scholarly journals 515. Risk Factors for Death, Intubation and Cardiac Arrest among COVID-19 Patients Hospitalized in Eastern North Carolina

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S323-S324
Author(s):  
Adrian Pona ◽  
Yuxuan Mao ◽  
Rahim A Jiwani ◽  
Felix Afriyie ◽  
Jonathan Labbe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiac Arrest ◽  
Clinical Decision Making ◽  
Research Study ◽  
Scientific Research ◽  
Elevated Troponin ◽  
Research Support ◽  
Risk Of Death ◽  
Study Investigator ◽  
Increased Risk

Abstract Background Although majority of coronavirus disease 2019 (COVID-19) cases demonstrate mild to asymptomatic disease, COVID-19 can cause serious complications and death. However, risk factors for development of such complications are not well understood. The purpose of this study was to identify risk factors for intubation, cardiac arrest, and death in COVID-19 patients. Methods A retrospective chart review of COVID-19 subjects was conducted of the first 185 patients for whom we had complete data sets. Subjects were adult inpatients with a confirmed COVID-19 diagnosis who were hospitalized between March and May 2020 at Vidant Medical Center in Greenville, NC. Data including demographics, comorbidities, laboratory results, treatments, and outcomes were collected. Data were analyzed using logistic regression models and receiver operating characteristic curves in SAS 9.4. Results Of the first 185 subjects hospitalized for COVID-19, 26% of patients were intubated, 9% experienced cardiac arrest, and 17% died. Subjects who required intubation were more likely to exhibit elevated triglycerides, sepsis, acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), elevated troponin levels, altered mental status, leukocytosis, lymphopenia and elevated ferritin (P< 0.05) (Table 1). Troponin elevation, ARDS, AKI and thrombocytopenia were risks for cardiac arrest (P< 0.05) (Table 2). Risk of death was increased in those presenting with advanced age, critical or severe disease, lymphopenia or thrombocytopenia, and in those with history of coronary artery disease (CAD) (P< 0.05) (Table 3). Patients presenting with AKI, elevated Troponin, ARDS, pressor requirements, critical disease, and sepsis were at increased risk of intubation, cardiac arrest, and death (P< 0.05) (Tables 1–3). Table 1: Top non-ICU related risk factors for intubation ordered by AUC. Table 2: Top risk factors for cardiac arrest ordered by AUC. Table 3: Top risk factors for death ordered by AUC. Conclusion In this rapidly evolving pandemic, clinician awareness of risk factors for clinically significant outcomes such as intubation and mortality is essential. Assessment of risk factors like those highlighted in this study can aid in clinical decision-making and predicting patient outcomes. As more data becomes available we aim to develop a validated scoring system to assist clinicians in patient care. Disclosures Paul P. Cook, MD, Contrafect (Grant/Research Support, Scientific Research Study Investigator)Gilead (Grant/Research Support, Scientific Research Study Investigator)Leonard-Meron (Grant/Research Support, Scientific Research Study Investigator)Lilly (Grant/Research Support, Scientific Research Study Investigator)

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

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

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

scholarly journals 1076. Gaps in Measles and Mumps Seroprevalence Among Cancer Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S565-S566
Author(s):  
Sara Marquis ◽  
Jennifer Logue ◽  
Tillie Loeffelholz ◽  
Z Z Quinn ◽  
Catherine Liu ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Research Study ◽  
Hematologic Malignancy ◽  
Multivariable Analysis ◽  
Scientific Research ◽  
Current Status ◽  
Cell Transplant ◽  
Research Support ◽  
Study Investigator ◽  
Increased Risk

