658. Diagnostic Testing Among Patients with Suspected Recurrent Clostridioides difficile Infection (rCDI) in ECOSPOR III a Phase 3 Clinical Trial: Implications for Clinical Practice vs Clinical Trials

Abstract Background Accurate diagnosis of rCDI is challenging because of limitations in test performance and alternative causes of recurrent diarrhea, such as post-infectious irritable bowel syndrome (IBS). Stool enzyme immunoassay (EIA) toxin testing (TOX) is the best predictor of active disease, but may miss cases of CDI when toxins are below the limit of detection. In contrast, glutamate dehydrogenase (GDH) or PCR have high sensitivity but cannot differentiate colonization from infection, leading to possible overdiagnosis due to low specificity. In ECOSPOR III, SER-109, an investigational purified microbiome therapeutic, was superior to placebo in reducing rCDI (12.4% vs 39.8%, respectively; p-value < 0.001). We examined diagnostic testing patterns among screened subjects. Methods Patients with ≥2 prior episodes and ≥3 unformed bowel movements over 48 hours were screened. To ensure enrollment of patients with active CDI, toxin testing was required at entry via a local certified or central lab (Eurofins; Framingham, MA). Subjects with discordant GDH+/TOX- tests at the central lab had reflex confirmatory testing with a cell cytotoxicity neutralization assay (CCNA), considered the “gold standard” for toxin testing. Results The leading reason for screen failure among 281 subjects screened was a negative toxin test (50/99; 50.5%). Of 182 patients enrolled, 59 (32.4%) qualified with EIA TOX+ at the local lab (33 TOX+; 25 GDH+/TOX+) and 122 (67.0%) qualified by the central lab (Table 1). Of these 122 subjects, 87 qualified by GDH+/TOX+ but 35 required additional reflex testing by CCNA due to discordant GDH+/TOX-results; all 35 were positive. Diagnostic Testing for Qualifying C. difficile Episode in ITT Population Conclusion These diagnostic testing patterns suggest a subset of patients with suspected rCDI have toxin concentrations below the EIA threshold for detection or may have an alternative cause of diarrhea, such as post-infectious IBS. Thus, the limitations of EIA toxin testing need to be considered in clinical practice when evaluating patients with compatible symptoms of rCDI and a high prior probability of infection. In contrast, in trials of investigational agents, toxin testing assures enrollment of patients with active disease and accurate estimates of efficacy. Disclosures Matthew Sims, MD, PhD, FACP, FIDSA, 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) Sahil Khanna, MBBS, MS, Seres (Grant/Research Support) Darrell Pardi, MD, seres (Consultant)Vedanta (Consultant) Paul Feuerstadt, MD, FACG, Ferring/Rebiotix Pharmaceuticals (Consultant, Scientific Research Study Investigator, Speaker's Bureau)Finch Pharmaceuticals (Scientific Research Study Investigator)Merck and Co (Speaker's Bureau)SERES Therapeutics (Consultant, Scientific Research Study Investigator)Takeda Pharmaceuticals (Consultant) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder)

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664. LiaX as a Surrogate Marker of Daptomycin Susceptibility in Multidrug-Resistant Enterococcus faecium Recovered from Cancer Patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.857 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S387-S388

Author(s):

Dierdre B Axell-House ◽

Ayesha Khan ◽

Yousif Shamoo ◽

Samuel A Shelburne ◽

Truc T Tran ◽

...

Keyword(s):

