1298. Validation of Local Pseudomonas aeruginosa Risk Factors in Patients with Community-Onset Bacterial Pneumonia

Abstract Background Clinical guidelines for community-acquired pneumonia (CAP) encourage validation of local risk factors for multidrug-resistant organisms. This study aimed to validate previously derived, local risk factors for Pseudomonas aeruginosa in patients with community-onset bacterial pneumonia at Prisma Health-Midlands’ hospitals. Methods In this retrospective, observational cohort study, adult patients hospitalized with pneumonia MS-DRG codes from January 1, 2017 to March 31, 2020 were randomly screened. Enrolled subjects were admitted to 1 of 3 Prisma Health-Midlands’ hospitals with: diagnosis of pneumonia; receipt of inpatient antibiotics within 48 hours of symptom onset; receipt of over 48 hours of antibiotic therapy; and a causative bacterial pathogen identified via respiratory or blood culture, urinary antigen, or respiratory multiplex PCR panel. Performance of the locally derived score was compared to the Drug Resistance in Pneumonia (DRIP) Score, IDSA 2019 CAP guideline risk factors, and healthcare-associated pneumonia (HCAP) risk factors. Endpoints included sensitivity, specificity, positive and negative predictive value, overall accuracy, and over- and undertreatment rates. Overall accuracy was defined as a case in which the gram-negative antibiotic coverage recommended by the scoring schema would have been appropriate for the identified organism, i.e. neither overtreatment (overly broad-spectrum) nor undertreatment (inadequate spectrum). Results Of 713 patients screened, 36 patients met criteria and were enrolled. The most common bacterial pathogens identified were Pseudomonas aeruginosa (n = 10, 27.8%) and Streptococcus pneumoniae (n = 10, 27.8%). Performance characteristics for each scoring schema are summarized in Table 1. Table 1. Performance characteristics of risk scores predicting for Pseudomonas aeruginosa community-onset bacterial pneumonia. MDRO=multidrug-resistant organism; DRIP=Drug Resistance in Pneumonia Score; IDSA=Infectious Diseases Society of America 2019 Community-Acquired Pneumonia Guideline risk factors ; HCAP=healthcare-associated pneumonia risk factors Conclusion Compared to DRIP or IDSA 2019 CAP risk scores, the local risk score performed well at ruling out resistant gram-negatives given its higher specificity and lower overtreatment rate; yet, it did not perform as well at ruling in resistant gram-negatives given a lower sensitivity and undertreatment rate. All scores performed better than HCAP risk factors. Data from this study will be utilized to further refine the local risk score algorithm. Disclosures P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker’s Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member) Hana Winders, PharmD, BCIDP, biomerieux (Grant/Research Support) Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)Merck & Co. (Advisor or Review Panel member)Therapeutic Research Center (Speaker’s Bureau)Vaxart (Shareholder)

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1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1290 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S582-S583

Author(s):

Eleni Karantoni ◽

Yiqi Su ◽

Anat Stern ◽

Phaedon D Zavras ◽

Sergio Giralt ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

T Cell ◽

Panel Member ◽

Multivariable Model ◽

Research Support ◽

Review Panel ◽

Material Support ◽

Advisory Boards ◽

Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

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22. International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Outcome

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.022 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S15-S15

Author(s):

Ray Y Hachem ◽

Anne-Marie Chaftari ◽

Nigo Masayuki ◽

Nelson Hamerschlak ◽

Hiba Dagher ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Cancer Patients ◽

Independent Risk Factor ◽

Panel Member ◽

Low Flow ◽

Treatment Modalities ◽

Research Support ◽

Review Panel ◽

All Cause Mortality

Abstract Background Given the limited collaborative international studies that evaluated COVID-19 in patients with cancer in comparison to patients without cancer, we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods We retrospectively collected de-identified data on cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, at 16 centers in Asia, Australia, Europe, North America, and South America. A logistic regression model was used to identify independent predictors of all-cause mortality within 30 days after COVID-19 diagnosis. Results Of the total 4015 COVID-19 confirmed patients entered, we analyzed 3966 patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were older than non-cancer patients (median age, 61 vs 50 years; p< 0.0001); more likely to be pancytopenic , had pulmonary disorders, hypertension, diabetes mellitus. In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms. By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to 6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who were on high flow oxygen (5.9% vs 17.6%; p=0.03). Patients transfused with convalescent plasma within 1 day of diagnosis had a lower 30-day mortality rate than those transfused later (1% vs 7%, p=0.04). Conclusion Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality, as well as convalescent plasma given early after COVID-19 diagnosis. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support) Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Monica Slavin, MBBS,MD, F2G (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Pfizer (Advisor or Review Panel member) Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)