Abstract Background Immunosuppressed cancer patients are at risk for morbidity and mortality from vaccine preventable diseases. Recent outbreaks and declining vaccination rates put cancer patients at increased risk for measles and mumps exposures. To assess the current status within our center, we measured measles and mumps seroprevalence among cancer patients. Methods Residual clinical plasma samples from patients seen at Seattle Cancer Care Alliance were collected between 8/11/2019 and 8/15/2019 and tested for measles and mumps IgG using ELISA (Genway Biotech); patients receiving intravenous immunoglobulin ≤16 weeks prior to collection date were excluded. Seroprevalence was calculated based on positive results; equivocal results were not considered protective. Demographic and clinical data were abstracted from medical records. Overall and subgroup seroprevalence were estimated with Wilson 95% confidence intervals (CI); Poisson regression with robust standard errors was used to compare subgroups and estimate prevalence ratios (PR). Results Of 1000 unique patients, 987 were eligible, with a median age of 61 years (range 2-97). More than half had a solid tumor (574 [58%]) while 376 (38%) had a hematologic malignancy (HM); 155 (16%) were hematopoietic cell transplant (HCT) recipients. The percentage of seropositive patients was 75% (95% confidence interval [CI]: 72%, 78%) for measles and 62% (95% CI: 59%, 65%) for mumps. Seropositivity was highest among older age groups, particularly those older than 63, who most likely have naturally acquired immunity (Figure 1-2). In multivariable analysis, patients aged 30-59 years were significantly less likely to be seropositive compared to patients ≥80 years of age. Patients with HM and those undergoing HCT were also less likely to be seropositive (Figure 3). Figure 1. Distribution of age at sample collection and measles antibody test results Figure 2. Measles and mumps seroprevalence by age Figure 3. Multivariable model estimates for measles and mumps seroprevalence Conclusion One-quarter of cancer patients tested did not have evidence of seroprotection for measles and mumps. Seronegative and equivocal responses were observed primarily among younger patients and those with hematologic malignancies. Deficits in protective antibody seen in this study are common among cancer patients and underscore the need for population/community-based efforts to increase herd immunity and protect vulnerable populations. Disclosures Helen Y. Chu, MD MPH, Cepheid (Grant/Research Support)Ellume (Grant/Research Support)Glaxo Smith Kline (Consultant)Merck (Consultant)Sanofi-Pasteur (Grant/Research Support) Steven A. Pergam, MD, MPH, Chimerix, Inc (Scientific Research Study Investigator)Global Life Technologies, Inc. (Research Grant or Support)Merck & Co. (Scientific Research Study Investigator)Sanofi-Aventis (Other Financial or Material Support, Participate in clinical trial sponsored by NIAID (U01-AI132004); vaccines for this trial are provided by Sanofi-Aventis)

scholarly journals 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

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)

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

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)

scholarly journals 38. Remdesivir Treatment in Patients Hospitalized with COVID-19: A Comparative Analysis of In-Hospital All-Cause Mortality

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S27-S28
Author(s):  
Essy Mozaffari ◽  
Aastha Chandak ◽  
Zhiji Zhang ◽  
Shuting Liang ◽  
Mark Thrun ◽  
...  
Keyword(s):  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
High Flow ◽  
Low Flow ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Risk Of Death ◽  
Study Investigator

Abstract Background Remdesivir (RDV) reduced time to recovery and mortality in some subgroups of hospitalized patients in the NIAID ACTT-1 RCT compared to placebo. Comparative effectiveness data in clinical practice are limited. Methods Using the Premier Healthcare Database, we compared survival for adult non-mechanically ventilated hospitalized COVID-19 patients between Aug-Nov 2020 and treated with RDV within 2 days of hospitalization vs. those who did not receive RDV. Preferential within-hospital propensity score matching with replacement was used. Patients were matched on baseline O2 and 2-month admission period and were excluded if discharged within 3 days of RDV initiation (to exclude anticipated discharges/transfers within 72 hrs consistent with ACTT-1 study). Time to 14- and 28-day mortality was examined separately for patients on high-flow/non-invasive ventilation (NIV), low-flow, and no supplemental O2 using Cox Proportional Hazards models. Results RDV patients (n=27,559) were matched to unique non-RDV patients (n=15,617) (Fig 1). The two groups were balanced; median age 66 yrs and 73% white (RDV); 68 yrs and 74% white (non-RDV), and 55% male. At baseline, 21% required high-flow O2, 50% low-flow O2, and 29% no O2, overall. Mortality in RDV patients was 9.6% and 13.8% on days 14 and 28, respectively. For non-RDV patients, mortality was 14.0% and 17.3% on days 14 and 28, respectively. Kaplan-Meier curves for time to mortality are shown in Fig 2. After adjusting for baseline and clinical covariates, RDV patients on no O2 and low-flow O2 had a significantly lower risk of death within 14 days (no O2, HR: 0.69, 95% CI: 0.57—0.83; low-flow, HR: 0.67, 95% CI: 0.59—0.77) and 28 days (no O2, HR: 0.80, 95% CI: 0.68—0.94; low-flow, HR: 0.76, 95% CI: 0.68—0.86). Additionally, RDV patients on high-flow O2/NIV had a significantly lower risk of death within 14 days (HR: 0.81, 95% CI: 0.70—0.93); but not at 28 days (Fig 3). Fig 1. Study Population Fig 2. Kaplan-Meier curves among matched patients hospitalized for COVID-19, August-November 2020 Fig 3. Cox proportional hazard model* for time to mortality among matched patients hospitalized for COVID-19, August-November 2020 Conclusion In this large study of patients in clinical care hospitalized with COVID-19, we observed a significant reduction of mortality in RDV vs. non-RDV treated patients in those on no O2 or low-flow O2. Mortality reduction was also seen in patients on high-flow O2 at day 14, but not day 28. These data support the use of RDV early in the course of COVID-19 in hospitalized patients. Disclosures Essy Mozaffari, PharmD, MPH, MBA, Gilead Sciences (Employee, Shareholder) Aastha Chandak, PhD, Gilead Sciences (Other Financial or Material Support, Employee of Certara (contracted by Gilead to conduct this study)) Zhiji Zhang, MS, Gilead Sciences (Other Financial or Material Support, Employee of Certara (contracted by Gilead to conduct this study)) Shuting Liang, MPH, Gilead Sciences (Employee) Mark Thrun, MD, Gilead Sciences (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) Daniel R. Kuritzkes, MD, Abpro (Consultant)Atea (Consultant, Scientific Research Study Investigator)Decoy (Consultant)Gilead Sciences (Consultant, Grant/Research Support)GSK (Consultant)Janssen (Consultant)Merck (Consultant, Grant/Research Support)Novartis (Scientific Research Study Investigator)Rigel (Consultant)ViiV (Consultant, Grant/Research Support) Paul Sax, MD, Gilead Sciences (Consultant, Grant/Research Support)Janssen (Consultant)Merck (Consultant, Research Grant or Support)ViiV (Consultant, Research Grant or Support) David Wohl, MD, Gilead Sciences (Consultant, Grant/Research Support, Advisor or Review Panel member)Janssen (Consultant, Advisor or Review Panel member)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member)ViiV (Consultant, Grant/Research Support, Advisor or Review Panel member) Roman Casciano, M.Eng, Gilead Sciences (Other Financial or Material Support, Employee of Certara (contracted by Gilead to conduct this study)) Paul Hodgkins, PhD, MSc, Gilead Sciences (Employee, Shareholder) Richard Haubrich, MD, Gilead Sciences (Employee, Shareholder)