Cell Membrane ◽

Enterococcus Faecium ◽

Research Study ◽

Limit Of Detection ◽

Scientific Research ◽

Surrogate Marker ◽

Enzyme Linked Immunosorbent Assay ◽

Whole Cell ◽

Study Investigator ◽

Reference Strains

Abstract Background Vancomycin-resistant Enterococcus faecium (VREfm) are leading causes of bloodstream infections (BSI) in patients (pts) with hematological malignancies (HM). Daptomycin (DAP) is commonly used to treat VRE BSI, but DAP non-susceptibility (DAP-NS) in pts with HM is increasing. Current methods to determine DAP minimum inhibitory concentrations (MICs) have poor reproducibility. DAP triggers the LiaFSR cell membrane stress response pathway, resulting in the extracellular release of the protein LiaX, a novel protein that functions as a regulator of the membrane response. We postulated that detection of extracellular LiaX correlates with DAP-NS in clinical strains of VREfm. Methods We used 6 well-characterized VREfm BSI isolates (2 DAP-S, 4 DAP-NS) as reference strains to optimize a whole-cell indirect enzyme-linked immunosorbent assay (ELISA) method for LiaX detection. We assessed limit of detection and reproducibility of the ELISA LiaX method. We then assessed 54 clinical VREfm BSI isolates from pts with cancer for validation. We determined DAP MICs by broth microdilution (BMD). We collected clinical and microbiological details by chart review Results The 6 reference strains showed high reproducibility with low coefficient of variation. All DAP-NS reference strains had increased detection of LiaX (p< 0.0001) compared to DAP-S reference strains. Of the 54 isolates from pts, most pts (83.3%) had HM. The source of 62.9% of VRE BSIs was determined to be gastrointestinal. Six of the 54 isolates were DAP-NS by BMD MIC. The LiaX test and MIC had categorical agreement on 56% of isolates. Of the isolates with disagreement, 19 isolates were susceptible by MIC (median 2 μg/ml) but non-susceptible by LiaX ELISA, and 5 isolates were non-susceptible by MIC (6, 8, 8, 8, and 16 μg/ml, respectively) but susceptible by LiaX ELISA. Whole-cell indirect LiaX ELISA A405nm of Efm reference strains shows ability to differentiate DAP susceptible MICs from DAP resistant MICs. DAP susceptible (MIC=2 μg/ml) Efm strains are shown in green and DAP resistant (MIC≥8 μg/ml) strains in red. DAP-S reference strains have no LiaFSR mutations. The dotted line indicates an example cutoff for DAP-S/R in this assay. *p<0.05, **p<0.0001 by unpaired t-test. Coefficieint of variance for each reference is <15%. Conclusion Detection of extracellular LiaX has important discrepancies with DAP MIC. Interestingly, LiaX may be a surrogate marker to detect strains with heightened DAP-mediated cell membrane response and potentially identify strains predisposed to DAP therapy failure. Further characterization of the discrepant isolates by genomic analyses and time-kill assays are warranted to fully validate the performance of LiaX ELISA. Disclosures 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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19. The Impact of Investigational Purified Microbiome Therapeutic SER-109 on Health-Related Quality of Life (HRQoL) of Patients with Recurrent Clostridioides difficile Infection (rCDI) in ECOSPOR III, a Placebo-Controlled Clinical Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.019 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S13-S13

Author(s):

Elizabeth Hohmann ◽

Paul Feuerstadt ◽

Caterina Oneto ◽

Charles Berenson ◽

Christine Lee ◽

...

Keyword(s):

Treatment Group ◽

Clinical Outcome ◽

Board Member ◽

Research Study ◽

Scientific Research ◽

Research Support ◽

Independent Contractor ◽

Study Investigator ◽

The Impact ◽

Research Grant

Abstract Background Following standard of care antibiotics, investigational microbiome therapeutic, SER-109, achieved superiority vs placebo (PBO) at 8 weeks in reducing rCDI in patients with ≥3 prior episodes (12.4% vs 39.8%, respectively; p< 0.001). We evaluated the impact of SER-109 vs PBO on HRQoL with general (EQ-5D-5L) and disease-specific (Cdiff32) measures [Garey 2016]. Methods EQ-5D-5L measures outcomes in 5 domains (mobility, self-care, activities, pain/discomfort, and anxiety/depression) while Cdiff32 measures outcomes in 3 domains (physical, mental, and social) including 5 associated subdomains. Patients completed EQ-5D-5L and Cdiff32 measures at baseline (BL), Wk 8, and at recurrence/early termination. Changes from BL were assessed between SER-109 vs PBO and by clinical outcome (recurrence versus nonrecurrence) in the ITT population and within each treatment arm. The between treatment group comparison analysis controlled for age, gender, prior antibiotics, and number of prior CDI episodes. Results Mean EQ-5D-5L and Cdiff32 scores were comparable between SER-109 and PBO at BL. EQ-5D-5L did not detect differences at Wk 8 from BL between SER-109 and PBO or by clinical outcome. In contrast, Cdiff32 detected significant improvements at Wk 8 from BL within both SER-109 subjects and PBO subjects (Fig1) and by recurrence status (Fig2). Subjects achieved significant improvement in all domains at Wk 8 from BL regardless of treatment group. When examining recurrence status within treatment arms, all PBO subjects with non-recurrence showed improvement in all health domains, while PBO subjects with recurrence had declines in several subdomains (Fig3B). Similarly, SER-109 subjects with non-recurrence showed improvement in all domains compared to BL. However, overall and mental domain/subdomains scores also improved in SER-109 subjects with recurrence (Fig3A). Conclusion Significant HRQoL improvements were associated with CDI nonrecurrence, which highlights the negative impact of this debilitating infection. SER-109 was associated with improved overall and mental scores, regardless of clinical outcome. Further investigation is warranted on the impact of SER-109 on mental health even among those with CDI recurrence. Disclosures Elizabeth Hohmann, MD, Seres Therapeutics (Research Grant or Support) Paul Feuerstadt, MD, FACG, Ferring/Rebiotix Pharmaceuticals (Consultant, Scientific Research Study Investigator, Speaker’s Bureau)Finch Pharmaceuticals (Scientific Research Study Investigator)Merck and Co (Speaker’s Bureau)SERES Therapeutics (Consultant, Scientific Research Study Investigator)Takeda Pharmaceuticals (Consultant) Christine Lee, MD, FRCPC, Pfizer (Board Member)Rebiotix-Ferring (Board Member)Rebiotix-Ferring (Grant/Research Support)Seres (Grant/Research Support)Summit (Grant/Research Support) Sissi Pham, PharmD, Seres (Consultant) Pat Ray Reese, PhD, Reese Associates, LLC (Consultant, Independent Contractor) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder) Kevin W. Garey, Pharm.D., M.S., FASHP, Summit Therapeutics (Research Grant or Support)