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1050. Phase 3 Trial to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by 23valent Pneumococcal Polysaccharide Vaccine 6 Months Later in At-risk Adults Aged 18–49 Years (PNEU-DAY): A Subgroup Analysis by Baseline Risk Factors

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1244 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S616-S617

Author(s):

Laura Hammitt ◽

Dean Quinn ◽

Ewa Janczewska ◽

Francisco J Pasquel ◽

Richard Tytus ◽

...

Keyword(s):

Risk Factors ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Baseline Risk ◽

Research Support ◽

Review Panel ◽

Post Vaccination ◽

Study Investigator ◽

Research Grant

Abstract Background Risk factors (RFs) for pneumococcal disease (PD) in immunocompetent individuals include comorbidities, behavioral habits, or living in a community with increased risk of PD transmission. RF stacking of comorbidities is associated with a higher incidence of PD, approaching that of immunocompromised individuals. Pneumococcal vaccination of certain adults is recommended with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) alone/sequentially with pneumococcal conjugate vaccine (PCV). V114, an investigational 15-valent PCV, contains 2 epidemiologically important serotypes (STs), 22F and 33F, in addition to the 13 STs in 13-valent PCV (PCV13). Methods PNEU-DAY was a Phase 3 study evaluating V114 or PCV13 administered on Day 1, and PPSV23 given 6 months later, in adults aged 18–49 years with or without RFs. This subgroup analysis assessed safety, tolerability, and immunogenicity of V114 and PCV13 based on the number of baseline PD RFs, which included chronic liver, lung, and heart disease, diabetes mellitus, tobacco use, and alcohol consumption. Adverse events (AEs; overall and solicited) were collected after each vaccination. Immunogenicity assessment was based on ST-specific opsonophagocytic activity (OPA) at 30 days after each vaccination. Subgroup analyses were conducted by RF group (0, 1, or ≥2 RFs for PD). Results Among the 1515 participants randomized to V114 (n=1135) or PCV13 (n=380), 25.2% had no RFs, 54.7% had 1 RF and 20.1% had ≥2 RFs for PD at baseline. The proportions of participants with solicited AEs following V114/PCV13 and PPSV23 were comparable across the 3 subgroups, with injection-site pain, myalgia, and fatigue being the most common. V114 and PCV13 were immunogenic in all subgroups based on OPA geometric mean titers (GMTs) at 30 days post-vaccination for the 13 shared STs (Figure); in addition, V114 induced a robust immune response to the 2 unique STs (22F, 33F) in all subgroups. PPSV23 following PCV was immunogenic for all 15 STs contained in V114 across all subgroups. Figure. Serotype-specific OPA GMTs at baseline and 30 days post-vaccination with V114 and PCV13 by number of baseline risk factors (per-protocol population) Conclusion V114 administered alone/sequentially with PPSV23 is well tolerated and immunogenic for all 15 vaccine STs, including those not contained in PCV13, in immunocompetent adults aged 18–49 years, regardless of the number of baseline RFs. Disclosures Laura Hammitt, MD, MedImmune (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Merck & Co., Inc. (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Novavax (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)Pfizer (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support) Francisco J. Pasquel, MD, MPH, Boehringer Ingelheim (Consultant)Dexcom (Grant/Research Support)Eli Lilly & Company (Consultant)Insulet (Grant/Research Support)Merck & Co., Inc. (Consultant, Grant/Research Support) K. Rajender Reddy, MD, BMS (Grant/Research Support)Deciphera (Advisor or Review Panel member)Gilead (Grant/Research Support)Grifols (Grant/Research Support)HCC-TARGET (Grant/Research Support)Intercept (Grant/Research Support)Mallinckrodt (Grant/Research Support, Advisor or Review Panel member)NASH-TARGET (Grant/Research Support)Pfizer (Advisor or Review Panel member)Sequana (Grant/Research Support) 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) Rachel Dawson, D.O. MPH, Merck & Co., Inc. (Employee, Shareholder) Jennifer McCauley, BSc, Merck & Co., Inc. (Employee) Kyeongmi Cheon, Ph.D., Merck & Co., Inc. (Employee, Shareholder) Alison Pedley, PhD, Merck & Co., Inc. (Employee) Tina Sterling, BS, Merck & Co., Inc. (Employee, Shareholder) Gretchen Tamms, B.S., Merck Sharp and Dohme (Employee, Shareholder) Luwy Musey, MD, Merck & Co., Inc. (Employee) Ulrike K. Buchwald, MD, MS, Merck & Co., Inc. (Employee)TB Alliance (Employee)

