bluuebunny/crossref_metadata_2025_split huggingface dataset:
634. Chlorhexidine Oral Rinses to Alter the Oral and Sputum Microbiota in COPD (CLIMB): a Randomized, Double-blinded, Placebo-controlled, Parallel-group Pilot Study
Authors: Pragman Alexa , Fieberg Ann , Reilly Cavan , Wendt Chris 
Published: January 2021

Abstract

Background
Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory lung disease with few available disease-modifying therapies. Acute exacerbations of COPD (AECOPD) increase morbidity and mortality, and their occurrence coincides with sputum and oral microbiota dysbiosis. The oral microbiota also serves as the source of the lower airway microbiota. Chlorhexidine oral rinses are known to alter the oral microbiota. We hypothesized that subjects randomized to 8 weeks of chlorhexidine oral rinses (vs. placebo) will demonstrate decreased microbiota biomass compared to baseline and those on placebo.

Methods
We performed a randomized, double-blind, placebo-controlled, 8-week study of the effects of twice-daily chlorhexidine oral rinses on 44 subjects with COPD. Baseline and post-treatment data were obtained evaluating oral and sputum microbiota biomass and composition, systemic inflammation (CRP, fibrinogen, and WBC count), and respiratory symptoms (Breathlessness, Cough, and Sputum Scale [BCSS], St. George’s Respiratory Questionnaire [SGRQ], and AECOPD assessment). All analyses were prespecified.

Results
Forty of 44 participants completed the study. The primary analysis of the mean differences in oral and sputum microbiota biomass between treatment groups was not significant. Chlorhexidine use was associated with a decrease in oral and sputum microbiota alpha diversity compared with placebo (Shannon diversity index change [standard error]: -0.349 [0.091] and -0.622 [0.169] respectively; padj=0.001 for both). There was no significant change in CRP, fibrinogen, WBC count, or BCSS score between treatment groups over the study period. Chlorhexidine use was associated with a significant improvement in SGRQ score when compared to the placebo (mean change ± standard deviation: chlorhexidine -4.7 ± 8.0 vs. placebo 1.7 ± 8.9, p=0.011; minimal clinically important difference in SGRQ score -4). Few adverse events were reported.

Conclusion
Among those with COPD, use of twice-daily chlorhexidine oral rinses resulted in decreased oral and sputum microbiota alpha diversity and clinically significant improvement in COPD symptoms. Chlorhexidine use did not result in decreased oral or sputum microbiota biomass or decreased systemic inflammation.

Disclosures
All Authors: No reported disclosures
636. Immunogenicity, Safety and Tolerability of a Booster Dose of Clostridium difficile Vaccine and 4 Year Antibody Persistence
Authors: Remich Shon A , Kitchin Nicholas , Pride Michael W , Anderson Annaliesa S , Li Ping , Webber Chris 
Published: January 2021

Abstract

Background
Clostroidides difficile (C difficile) is a common cause of antibiotic-associated diarrhea. To date, there is no vaccine to prevent C. difficile infection (CDI). This extension of a phase 2 study explores the immunogenicity, safety, and tolerability of a 4th dose, and antibody persistence of a three-dose regimen of a toxoid-based C difficile vaccine in 300 healthy adults 65 to 85 years of age in the United States.

Methods
The first stage of this study was conducted from 16 July 2015 to 7 March 2017, in which subjects were enrolled and randomized to receive one of two antigen dose levels (100µg or 200µg total toxoid A and B) or placebo, administered in one of two three-dose regimens: Days 1, 8 & 30 or Months 0, 1 & 6. Immunogenicity testing was conducted on samples obtained at each of nine study visits through 12 months post dose 3. In this extension stage, subjects who had received vaccine in the first stage were re-randomized at 12 months post dose 3 to receive either a booster dose or placebo in a 1:1 ratio. Subjects were followed for immunogenicity three (3) years post booster (four years post dose #3)

Results
Peak antibody response to vaccination was observed between day 8 and 30 following booster administration. Both regimens demonstrated robust anamnestic responses with peak levels above the three-dose peak (stage 1). Toxin A geometric mean concentrations (GMCs) remained above pre-booster GMCs, 3 years post booster for both dose levels and regimens. Antibody persistence for both groups demonstrated stable antibody levels four years after the primary vaccination series among subjects who did not receive a booster dose. No Grade 4 reactogenicity was reported during the study. Pain was the most common local reaction. Adverse event rates per subject were similar between both regimens and placebo. There were no Serious Adverse Events (SAEs) considered related to the investigational product at any dose or regimen. The safety profile was consistent with what was seen in the first stage of the study.