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422. Performance Evaluation of a Rapid and Easy-to-Use COVID-19 Test

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.616 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S278-S278

Author(s):

Corike Toxopeus ◽

Brian Jones ◽

Jessica Brown ◽

Mark Gurling ◽

Cynthia Andjelic ◽

...

Keyword(s):

Nucleic Acid ◽

Research Study ◽

Limit Of Detection ◽

Scientific Research ◽

Cross Reactivity ◽

External Control ◽

Clinical Samples ◽

Acid Extraction ◽

Clinical Specimens ◽

Study Investigator

Abstract Background The BioFire® COVID-19 Test is a qualitative test for use on the FilmArray® 2.0 and Torch systems for the detection of SARS-CoV-2 RNA in nasopharyngeal swabs (NPS) in transport media. This test received Emergency Use Authorization from the FDA. A closed, disposable pouch contains all the necessary reagents for sample preparation, nucleic acid extraction, reverse transcription, polymerase chain reaction (PCR), and amplified nucleic acid detection to identify RNA from SARS-CoV-2 virus in an NPS specimen. Internal controls monitor all stages of the test process. Once an NPS sample (0.3 mL) is loaded into the system disposable pouch (Figure 1), the fully automated test returns results within an hour. As an additional resource, the BioFire® COVID-19 Test External Control Kit (+) includes positive external control material that may be used for quality control and laboratory verification. Figure 1. BioFire COVID-19 Test Disposable Pouch Methods The following were evaluated: • Limit of Detection (LoD) • Positive and Negative Percent Agreement (PPA and NPA, respectively) for clinical contrived samples and a limited number of clinical specimens • Exclusivity Results • LoD The LoD was evaluated using live SARS-CoV-2 virus (cultured from the USA_WA1/2020 strain obtained from World Reference Center for Emerging Viruses and Arboviruses (WRCEVA)). The LoD was determined to be 3.3E+02 GC/mL (2.2E-02 TCID50/mL). • Clinical Contrived Accurate detection of virus in clinical matrix was demonstrated at various LoD levels using thirty contrived individual unique clinical samples (PPA), and 66 individual unique negative clinical specimens (NPA). • Clinical Samples Positive samples were collected from patients presenting with signs or symptoms of COVID-19, and who were previously identified as positive for SARS-CoV-2 by another EUA test. Negative samples were collected in 2018, and therefore presumed negative for SARS-CoV-2. • Exclusivity The potential for cross-reactivity was evaluated for six viruses from the same genetic family as SARS- CoV-2, and for an additional 30 high priority organisms/viruses. No cross-reactivity was observed. Table 1. SARS-CoV-2 Virus Test Results at 1× and 0.1× LoD for the BioFire COVID-19 Test Table 2. Clinical Contrived and Negative Testing with the BioFire COVID-19 Test Table 3. BioFire COVID-19 Test Performance Summary Conclusion The BioFire COVID-19 Test reliably detects SARS-CoV-2 virus RNA in clinically relevant samples. Disclosures Corike Toxopeus, PhD, BioFire Defense, LLC. (Employee, stock owner) Brian Jones, PhD., BioFire Defense, LLC (Employee, own stock) Jessica Brown, BS, BioFire Defense (Employee, Stock owner) Mark Gurling, PhD, BioFire Defense, LLC (Employee) Cynthia Andjelic, PhD., BioFire Defense (Employee, Other Financial or Material Support, Own stocks) Cynthia L. Phillips, PhD, BioFire Defense (Employee, Scientific Research Study Investigator, Shareholder)BioFire Defense (Employee, Scientific Research Study Investigator, Shareholder)

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1221. Evaluation of the FilmArray® Global Fever Panel

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1406 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S631-S632

Author(s):

Jared R Helm ◽

Brian Jones ◽

Corike Toxopeus ◽

David S Rabiger ◽

Mark Gurling ◽

...