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796. Burden of Healthcare-associated (HA) Respiratory Syncytial Virus (RSV) in Hospitalized Adults

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.992 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S494-S494

Author(s):

Alexandra C Hill-Ricciuti ◽

Edward E Walsh ◽

William G Greendyke ◽

Angela Barrett ◽

Luis Alba ◽

...

Keyword(s):

Risk Factors ◽

Conditional Logistic Regression ◽

Panel Member ◽

Positive Test ◽

Respiratory Support ◽

Respiratory Pathogens ◽

Research Support ◽

Retrospective Case ◽

Review Panel ◽

Syncytial Virus

Abstract Background Little is known about the burden of HA-RSV in hospitalized adults. We assessed risk factors and clinical outcomes in hospitalized adults diagnosed with HA-RSV. Methods A retrospective case-control study was performed from 2017-2020 in two academic hospital systems. HA-RSV cases were >18 years of age, hospitalized >4 days, and developed new or worsening respiratory signs and symptoms that prompted clinicians to test for respiratory pathogens; cases were RSV-positive by PCR assays. Two community-onset (CO) RSV-positive controls (admitted with >2 acute respiratory symptoms), were matched to each HA-RSV case by age, sex, and RSV season. We compared risk factors and outcomes in cases vs. controls. We assessed escalation of respiratory support in HA-RSV cases, defined as new or increased respiratory support from Day -2 to Day +4 of their RSV-positive test. Exact conditional logistic regression compared outcomes of HA-RSV vs. CO-RSV subjects, adjusting for demographic and clinical characteristics. Results 84 cases and 160 controls (both median 64 years) were included; 87% had ≥1 comorbidity. HA-RSV cases were hospitalized for a median of 10 (IQR: 5-17) days prior to their RSV-positive test. CO-RSV controls were more likely to have pulmonary comorbidities than HA-RSV cases (46% vs. 31%, p=0.02). 38% of HA-RSV vs. 15% of CO-RSV subjects were hospitalized ≥15 days after their RSV-positive test (p=0.047). 14% of HA-RSV and 6% of CO-RSV subjects died (p=0.25). Among patients who survived, HA-RSV cases were more likely discharged to a skilled nursing or rehabilitation facility than CO-RSV controls (46% vs. 17%, p=0.04). Of the 44 HA-RSV cases assessed thus far, 25% required escalation of respiratory support; none required initiation of mechanical ventilation. Conclusion HA-RSV was associated with increased morbidity and increased health care resource use during and after hospitalization. RSV vaccines could prevent CO- and HA-RSV infections in adults. Disclosures Edward E. Walsh, MD, GSK (Advisor or Review Panel member)Janssen (Grant/Research Support)Merck (Grant/Research Support)Merck (Grant/Research Support) William G. Greendyke, MD, Merck (Grant/Research Support) Angela Branche, MD, Merck Dohme and Sharpe (Grant/Research Support) Ann Falsey, MD, BioFire Diagnostics (Grant/Research Support)Janssen (Grant/Research Support)Merck (Grant/Research Support)Novavax (Other Financial or Material Support, DSMB member)Pfizer (Grant/Research Support) Matthew R. Phillips, MPH, Merck & Co., Inc. (Employee, Shareholder) Yoonyoung Choi, PhD, MS, RPh, Merck (Employee) Lyn Finelli, DrPH, MS, Merck (Employee) Lisa Saiman, MD, MPH, Merck (Grant/Research Support, Research Grant or Support)Merk Co., Inc (Grant/Research Support, Advisor or Review Panel member)