Conclusion
A booster dose of Clostroidides difficile vaccine candidate is highly immunogenic, well tolerated and demonstrates an acceptable safety profile in both dose groups for the Day and the Month regimens. Antibody persistence remains stable from 12 months to 4-year post dose 3.

Disclosures
Nicholas Kitchin, MD, Pfizer, Inc (Employee) Michael W. Pride, PhD, Pfizer (Employee, Shareholder) Annaliesa S. Anderson, PhD, Pfizer (Employee, Shareholder) Chris Webber, MD, Pfizer Inc (Employee, Shareholder)
637. Outcomes by Body Mass Index (BMI) in the STRIVE Phase 2 Trial of Once-Weekly Rezafungin for Treatment of Candidemia and Invasive Candidiasis Compared with Caspofungin
Authors: Vazquez Jose A , Flanagan Shawn , Pappas Peter , Thompson George R , Sandison Taylor , Honore Patrick M 
Published: January 2021

Abstract

Background
There is increasing evidence of antifungal underdosing in the treatment of invasive disease, particularly in special populations such as the obese. Body size is often an important variable affecting drug exposure, and pharmacokinetic (PK) models of antifungal dosing have suggested size-based dose adjustments to achieve target drug exposure.
Rezafungin (RZF) is a novel echinocandin in Phase 3 development for treatment of candidemia and invasive candidiasis (IC) and for prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis in blood and marrow transplant recipients. Distinctive PK properties of RZF (e.g., long half-life, extensive tissue distribution, and front-loaded drug exposure) lend themselves to RZF once-weekly (QWk) dosing and antifungal efficacy. In this sub-analysis of the Phase 2 STRIVE trial of RZF in the treatment of candidemia and/or IC, outcomes based on patient BMI were evaluated.

Methods
The STRIVE trial (NCT02734862) compared the safety and efficacy of RZF QWk compared with once-daily caspofungin (Fig. 1). For this subanalysis, data were stratified by BMI categories of &lt; 30 kg/m2 and ≥ 30 kg/m2. Efficacy (overall response [resolution of clinical signs of infection + mycological eradication], mycological response, and investigator assessment of clinical response) and safety (treatment-emergent adverse events [TEAEs]) endpoints by treatment group were evaluated, as well as PK data (area under the curve [AUC]) from RZF-treated patients.
Figure 1.

Results
Mean BMI values were similar across treatment arms (26.9 kg/m2 in RZF Group 1 and 26.8 kg/m2 in RZF Group 2 and CAS arms). Efficacy outcomes at Day 14 were similar between BMI categories (Table 1). Rates of TEAEs were generally similar between BMI categories as well (Table 2), with no concerning safety trends. Following one dose of RZF 400 mg (Week 1), the ranges of AUCs by BMI category overlapped and there was a minor mean difference of ~20% (lower for those with BMI ≥ 30 kg/m2) (Fig. 2).
Table 1

Table 2

Figure 2.

Conclusion
The safety, efficacy, and PK of RZF in the Phase 2 STRIVE trial was consistent across BMI categories. These results suggest that dose adjustments in obese patients are not necessary. These findings contribute to the evaluation of RZF in a range of patient populations and its ongoing development.

Disclosures
Shawn Flanagan, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder) Patrick M. Honore, MD, PhD, FCCM, Cidara Therapeutics, Inc. (Scientific Research Study Investigator)
639. Short Course Therapy for Urinary Tract Infections (SCOUT) in Children
Authors: Zaoutis Theoklis , Bhatnagar Sonika , Black Stephen I , Coffin Susan E , Coffin Susan E , Downes Kevin J , Fisher Brian T , Fisher Brian T , Gerber Jeffrey , Green Michael D , Lautenbach Ebbing , Liston Kellie , Martin Judith , Muniz Gysella , Myers Sage R , O’Connor Shawn , Rowley Elizabeth , Shaikh Nader , Shope Timothy , Hoberman Alejandro 
Published: January 2021

Abstract

Background
The AAP recommends 7 to 14-days of antimicrobials for the treatment of urinary tract infections (UTIs), one of the most common bacterial infections of childhood. However, most physicians routinely prescribe at least 10 days of therapy. Prior observational studies suggest that courses shorter than 10 days might be effective.