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

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)

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

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S798-S799
Author(s):  
Nicolo Cabrera ◽  
Truc T Tran ◽  
Travis J Carlson ◽  
Faris Alnezary ◽  
William R Miller ◽  
...  
Keyword(s):  
Research Study ◽  
Clinical Success ◽  
Significant Proportion ◽  
Scientific Research ◽  
Panel Member ◽  
Multidrug Resistant ◽  
Outcome Data ◽  
Research Support ◽  
Gram Negative ◽  
Study Investigator

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

scholarly journals 798. Metronidazole Exposure Prior to Clostridiodes difficile Infection (CDI) is a Risk Factor for Severe C. difficile Disease in Cancer Patients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S442-S443
Author(s):  
Denise Marie A Francisco ◽  
Liangliang Zhang ◽  
Ying Jiang ◽  
Adilene Olvera ◽  
Eduardo Yepez Guevara ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Cancer Patients ◽  
Research Study ◽  
Research Support ◽  
Factors Associated ◽  
Patients With Cancer ◽  
Study Investigator ◽  
Severity Levels ◽  
Permutation Analysis

Abstract Background Antibiotic use is a risk factor for CDI. Few studies have correlated use of prior antibiotics with CDI severity in cancer patients. This study identified clinical and microbiology risk factors associated with severe CDI in patients with cancer. We hypothesized that previous antibiotic exposure and microbiome composition at time of CDI presentation, are risk factors for severe disease in cancer patients. Methods This non-interventional, prospective, single-center cohort study examined patients with cancer who had their first episode or first recurrence of CDI between Oct 27, 2016 and Jul 1, 2019. C. difficile was identified using nucleic acid amplification testing. Multivariate analysis was used to determine significant clinical risk factors for severe CDI as defined in the 2018 IDSA/SHEA guidelines. Alpha, and beta diversities were calculated to measure the average species diversity and the overall microbial composition. Differential abundance analysis and progressive permutation analysis were used to single out the significant microbial features that differed across CDI severity levels. Results Patient (n=200) demographics show mean age of 60 yrs., 53% female, majority White (76%) and non-Hispanic (85%). Prior 90 day metronidazole use (Odds Ratio OR 4.68 [1.47-14.91] p0.009) was a significant risk factor for severe CDI. Other factors included Horn’s Index > 2 (OR 7.75 [1.05-57.35] p0.045), Leukocytosis (OR 1.29 [1.16-1.43] p< 0.001), Neutropenia (OR 6.01 [1.34-26.89] p0.019) and Serum Creatinine >0.95 mg/dL (OR 25.30 [8.08-79.17] p< 0.001). Overall, there were no significant differences in alpha and beta diversity between severity levels. However, when identifying individual microbial features, the high presence of Bacteroides uniformis, Ruminococceae, Citrobacter koseri and Salmonella were associated with protection from severe CDI (p< 0.05). Table 1 - Results of multivariate logistic regression analysis of factors associated with severe CDI Figure 1. Microbiome features identified by progressive permutation analysis as seen in a volcano plot. Conclusion A number of risk factors for severe CDI were identified among this population, including prior 90 day metronidazole use. Also, increased relative abundance of Bacteroides uniformis, Ruminococceae, Citrobacter koseri and Salmonella were linked to protection from severe CDI. Reducing metronidazole use in patients with cancer may help prevent subsequent severe CDI. Disclosures Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Kevin W. Garey, PharmD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator) Ryan J. Dillon, MSc, Merck & Co., Inc., (Employee) Engels N. Obi, PhD, Merck & Co. (Employee)

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

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

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

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

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

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

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