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889. Early Discontinuations and Adverse Events Among Treatment-Naïve Patients Initiating Integrase Inhibitors in a Real-world Setting

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1084 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S535-S536

Author(s):

Charlotte-Paige M Rolle ◽

Jamie Castano ◽

Vu Nguyen ◽

Kiran Patel ◽

Federico Hinestrosa ◽

...

Keyword(s):

Risk Factors ◽

Adverse Events ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Integrase Inhibitors ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Treatment Naïve

Abstract Background Cohort studies suggest higher rates of discontinuations (DCs) and adverse events (AEs) with integrase inhibitors (INSTIs) than is reported in clinical trials. Here, we assess DC of different INSTIs in combination with one of two tenofovir prodrugs in the first year following initiation defined as “early DC” in a real-world cohort of treatment-naïve patients. Methods This analysis evaluated treatment-naïve patients at a single center initiating raltegravir (RAL), elvitegravir/cobicistat (EVG/c), dolutegravir (DTG) or bictegravir (BIC) in combination with emtricitabine/tenofovir alafenamide (F/TAF) or emtricitabine/tenofovir disoproxil fumarate (F/TDF) between 10/2007-1/2020. Eligible patients had a minimum follow-up of 1 year. The primary endpoint was incidence of early INSTI DC. Secondary endpoints included AEs and risk factors for early INSTI DC and treatment-related AEs. Results 331 patients were included. Median age was 32 years, 89% were male, 43% were non-White, 8% started RAL-based therapy, 46% started EVG/c-based therapy, 22% started DTG-based therapy and 24% started BIC/F/TAF. 36 discontinued INSTI-based therapy early yielding an incidence rate of 0.17 DCs per person-years (PPY) among RAL patients, 0.14 DCs PPY among EVG/c patients, 0.22 DCs PPY among DTG patients, and 0 DCs PPY among BIC patients, p=0.006. Treatment-related AEs occurred in 27% of RAL patients, 42% of EVG/c patients, 50% of DTG patients, and 43% of BIC patients p=0.607; and were responsible for early DC rates of 0.022 in 3 EVG/c patients and 0.075 in 5 DTG patients. No treatment-related early DCs occurred among RAL or BIC patients. No evaluated factor was significantly associated with early INSTI DC, however DTG use was significantly associated with treatment-related AEs (aOR 3.46, 95% confidence interval: [1.20; 10.82]). Table 1. Risk factors for early integrase inhibitor discontinuation and treatment-related adverse events Conclusion In this cohort, early DCs occurred in 11% initiating INSTI-based therapy, however of these only 2% were treatment-related. These data support use of INSTI-based regimens as preferred options for treatment-naïve patients living with HIV due to their favorable safety and tolerability profiles. 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) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Advisor or Review Panel member, Speaker’s Bureau)Theratechonologies (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Scientific Research Study Investigator, Advisor or Review Panel member)

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634. Investigational Microbiome Therapeutic SER-109 Reduces Recurrence of Clostridioides difficile Infection (CDI) Compared to Placebo, Regardless of Risk Factors for Recurrence

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.832 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S420-S420

Author(s):

Stuart H Cohen ◽

Thomas J Louie ◽

Matthew Sims ◽

John Pullman ◽

Elaine E Wang ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Panel Member ◽