Keyword(s):

Research Study ◽

Limit Of Detection ◽

Scientific Research ◽

Hemorrhagic Fever ◽

Analytical Performance ◽

Prospective Clinical Study ◽

Study Investigator ◽

Percent Agreement ◽

Wide Range ◽

Multiple Pathogens

Abstract Background Acute Febrile Illness (AFI) is caused by a diverse set of pathogens. The FilmArray Global Fever (GF) Panel, developed by BioFire Defense in collaboration with the U.S. Department of Defense and NIAID, uses an automated, multiplex nested PCR system to evaluate whole blood samples for multiple pathogens simultaneously in under an hour. Methods BioFire Defense conducted analytical performance studies to show sensitivity (LoD), inclusivity, and specificity (exclusivity), and a prospective clinical study to evaluate the positive percent agreement (PPA) and negative percent agreement (NPA) of the GF Panel. The results of these studies will be reported in two submissions to the US FDA. Results The analytical performance demonstrated the ability to accurately detect multiple pathogens, including Category A biothreat pathogens. Eleven locations around the world tested 1,865 specimens on the GF Panel. The rate of positive detections was 35% (652/1865), with Plasmodium spp. accounting for the majority of positives (53.4%, 348/652) and dengue virus the second most (40.5%, 264/652). Other detected pathogens include Leptospira spp., West Nile virus, Zika virus, Leishmania spp., Crimean-Congo hemorrhagic fever virus, and chikungunya virus. Twenty-eight (28) specimens had more than one detected pathogen (4.3% of positive specimens). Comparator testing consisted of in-house developed PCR assays followed by bidirectional sequencing. PPA between GF Panel and comparator testing ranged between 92.7-100%, and the NPA ranged between 99.3-100%. In all cases, discrepancies coincided with analytes that were near the limit of detection of the GF Panel and comparator assays. When the GF Panel result was compared to site-specific malaria testing, the PPA ranged between 94.7-100% and the NPA ranged between 43.3-100%. Analysis of the NPA suggests that the GF Panel is more sensitive than microscopy, producing “discrepancies” for this comparison. The wide range in NPA between sites could be due to variation in microscopy technique; the GF Panel eliminates such variation because it is fully automated. Conclusion The results show that the FilmArray GF Panel could aid in rapid and actionable AFI diagnosis caused by multiple, sometimes co-occurring, pathogens. Disclosures Jared R. Helm, PhD, BioFire Defense (Employee) Brian Jones, PhD, BioFire Defense, LLC (Employee, own stock) Corike Toxopeus, PhD, BioFire Defense, LLC. (Employee, stock owner) David S. Rabiger, PhD, BioFire Defense (Employee) Mark Gurling, PhD, BioFire Defense, LLC (Employee) Olivia Jackson, n/a, BioFire Defense (Employee) Marissa Burton, BS Biology, Biomerieux, Inc. (Shareholder) Cynthia Andjelic, PhD, BioFire Defense (Employee, Other Financial or Material Support, Own stocks) Cynthia L. Phillips, PhD, BioFire Defense (Employee, Scientific Research Study Investigator, Shareholder)BioFire Defense (Employee, Scientific Research Study Investigator, Shareholder)

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1051. Rapid onset of seroprotection rates in young adults immunized with a tri-antigenic hepatitis B virus (HBV) vaccine compared to a mono-antigenic HBV vaccine

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1237 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S555-S555

Author(s):

Timo Vesikari ◽

Joanne M Langley ◽

Nathalie Machluf ◽

Johanna Spaans ◽

Bebi Yassin-Rajkumar ◽

...

