion to atovaquone 1500 mg twice daily versus matched placebo. Patients received standard of care treatment including remdesivir, dexamethasone, or convalescent plasma as deemed necessary by the treating team. Patients agreed to allow collection of saliva at baseline and twice a day while hospitalized or up to 10 days. Saliva was collected and RNA extracted for viral load (VL) measurement by Real-time PCR. Our primary outcome was to examine the between group differences in log transformed VL(copies/mL) using generalized linear mixed-effect models of repeated measures from all samples. Additional analysis of Atovquone plasma concentrations were examined and correlated with viral load and body mass index (BMI). Results Of the 61 patients enrolled; 41 were received atovaquone and 19 placebo. Overall the population was predominately male Hispanic with a mean age of 51 years. The two groups were balanced (Table 1) with regard to age, gender, race, co-morbidities, days from onset of symptoms, baseline oxygen requirements, and receipt of COVID-19 specific standard of care treatment. A higher proportion with diabetes was noted in the Atovaquone arm. The log10 VL was 5.25 copies/mL vs. 4.79 copies/mL at baseline in the atovaquone vs. placebo group. Although there was a decrease in VL over time, there was no differences between the atovaquone plus standard of care arm versus the standard of care arm (Figure 1). Additional analysis of atovaquone plasma concentration demonstrated a wide variation in atovaquone levels, inverse association between atovaquone levels and BMI (rho -0.44, p=0.03), and Day 5 concentrations and VL (rho -0.54, p=0.005). Figure 1. Mean viral load of COVID-19 over time of atovaquone (blue) vs. placebo (red). Table 1. Baseline characteristics Conclusion Although atovaquone showed promising in vitro antiviral properties for COVID-19, in this pilot study we did not detect a change in VL in patients who received atovaquone compared to placebo, possibly due to failure of patients achieve adequate drug levels. Disclosures Mamta K. Jain, MD, MPH, Gilead Sciences Inc. (Individual(s) Involved: Self): Research Grant or Support, Scientific Research Study Investigator; GlaxoSmithKline (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Scientific Research Study Investigator; Vasgene (Individual(s) Involved: Self): Scientific Research Study Investigator

Download Full-text

686. Elevations in TNFα and IL-18 are Associated with Increased Risk of Probable Cytomegalovirus Tissue Invasive Disease in Solid Organ Transplant Recipients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.878 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S396-S397

Author(s):

Andrew H Karaba ◽

Alexis Figueroa ◽

Stuart C Ray ◽

Robin K Avery ◽

...

Keyword(s):

Viral Load ◽

Research Study ◽

Organ Transplant ◽

Scientific Research ◽

Principal Component ◽

Solid Organ Transplant ◽

Solid Organ ◽

Study Investigator ◽

Cmv Disease ◽

Cmv Dnaemia

Abstract Background Human cytomegalovirus (CMV) continues to cause significant morbidity and mortality in solid organ transplant (SOT) recipients despite prophylaxis. Tissue invasive CMV disease (TI-CMV) can lead to end-organ damage and graft loss. Diagnosing TI-CMV can be challenging as CMV viral load in the blood does not always correlate with episodes of TI-CMV and therefore definitive diagnosis often requires an invasive procedure such as bronchoscopy or colonoscopy. The purpose of this study was to determine if proinflammatory cytokines, including IL-18, are elevated in SOT recipients with probably TI-CMV as a way to identify patients at risk for this severe form of CMV disease. Methods The electronic medical record was searched for adult SOT recipients who were tested for CMV via blood qPCR during an 11-month period.Twenty-nine SOT recipients were identified that had episodes of CMV DNAemia without other concomitant infections during this time period. Patients were divided into those that had probable TI-CMV and those with CMV DNAemia alone, by chart review. Inflammatory cytokines (IFNγ, TNFα, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-18, and IL-1RA) were measured in residual plasma from these patients using a commercially available multiplex assay for at least two time points during the study period. Wilcoxon-Rank-Sum, logistic regression, and principal component analysis was performed comparing patients with and without probable TI-CMV. Results Patients with probable TI-CMV had significantly higher IL-18, TNFα, and IL-1β than patients with CMV DNAemia alone (p < 0.001, < 0.001, and < 0.05 respectively). When adjusting for transplant type and CMV recipient serostatus, elevations in TNFα (OR 1.43, 95% CI 1.07-1.92) and IL-18 (OR 2.00, 95% CI 1.06-3.75) were associated with increased odds of having probable TI-CMV. In principal component analysis the combination of CMV viral load, IL-18, TNFa, and IL-1β accounted for 80% of the variance in the data. Conclusion TNFα and IL-18 in combination with CMV viral load may be useful in predicting likelihood of TI-CMV. This is important in situations where tissue biopsies are not feasible, and adds to our diagnostic capability for TI-CMV in SOT recipients. Disclosures Stuart C. Ray, MD, miDiagnostics, Inc. (Board Member, Research Grant or Support) Robin K. Avery, MD, Aicuris (Scientific Research Study Investigator)Astellas (Scientific Research Study Investigator)Chimerix (Scientific Research Study Investigator)Merck (Grant/Research Support, Scientific Research Study Investigator)Oxford Immunotec (Scientific Research Study Investigator)Qiagen (Scientific Research Study Investigator)Takeda/Shire (Scientific Research Study Investigator)