Exploratory Analysis ◽

Oral Microbiome ◽

Comorbid Conditions ◽

Research Support ◽

Independent Contractor ◽

Review Panel ◽

Risk Factors For Recurrence

Abstract Background Several demographic and clinical characteristics, including age, sex, medication use and presence of comorbid conditions are considered risk factors for recurrent CDI (rCDI). We examined the efficacy of an investigational purified oral microbiome therapeutic, SER-109, versus placebo in an exploratory analysis of subgroups of patients with risk factors for recurrence who enrolled in ECOSPOR III, a double-blind, placebo controlled trial. Forest Plot of Relative Risks for Recurrence at Week 8 for Selected Baseline Characteristics in the ITT population Methods Patients with ≥ 3 CDI episodes were treated with SER-109 or placebo (four capsules daily for three days) following standard treatment of CDI. The primary efficacy objective was to demonstrate superiority of SER-109 versus placebo in reducing rCDI up to 8 weeks after treatment. In this exploratory analysis, we analyzed the rate of CDI recurrence among SER-109 treated subjects compared to placebo in subgroups defined by rCDI baseline risk factors: proton-pump inhibitor use, number of CDI recurrences, prior FMT history, presence of comorbid conditions and exposure to non-CDI antibiotics after dosing. We also analyzed the rate of CDI recurrence among SER-109 treated subjects by age (≥ 65 and ≤ 65) and gender, which were pre-specified. Results Of 281 patients screened,182 were enrolled. Overall recurrence rates were lower in SER-109 treated patients compared to placebo (12.4% vs 39.8%, respectively); relative risk (RR), 0.32 [95% CI, 0.18-0.58; P< 0.001 for RR< 1.0:P< 0.001 for RR< 0.833]. Co-morbidities including diabetes, renal disease, malignancy, cardiac disease, COPD/asthma, colitis, or immunocompromised status were observed in most patients in the overall study population; 33.5%, 32.4% and 34.1% had 0, 1, or ≥ 2 comorbidities. SER-109 was consistently observed to show greater benefit than placebo in reducing CDI recurrence in all subgroups regardless of the presence or absence of the rCDI risk factor (Fig 1). Conclusion Regardless of risk factor status, SER-109 reduced recurrence of CDI compared to placebo. Most subjects in ECOSPOR III had co-morbidities consistent with the broad inclusion criteria in this Phase 3 trial. Despite a high proportion of patients with co-morbidities in ECOSPOR III, SER-109 significantly reduced the risk of recurrence compared to placebo. Disclosures Stuart H. Cohen, MD, Seres (Research Grant or Support) Thomas J. Louie, MD, Artugen (Advisor or Review Panel member)Crestone (Consultant, Grant/Research Support)Da Volterra (Advisor or Review Panel member)Finch Therapeutics (Grant/Research Support, Advisor or Review Panel member)MGB Biopharma (Grant/Research Support, Advisor or Review Panel member)Rebiotix (Consultant, Grant/Research Support)Seres Therapeutics (Consultant, Grant/Research Support)Summit PLC (Grant/Research Support)Vedanta (Grant/Research Support, Advisor or Review Panel member) Matthew Sims, MD, PhD, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Kelly Brady, MS, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder)

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1523. Seasonal Human Coronavirus Infections Following Allogeneic Hematopoietic Cell Transplantation: Factors Associated With Lower Respiratory Tract Infection

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1704 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S763-S764

Author(s):

Chikara Ogimi ◽

Hu Xie ◽

Alpana Waghmare ◽

Masumi Ueda ◽

Kanwaldeep K Mallhi ◽

...

Keyword(s):

Risk Factors ◽

Tract Infection ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Research Support ◽