Keyword(s):

Hepatitis B ◽

Research Study ◽

Scientific Research ◽

Rapid Onset ◽

Independent Contractor ◽

Phase 3 ◽

Younger Adults ◽

Hbv Vaccine ◽

Study Investigator ◽

Research Grant

Abstract Background Hepatitis B (HBV) remains a significant public health risk with an estimated 240-350 million people chronically-infected with HBV worldwide. In the US, rates of new HBV infections are highest among individuals aged 30-39 years, highlighting the elevated risk in adults. Moreover, CDC reported that in 2017 only 34.3% of US adults aged 19-49 years were vaccinated against HBV. Younger adults who are at-risk of HBV infection, through exposure in the workplace or home (e.g. healthcare workers, public service sector workers, those living with HBsAb-positive individuals), through travel to countries with high HBV prevalence, or through exposure as a result of high-risk behavior (e.g. injection drug use, risk through sexual transmission), need a highly effective and safe HBV vaccine with a rapid onset of seroprotection. Seroprotection Rates from Phase 3 Studies Methods Four phase 3 studies assessing kinetics of seroprotection rates (SPR; anti-HBs ≥ 10 mIU/mL) in adults aged 18-45 years, vaccinated at months 0, 1 and 6 with 10 µg of tri-antigenic HBV vaccine (TAV) vs. 20 µg of a mono-antigenic HBV vaccine (MAV) were completed between 2008 & 2020: (1) PROTECT study in US, Europe, and Canada, n = 299; (2) CONSTANT study in US, Europe and Canada, n = 2,838; (3) SG-005-05 study in Vietnam, n = 349; (4) 38-13-040 study in Russia, n = 99. One phase 4, single-arm study was conducted with 10 µg of TAV in adults aged 20-40 years: SciB018 study in Israel, n = 83. Results In all five studies, vaccination with TAV achieved SPRs of 87.2-100.0% at month 6 after 2 doses and 99.2-100.0% at month 7 after 3 doses, compared to 39.0-89.4% and 91.1-98.3% achieved with MAV at months 6 and 7, respectively (Fig 1). Moreover, as demonstrated with the data available from two of the controlled studies, TAV induced SPRs of 76.0%-95.9% at month 3 after 2 doses compared to 37.2%-87.2% with MAV. No major safety signals were observed, and adverse events were well-balanced and consistent with the known vaccine safety profiles. Conclusion Tri-antigenic HBV vaccine (TAV) has demonstrated its ability to rapidly, consistently, and safely elicit high SPRs in younger adults across different regions of the world. Disclosures Joanne M. Langley, MD, GSK group of companies (Research Grant or Support)Immunivaccines Inc (Scientific Research Study Investigator, Research Grant or Support)Janssen (Research Grant or Support)Pfizer (Research Grant or Support)Symvivo (Scientific Research Study Investigator, Research Grant or Support)VBI Vaccines (Research Grant or Support) Nathalie Machluf, PhD, VBI Vaccines Inc. (Employee) Johanna Spaans, BSc, MSc, VBI Vaccines Inc (Employee) Dave Anderson, PhD, VBI Vaccines (Employee, Shareholder) Vlad Popovic, MD, VBI Vaccines, Inc. (Employee, Shareholder) Francisco Diaz-Mitoma, MD, VBI Vaccines, Inc. (Shareholder, Independent Contractor)

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1343 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S605-S605

Author(s):

Pierre Bulpa ◽

Galia Rahav ◽

Ilana Oren ◽

Mickaël Aoun ◽

George R Thompson ◽

...

Keyword(s):

Renal Function ◽

Renal Insufficiency ◽

Antifungal Agents ◽

Research Study ◽

Scientific Research ◽

Panel Member ◽

Antifungal Treatment ◽

Successful Outcome ◽

Review Panel ◽

Study Investigator

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

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1575 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S706-S706

Author(s):

Tanaz Petigara ◽

Ya-Ting Chen ◽

Zhiwen Liu ◽

Michelle Goveia ◽

David Johnson ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

The United States ◽

Vaccination Schedule ◽

Provider Type ◽

Factors Associated ◽

Study Investigator ◽

Region Of Residence ◽

Birth Dose ◽

To Receive

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

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.866 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S391-S391

Author(s):

Maria M Traczewski ◽

Denise Beasley ◽

Amanda Harrington ◽

Sharon DesJarlais ◽

Omai Garner ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Reference Panel ◽

Broth Microdilution ◽

Salmonella Spp ◽

Research Personnel ◽

Gram Negative ◽

Material Support ◽

Study Investigator ◽

Support Research

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

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

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1582 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S708-S709

Author(s):

Ya-Ting Chen ◽

Xinyi Ng ◽

Tanaz Petigara ◽

Jyoti Aggarwal ◽

Jenna Bhaloo ◽

...

Keyword(s):

Research Study ◽

Scientific Research ◽

Physician Attitudes ◽

Combination Vaccine ◽

Hexavalent Vaccine ◽

Family Practitioners ◽

Study Investigator ◽

Vaccine Schedule ◽

Combination Vaccines ◽

Number Of Injections

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

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