Download Full-text

75. High Rates of Virologic Suppression with DTG/3TC in Newly Diagnosed Adults with HIV-1 Infection and Baseline Viral Load >500,000 c/mL: 48-Week Subgroup Analysis of the STAT Study

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.075 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S49-S49

Author(s):

Charlotte-Paige M Rolle ◽

Mezgebe Berhe ◽

Tulika Singh ◽

Roberto Ortiz ◽

Anson K Wurapa ◽

...

Keyword(s):

Viral Load ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Baseline Viral Load ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Hiv 1 ◽

Research Grant

Abstract Background The primary analysis of the STAT study demonstrated the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting through 24 weeks, with therapy adjustments for baseline resistance or hepatitis B virus (HBV) co-infection. Here we present secondary analyses through Week 48 of virologic outcomes in participants by baseline viral load (VL). Methods STAT is a single-arm study of treatment-naive adults with HIV-1 infection who initiated DTG/3TC ≤ 14 days after HIV-1 diagnosis without availability of screening/baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance < 30 mL/min/1.73 m2, then antiretroviral therapy (ART) was potentially adjusted and participants remained on study. Efficacy analyses included proportion of participants with HIV-1 RNA < 50 c/mL regardless of ART regimen at Week 48, among all participants (ITT-E missing = failure analysis) and among participants with available HIV-1 RNA data at Week 48 (observed analysis). Results Of 131 enrolled, DTG/3TC treatment was adjusted in 10 participants, and of those with available data (n=7), all (100%) achieved HIV-1 RNA < 50 c/mL at Week 48. At Week 48, 82% (107/131) of all participants (Figure 1) and 97% (107/110) of those with available data (Figure 2) achieved HIV-1 RNA < 50 c/mL. Of participants with baseline VL ≥ 500,000 c/mL, 89% (17/19) achieved HIV-1 RNA < 50 c/mL at Week 48; the remaining 2 withdrew from study. Of participants with baseline VL ≥ 1,000,000 c/mL, 90% (9/10) achieved HIV-1 RNA < 50 c/mL at Week 48 (Table); the remaining participant withdrew consent. Of the 17 participants with baseline VL ≥ 500,000 c/mL with available data through Week 48, 76% (13/17) achieved virologic suppression by Week 24. One participant with baseline VL ≥ 500,000 c/mL switched from DTG/3TC before the Week 48 assessment. Of the 9 participants with baseline VL ≥ 1,000,000 c/mL with available data through Week 48, most participants (8/9; 89%) were suppressed by Week 24. Figure 1. Virologic outcomes at Week 48, overall and by baseline VL and CD4+ cell count: ITT-E missing = failure analysis. Figure 2. Virologic outcomes at Week 48, overall and by baseline VL and CD4+ cell count: observed analysis. Table. Viral Load by Study Visit Among Participants with Baseline HIV-1 RNA ≥1,000,000 c/mL Conclusion These data provide evidence for the efficacy and feasibility of using DTG/3TC as a first-line regimen in a test-and-treat setting, including among participants with very high baseline VL. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Scientific Research Study Investigator, Advisor or Review Panel member)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau) Tulika Singh, MD MS AAHIVS, Gilead (Grant/Research Support, Advisor or Review Panel member)ViiV (Grant/Research Support, Advisor or Review Panel member, Speaker's Bureau) Moti Ramgopal, MD FIDSA, Abbvie (Scientific Research Study Investigator, Speaker's Bureau)Gilead (Consultant, Scientific Research Study Investigator, Speaker's Bureau)Janssen (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker's Bureau)Merck (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator, Speaker's Bureau) Dushyantha Jayaweera, MD, mrcog(uk), face, Gilead (Research Grant or Support)Janssen (Research Grant or Support)viiv (Research Grant or Support) Peter Leone, MD, viiv healthcare (Employee) Jessica Matthews, BS, ViiV Healthcare (Employee) Michael Cupo, Ph.D., GlaxoSmithKline (Employee) Mark Underwood, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Kostas Angelis, PhD, GSK (Employee, Shareholder) Brian Wynne, MD, ViiV Healthcare (Employee, Shareholder, I have shares in GSK, the part owner of ViiV) Deanna Merrill, PharmD, MBA, AAHIVP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Christopher T. Nguyen, MD, ViiV Healthcare (Employee) Jean A. van Wyk, MB,ChB, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Andrew Zolopa, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

Download Full-text

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1343 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S605-S605

Author(s):

Pierre Bulpa ◽

Galia Rahav ◽

Ilana Oren ◽

Mickaël Aoun ◽

George R Thompson ◽

...

