scholarly journals Via media: Role and responsibilities of the independent safety officer

2019 ◽  
Vol 3 (4) ◽  
pp. 147-151
Author(s):  
M. E. B. Holbein ◽  
Barbara N. Hammack ◽  
Ann J. Melvin ◽  
Tamsin A. Knox
Keyword(s):  
Research Study ◽  
Scientific Information ◽  
Safety Data ◽  
Minimal Risk ◽  
Middle Way ◽  
Study Progress ◽  
Study Investigator ◽  
Risk Research ◽  
Safety Officer ◽  
Regulatory Challenges

AbstractEvery research study that includes volunteer participants requires safety assurances in proportion to the risks of the study. Investigator-initiated clinical research can present unique regulatory challenges particularly for studies with a risk profile that warrants more oversight than minimal risk but less than for large, commercial, or high-risk research. The use of an independent safety officer (ISO) offers a middle way of right-sizing oversight to match the risk. ISOs are clinicians or researchers with relevant expertise who are independent of the investigator and the research study. Their relationship to the study is defined by a formal charter which is aligned with the protocol and Data and Safety Monitoring Plan to address the oversight process, responsibilities of the ISO, and clearly describe the variables to be monitored. The ISO responsibilities include reviewing safety data, adverse events, recruitment, demographics, study progress, data quality, protocol changes, and any new scientific information that pertains to the trial. Finally, the ISO reports in their review on any significant findings may propose modifications to the study or a need to stop the trial.

Obtaining surrogate consent for a minimal-risk research study in the intensive care unit setting

2012 ◽  
Vol 10 (1) ◽  
pp. 93-96 ◽  
Author(s):  
Mary E Larkin ◽  
Catherine C Beauharnais ◽  
Kendra Magyar ◽  
Laurel Macey ◽  
Kerry B Grennan ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Research Study ◽  
Intensive Care Unit Setting ◽  
Minimal Risk ◽  
Risk Research ◽  
Surrogate Consent

scholarly journals 561. Safety of Remdesivir vs Standard Care in Patients with Moderate Covid-19

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S345-S346
Author(s):  
Gerard J Criner ◽  
Gerard J Criner ◽  
Mi Young Ahn ◽  
Gregory Huhn ◽  
Aruna Subramanian ◽  
...  
Keyword(s):  
Research Study ◽  
Safety Data ◽  
Scientific Research ◽  
Standard Of Care ◽  
Liver Function Tests ◽  
Similar Rate ◽  
Research Support ◽  
Open Label ◽  
Study Investigator ◽  
Open Label Phase

Abstract Background Remdesivir (RDV) has been shown to shorten recovery time and was well tolerated in patients with severe COVID-19. Here we report safety of RDV in patients with moderate COVID-19. Methods We conducted an open-label, phase 3 trial (NCT04252664) in hospitalized patients with confirmed SARS-CoV-2 infection, evidence of pulmonary infiltrates, and oxygen saturation >94% on room air. Patients were randomly assigned to receive RDV (5 or 10 days) or standard of care (SOC). RDV was dosed intravenously at 200 mg on day 1, 100 mg daily thereafter. Adverse events (AEs) and laboratory abnormalities were evaluated through the day 11 data cut; safety data through day 28 will be presented at the meeting. Results 584 patients were randomized and treated (5d RDV: n=191; 10d RDV, n=193; SOC: n=200). Baseline characteristics were balanced among groups; median (range) age was 57y (12-95y), 39% were female and 19% Black, 39% had arterial hypertension, 15% hyperlipidemia, 11% asthma. Briefly, across both the 5d and 10d arms, RDV was well tolerated with a similar rate of Grade 3 or 4 AEs and fewer SAEs compared to SOC (Table). AEs more common with RDV vs SOC included nausea, headache, and hypokalemia. Overall, across the 3 arms, incidence of AEs leading to discontinuation and death were low and no clinically relevant changes in laboratory parameters were observed. In addition, median changes in renal and liver function tests from baseline were not statistically significant between the RDV 5d and RDV 10d groups compared to the SOC only group at d14 (Table 1). Table 1. Conclusion RDV given for 5d or 10d was well tolerated in patients with moderate COVID-19. No clinically significant safety signals were observed with RDV vs SOC. Disclosures Gerard J. Criner, MD, Gilead Sciences Inc. (Scientific Research Study Investigator)Regeneron (Scientific Research Study Investigator) Gerard J. Criner, MD, NO DISCLOSURE DATA Mi Young Ahn, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Gregory Huhn, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator)Janssen (Grant/Research Support)Proteus (Grant/Research Support)US National Institutes of Health (Grant/Research Support)Viiv Healthcare (Grant/Research Support) Aruna Subramanian, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Carlos Lumbreras, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Stefan Schmiedel, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Robert H. Hyland, MD, Gilead Sciences Inc. (Employee, Shareholder) Vithika Suri, PhD, Gilead Sciences Inc. (Employee, Shareholder) Huyen Cao, MD, Gilead Sciences Inc. (Employee, Shareholder) Hongyuan Wang, PhD, Gilead Sciences Inc. (Employee, Shareholder) Devi SenGupta, MD, Gilead Sciences Inc. (Employee, Shareholder) Anand Chokkalingam, PhD, Gilead Sciences (Employee) Anu Osinusi, MD, Gilead Sciences (Employee) Diana M. Brainard, MD, Gilead Sciences (Employee) Yao-Shen Chen, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Yao-Shen Chen, MD, NO DISCLOSURE DATA Huldrych Günthard, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) D Jose Sanz-Moreno, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Judith A. Aberg, MD, Theratechnology (Consultant) Emanuele Nicastri, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Owen Tak-Yin Tsang, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Owen Tak-Yin Tsang, MD, NO DISCLOSURE DATA