Review Panel ◽

Study Investigator

Abstract Background Proven/probable lower respiratory tract infection (LRTI) caused by seasonal human coronaviruses (HCoVs) is associated with mortality after hematopoietic cell transplantation (HCT). However, risk factors for LRTI and the significance of virologic documentation of lower respiratory tract involvement by bronchoalveolar lavage (BAL) on outcome are not well characterized. Methods Patients receiving allogeneic HCT between 4/2008 and 9/2018 with HCoV (OC43/NL63/HKU1/229E) detected in nasopharyngeal or BAL samples by PCR were retrospectively analyzed. Proven/probable LRTI was defined as having virus detected from a BAL sample with or without new pulmonary infiltrates by chest radiography, respectively. Possible LRTI was defined as having virus detected from an upper respiratory tract sample with new pulmonary infiltrates. We used logistic regression models to evaluate risk factors for LRTI in patients with first documented HCoV infection during pretransplant conditioning or post-HCT. Overall mortality following proven/probable and possible LRTI was compared by the log-rank test. Results A total of 297 patients (61 children and 236 adults) developed HCoV infection as follows: 254 had upper respiratory tract infection (URTI) alone, 18 presented with LRTI, and 25 progressed from URTI to LRTI [median 16 days (range, 2–62 days)]. Multivariable analyses showed that male gender, higher immunodeficiency scoring index, albumin < 3 g/dl, glucose > 150 mg/dl and presence of respiratory copathogen at HCoV diagnosis were associated with the occurrence of LRTI (Figure 1). Patients with proven/probable LRTI (N=16) had significantly worse survival than those with possible LRTI (N=37) (p=0.006, Figure 2). Figure 1. Figure 2. Conclusion Our analyses identified risk factors (hypoalbuminemia, male gender, high glucose and presence of respiratory copathogen) uncommonly appreciated for LRTI due to other respiratory viruses in HCT recipients. Whether these factors are also relevant to LRTI due to SARS-CoV-2 after HCT requires further studies. The association of hyperglycemia with LRTI might provide an opportunity to reduce the risk of LRTI. Disclosures Alpana Waghmare, MD, Amazon (Grant/Research Support)Amazon (Employee, Shareholder)Ansun Biopharma (Scientific Research Study Investigator)Kyorin Pharmaceuticals (Advisor or Review Panel member) 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) Michael Boeckh, MD PhD, AlloVir (Consultant)EvrysBio (Advisor or Review Panel member, Other Financial or Material Support, share options)Gilead (Consultant, Grant/Research Support)GSK (Consultant)Helocyte (Advisor or Review Panel member, Shareholder)Lophius (Grant/Research Support)Merck (Consultant, Grant/Research Support)SymBio (Consultant)VirBio (Consultant, Grant/Research Support)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1788 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S798-S799

Author(s):

Nicolo Cabrera ◽

Truc T Tran ◽

Travis J Carlson ◽

Faris Alnezary ◽

William R Miller ◽

...

Keyword(s):

Research Study ◽

Clinical Success ◽

Significant Proportion ◽

Scientific Research ◽

Panel Member ◽

Multidrug Resistant ◽

Outcome Data ◽

Research Support ◽

Gram Negative ◽

Study Investigator

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

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1012. Efficacy, safety and tolerability of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in HIV-1 infected virologically-suppressed older adults in a real-world setting

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1198 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S534-S535

Author(s):

Charlotte-Paige M Rolle ◽

Vu Nguyen ◽

Kiran Patel ◽

Dan Cruz ◽

Federico Hinestrosa ◽

...

Keyword(s):