Keyword(s):

Renal Function ◽

Renal Insufficiency ◽

Antifungal Agents ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Antifungal Treatment ◽

Successful Outcome ◽

Review Panel ◽

Study Investigator

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

Download Full-text

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1788 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S798-S799

Author(s):

Nicolo Cabrera ◽

Truc T Tran ◽

Travis J Carlson ◽

Faris Alnezary ◽

William R Miller ◽

...

Keyword(s):

Research Study ◽

Clinical Success ◽

Significant Proportion ◽

Scientific Research ◽

Panel Member ◽

Multidrug Resistant ◽

Outcome Data ◽

Research Support ◽

Gram Negative ◽

Study Investigator

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

Download Full-text

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1575 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S706-S706

Author(s):

Tanaz Petigara ◽

Ya-Ting Chen ◽

Zhiwen Liu ◽

Michelle Goveia ◽

David Johnson ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

The United States ◽

Vaccination Schedule ◽

Provider Type ◽

Factors Associated ◽

Study Investigator ◽

Region Of Residence ◽

Birth Dose ◽

To Receive

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

Download Full-text

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.866 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S391-S391

Author(s):

Maria M Traczewski ◽

Denise Beasley ◽

Amanda Harrington ◽

Sharon DesJarlais ◽

Omai Garner ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Reference Panel ◽

Broth Microdilution ◽

Salmonella Spp ◽

Research Personnel ◽

Gram Negative ◽

Material Support ◽

Study Investigator ◽

Support Research

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

Download Full-text

1400. Physician Attitudes towards Combination Vaccine Use in Infants up to 24 months of age in the United States (US)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1582 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S708-S709

Author(s):

Ya-Ting Chen ◽

Xinyi Ng ◽

Tanaz Petigara ◽

Jyoti Aggarwal ◽

Jenna Bhaloo ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Physician Attitudes ◽

Combination Vaccine ◽

Hexavalent Vaccine ◽

Family Practitioners ◽

Study Investigator ◽

Vaccine Schedule ◽

Combination Vaccines ◽

Number Of Injections

Abstract Background Combination vaccines reduce the number of injections and improve the timeliness of vaccination coverage. US Advisory Committee on Immunization Practices (ACIP) recommendations state that combination vaccines are generally preferred over equivalent individual component vaccines. Healthcare providers strongly influence parental decisions about vaccination. We sought a contemporary understanding of physician’s attitudes towards combination vaccine use in infants. Methods We conducted an online survey of US physicians (70 pediatricians and 30 family practitioners) who administer vaccines to infants aged 0-24 months and spend at least 2 days a week providing patient care. Information was collected on attitudes towards combination vaccines and factors that influence the choice of combination vaccine used in clinical practice. Descriptive analyses were performed. Results Physicians (mean age=50.2 years, range 30.0-70.0; 66% white; 37% women) reported a median of 4 injections (range 2-9) as the maximum that parents would accept at a single visit, and 71% routinely explained what combination vaccines are to parents. When deciding which pentavalent vaccine to use, physicians considered how the brand fits into the current vaccine schedule (71%); upfront purchase costs (64%); and availability as a prefilled syringe (61%). The main reasons for using combination vaccines were to reduce the number of injections (96%); ensure the infant is up-to-date with vaccinations (86%); and reduce the pain that the infant experiences with multiple injections (68%). More than half reported that their institution or practice has a program to incentivize infant vaccination according to schedule. If a hexavalent vaccine-based schedule was available, 76% of physicians said they would choose it over their current schedule comprising pentavalent or equivalent component vaccines. Conclusion Choice of pentavalent combination vaccine among pediatricians and family practitioners was largely dependent on convenience and cost-related factors. Over three-quarters would be inclined to use a hexavalent vaccine schedule if available. Disclosures Ya-Ting Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Xinyi Ng, PhD, Merck & Co., Inc. (Consultant) Tanaz Petigara, PhD, Merck & Co., Inc. (Employee, Shareholder) Jyoti Aggarwal, MHS, Merck & Co., Inc. (Consultant) Jenna Bhaloo, MPH, Merck & Co., Inc. (Consultant) Michelle Goveia, MD, Merck & Co., Inc (Employee, Shareholder) David Johnson, MD, MPH, Sanofi Pasteur (Employee, Shareholder) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)

Download Full-text