scholarly journals 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

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)

scholarly journals 139. association of Physician Orders for Life-sustaining Treatment (POLST) with Antimicrobial Use at End of Life in Cancer Patients: An Antimicrobial Stewardship Opportunity

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S199-S200
Author(s):  
Olivia Kates ◽  
Elizabeth M Krantz ◽  
Juhye Lee ◽  
John Klaassen ◽  
Jessica Morris ◽  
...  
Keyword(s):  
End Of Life ◽  
Cancer Patients ◽  
Symptom Management ◽  
Research Study ◽  
Antibiotic Use ◽  
Antimicrobial Use ◽  
Study Investigator ◽  
Days Of Therapy ◽  
Life Sustaining Treatment ◽  
Rate Ratios

Abstract Background IDSA/SHEA guidelines recommend that antimicrobial stewardship programs support providers in antibiotic decisions for end of life care. Washington State Physician Orders for Life-Sustaining Treatment (POLST) forms allow patients to indicate antimicrobial use preferences. We sought to characterize antimicrobial use in the last 30 days of life for cancer patients by presence of a POLST and antimicrobial use preferences. Methods We performed a single-center, retrospective cohort study of cancer patient deaths from January 1, 2016 - June 30, 3018. Patient demographics, clinical characteristics, POLST, and antimicrobial use within 30 days before death were extracted from electronic records. To test for an association between POLST completed at least 30 days before death and inpatient antimicrobial days of therapy (DOT) in the 30 days before death, we used negative binomial models adjusted for age, sex, race, and service line (hematologic versus solid malignancy); model estimates are presented as incidence rate ratios (IRR) with 95% confidence intervals (CI) Results Of 1796 patients, 406 (23%) had a POLST. 177/406 (44%) were completed less than 30 days before death, and 58/177 (32.8%) specified limited antibiotic use; 40/177 (23%) did not specify any antimicrobial use preference (Fig 1). Of 1295 patients with at least 1 inpatient day in the 30 days before death, 1070 (83%) received at least 1 inpatient antimicrobial with median DOT of 1077 per 1000 inpatient days (Tab 1). There was no difference in DOT among patients with and without a POLST > /= 30 days before death (IRR 0.92, CI 0.77, 1.10). Patients with a POLST specifying limited antibiotic use had significantly lower inpatient IV antimicrobial DOT compared to those without a POLST (IRR 0.64, CI 0.42–0.97) (Fig 2). Figure 1. Classification of Patients by Presence of POLST, Timing, and Antimicrobial Preference Content of POLST. Numbers shown represent the number of patients (percentage). Full antibiotic use refers to the selection “Use antibiotics for prolongation of life.” Limited antibiotic use refers to the selection “Do not use antibiotics except when needed for symptom management.” Table 1: Antimicrobial use for all patients and by advance directive group Figure 2. Forest plot of model estimates, represented as incidence rate ratios (IRR) with 95% confidence intervals (CI), for associations between POLST antimicrobial specifications completed at least 30 days before death and inpatient antibiotic days of therapy (DOT) in the 30 days before death. Estimates represent comparisons between each POLST category and no POLST completed at least 30 days before death. Dots represent the IRR and brackets extend to the lower and upper limit of the 95% CI. Blue estimates are for the inpatient antibiotic DOT outcome and red estimates are for the inpatient IV antibiotic DOT outcome. Conclusion POLST completion is rare > /= 30 days before death, with few POLSTs specifying antimicrobial use. Compared to those with no POLST in this time frame, patients who indicated that antibiotics should be used only for symptom management received significantly fewer inpatient IV antimicrobials. Early discussion of advance directives including POLST with specification of antimicrobial use preferences may promote more thoughtful use of antimicrobials near the end of life in a compassionate, patient-centered way. Disclosures 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 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 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

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)

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

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)

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

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)

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

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)

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