Methods
The primary objective was to determine if halting antimicrobial therapy in children who improved clinically after 5 days of therapy (short course therapy) results in a similar failure rate as children who continue antimicrobials for an additional 5 days (standard course therapy).
This was a multi-center, randomized, double-blind, placebo-controlled non-inferiority clinical trial of children ages 2 to 10 years with UTI. Subjects treated with 1 of 5 antibiotics (trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, cefixime, cefdinir or cephalexin) were eligible. Children were stratified by presence or absence of fever and were enrolled if they had clinical improvement before Day 5 of treatment. The a priori equivalence interval was set at 0.05 for a one-sided analysis. The primary outcome was development of a symptomatic UTI defined as the presence of symptoms, pyuria, and a positive urine culture. The Intent-to-Treat population included children who took at least one dose of study medication.

Results
A total of 693 children were randomized, 345 to short course and 348 to standard course. Median age was 4 years old (IQR; 2-6), 652 (96.3%) were female and 255 were febrile (37%). Treatment success rate was 322/336 (96%) for short course and 326/328 (99%) for standard course. The 95% upper CI limit for the difference was 0.054. Treatment failure was not related to age group, fever at presentation, antibiotic type, or study site. There were no significant differences between groups the in the rates of adverse events, recurrent infection, clinical symptoms that may have been related to UTI, or emergent antibiotic resistance.

Conclusion
In children aged 2 months to 10 years with UTI, halting antimicrobial therapy in children who had exhibited clinical improvement after 5 days and continuing for an additional 5 days both resulted in high success rates. However, short course was inferior to treatment for 10 days.

Disclosures
Kevin J. Downes, MD, Merck, Inc. (Grant/Research Support) Brian T. Fisher, DO, MPH, MSCE, Astellas (Advisor or Review Panel member)Merck (Grant/Research Support)Pfizer (Grant/Research Support)
644. Borrelia miyamotoi and Borrelia burgdorferi Seroprevalence in New England
Authors: Johnston Demerise , Kelly Jill , Ledizet Michel , Lavoie Nathalie , Krause Peter J 
Published: January 2021

Abstract

Background
Diseases vectored by the tick species Ixodes scapularis have increased in incidence over the past 50 years and have been expanding into previously non-endemic areas. The emergence of Borrelia miyamotoi, a recently described spirochetal pathogen, has been less well documented than that of Borrelia burgdorferi, the causative agent of Lyme disease. The objective of this study was to compare the geographic range of human exposure to B. miyamotoi and B. burgdorferi in New England, the pattern of their spatial expansion, and factors that influence their frequency.

Methods
Serum samples were collected from 11 study sites across New England. Age, gender, race, and residential zip code or county were recorded for each study participant and aggregate data analyzed by study sites, study site zones, and residential county for spatial analysis. Serum samples were tested for B. miyamotoi antibody using a multiplex Luminex assay and for B. burgdorferi antibody using a recently FDA approved two-tiered ELISA (Zeus ELISA Test Systems). Fischer exact tests and map visualizations in ArcGIS Pro 2.4.2 (Copyright ©2019 Esri Inc.) were used to determine spatial distribution of human B. miyamotoi and B. burgdorferi infection in New England. A logistic regression model was used to determine any association in seropositivity with tick-borne infection risk factors.

Results
B. burgdorferi seroprevalence was greater than that of B. miyamotoi at all but one study site. The average B. burgdorferi seroprevalence at all study sites was not quite double that of B. miyamotoi (mean 2.3% [0.6-6.2%] and mean 4.1% [2.2-7.5%], respectively). No longitudinal or latitudinal gradient was observed for B. miyamotoi or B. burgdorferi seroprevalence by study site zone or county analysis. Men were twice as likely as women to be seropositive for B. miyamotoi and B. burgdorferi.

Conclusion
Human exposure to B. miyamotoi and B. burgdorferi is highly dispersed throughout New England. B. miyamotoi seroprevalence is about half that of B. burgdorferi in New England. Additional studies are needed to explain the disparity between B. burgdorferi and B. miyamotoi infection and disease.