Older Adults ◽

Drug Interactions ◽

Real World ◽

Research Study ◽

Panel Member ◽

Median Number ◽

Research Support ◽

Review Panel ◽

Study Investigator ◽

Hiv 1

Abstract Background Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Efforts are ongoing to identify antiretrovirals associated with fewer drug-drug interactions (DDIs) and long-term side effects in this group. Clinical trials of B/F/TAF demonstrated favorable efficacy and safety in older adults, however, data from real-word settings are needed to validate these results. Methods This retrospective analysis evaluated records from PLWH aged ≥ 50 years at the Orlando Immunology Center who were switched to B/F/TAF between 2/7/2018 and 5/31/2019. Eligible patients had baseline HIV-1 RNA< 50 copies/mL and were followed for 48 weeks post-switch. The primary endpoint was maintenance of HIV-1 RNA< 50 copies/mL at week 48. The impact of switching to B/F/TAF on DDIs, adverse events (AEs) and safety parameters were analyzed throughout the study. Results 306 patients met inclusion criteria. 62 (20%) were female, 126 (41%) were non-white, median age was 58 years (range [r] 50-81), median duration of HIV infection was 19.5 years (r 2-40), median number of chronic co-morbid conditions was 5 (r 0-20), and median number of baseline concomitant medications was 4 (r 0-23). 159 (52%) patients were switched from regimens containing ritonavir or cobicistat. The most commonly documented reason for switch was simplification (Table 1). At Week 48, 287 (94%) patients maintained an HIV-1 RNA< 50 copies/ml and 19 (6%) had an HIV-1 RNA between 50-200 copies/mL (Figure 1). 1 patient discontinued due to lack of efficacy. A total of 123 potential DDIs were identified in 104 (34%) patients taking a boosting agent or rilpivirine at baseline (Table 2). At Week 48, there was a significant median decline in total cholesterol (15.5 mg/dL, 95% confidence interval [CI]: 9.5; 21.5), LDL cholesterol (9.5 mg/dL, 95% CI: 4; 15.5) and triglycerides (20 mg/dL, 95% CI: 9.5; 32.5), and median weight increased by 2.5 pounds (95% CI: 1.5; 3.5). Treatment-related AEs occurred in 33 (11%) patients (all Grade 1-2) and led to 7 (2%) discontinuations. Table 1-Baseline demographic and clinical characteristics Table 2-Avoidance of Drug-Drug Interactions (DDIs) following switch to B/F/TAF Figure 1-Subgroup analysis of virologic outcomes at Week 48 Conclusion In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, improvement in lipid parameters, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Speaker’s Bureau)Merck (Speaker’s Bureau)Theratechnologies (Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Advisor or Review Panel member)

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652. Comparison of fosfomycin (FOF) activity and prevalence of subpopulations between Escherichia coli (EC) and Klebsiella pneumoniae (KP) during susceptibility testing

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.846 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S384-S384

Author(s):

Jadyn C Anderson ◽

Amanda R Krueger ◽

Elizabeth C Smith ◽

Morgan L Bixby ◽

Hunter V Brigman ◽

...

Keyword(s):

Clinical Efficacy ◽

Inhibitory Concentration ◽

Panel Member ◽

Colony Growth ◽

The United States ◽

Research Support ◽

Review Panel ◽

Agreement Rate ◽

Future Studies ◽

Agar Dilution

Abstract Background In the United States, interpretive criteria for FOF are established only for EC, yet those criteria are often extrapolated to KP. Recent studies have highlighted both inferior clinical outcomes after FOF treatment and difficulties in interpretation of inner colony subpopulations, the presence of which may affect clinical efficacy. We sought to compare FOF activity against EC and KP and to determine the prevalence of inner colony subpopulations following disk diffusion (DD) testing of the two species. Methods A convenience collection of 73 KP and 42 EC isolates from 3 U.S. institutions were included. Minimal inhibitory concentration (MIC) testing was performed in duplicate on separate days using agar dilution (AD) and DD as recommended by the Clinical and Laboratory Standards Institute guidelines, with application of EC susceptibility (≤ 64mg/L) breakpoints. The frequency and counts of inner colonies observed during DD testing was calculated, and colonies were subcultured for use in future studies. Results MIC50/90 values were 1/16 mg/L and 32/256 mg/L for EC and KP respectively. All EC isolates were considered susceptible and therefore categorical agreement was 100%. The majority of KP isolates were considered susceptible (83.6% with AD and 86.3% with DD) and categorical agreement between the methods was 84.9%. Inner colonies were observed during DD testing in 88.1% of EC isolates and 80.8% of KP isolates during at least one replicate, with 47.6% of EC isolates and 39.7% of KP isolates showing inner colony growth during both DD test replicates. More than 10 inner colonies were observed in 50% of EC isolates compared to 12.3% of KP isolates. Conclusion KP isolates demonstrated considerably higher FOF MIC values compared to EC, as evidenced by MIC50/90 values 4-5 dilutions higher than those for EC. The categorical agreement rate was higher among EC than KP, highlighting concerns regarding the practice of extrapolating FOF susceptibility breakpoints for EC to KP. The high frequency of inner colonies observed in DD for both species necessitates further studies to determine best practices for interpreting their relevance, fitness, and resistance in order to identify potential impacts to clinical efficacy of FOF. Disclosures Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)

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