Disclosures
All Authors: No reported disclosures
647. Adoption of the updated fluoroquinolones breakpoints for Gram negative bacteria in clinical microbiology laboratories
Authors: Sfeir Maroun M 
Published: January 2021

Abstract

Background
Despite the multiple safety warnings related to fluoroquinolones (FQs) treatment, their use remains unavoidable in several occasions due to their broad spectrum of coverage including activity against multi-drug resistant glucose non-fermenting Gram-negative bacteria such as Pseudomonas spp., and high oral bioavailability. The Clinical and Laboratory Standards Institute (CLSI) has lowered the FQs minimal inhibitory concentrations (MICs) breakpoints for Salmonella spp. in 2012 and 2013, and for the Enterobacterales and P. aeruginosa in 2019. We aim to explore the number of hospitals that adopted the revised breakpoints.

Methods
We conducted a cross-sectional phone-based survey querying the 43 microbiology laboratories that serve 100% of the acute care and long-term hospitals in Connecticut to determine use of revised FQs MIC breakpoints for Gram-negative bacteria.

Results
Six laboratories refer antimicrobial susceptibility testing to another local hospital microbiology laboratory or to a national reference laboratory. Thus, we obtained information about the study question from a total of 37 microbiology laboratories. Eight laboratories (21.6%) were affiliated to university hospitals and 29 (78.4%) were community-based. Microscan Beckman coulter MicroScan was the most common antimicrobial susceptibility test method used in 15 (40.6%) microbiology laboratories followed by BioMérieux Vitek 2 in 13 (35.1%) laboratories. Four laboratories (10.8%) only adopted the revised CLSI FQs breakpoints for Enterobacterales, P. aeruginosa, and Salmonella spp, 5 (13.5%) implemented the revised breakpoints for Enterobacterales and P. aeruginosa but not for Salmonella spp., and 8 (21.6%) laboratories adopted the revised CLSI breakpoints for Salmonella spp. but not for Enterobacterales and P. aeruginosa.

Conclusion
The use of outdated CLSI breakpoints for FQs against Gram-negative bacteria remains common in the microbiology laboratories. There is an urgent need to mitigate the impact of using the outdated FQs breakpoints and reporting false susceptibility to FQs.

Disclosures
All Authors: No reported disclosures
648. BioFire® FilmArray® Pneumonia plus Panel Performance Evaluation: A Multicenter, International Collaborative Study
Authors: Ginocchio Christine C , Mauerhofer Barbara , Rindlisbacher Cory , Garcia Carolina 
Published: January 2021

Abstract

Background
Classical methods to identify causes of community acquired, healthcare and ventilator associated pneumonia can be insensitive and slow, leading to unnecessary or inappropriate antimicrobial therapy. The BioFire® FilmArray® Pneumonia plus Panel (PNplus) detects 15 bacteria (in semi-quantitative log bin values from 10^4 to &gt; 10^7), 7 antibiotic resistance markers (mecA/C/MREJ, CTX-M, KPC, VIM, IMP, NDM, OXA-48 like), 3 atypical bacteria (AB), and 8 viral classes directly from bronchoalveolar lavage (BAL)-like and sputum-like specimens (including endotracheal aspirates) in about 1 hr. This study compared PNplus results to standard of care testing (SOC).

Methods
2476 samples (1234 BAL-like; 1242 sputum-like) were tested at 52 laboratories from 13 European countries and Israel by PNplus and SOC. SOC varied by site and physician prescription. Pathogen detection rates were compared. PNplus bin values and SOC descriptive or numerical quantities were evaluated for 1297 bacterial detections.

Results
13 samples (0.5%) gave invalid PNplus results. 3278 bacteria in PNplus were detected by PNplus and/or SOC. SOC detected 1878 bacteria (57.1%) compared to 3128 bacteria (95.8%) for PNplus (p=&lt; 0.0001). SOC detected 73 AB (70.9%) and 134 viruses (21.1%), PNplus detected 93 AB (90.3%) and 618 viruses (97.9%) (p=&lt; 0.0001). Mean number of analytes/sample detected by PNplus and SOC were 1.99 and 1.44, respectively. PNplus bin values were less than SOC, equal to SOC or greater than SOC in 5.9%, 25.4% and 69.6% of results, respectively. PNplus values were on average &gt; 1 log than SOC values (58.5% 1-2 logs; 11.0% 3-4 logs). PNplus identified 98.2% of MRSA and SOC 55.6%. All gram-negative resistance markers were detected at least once. PNplus and SOC results were fully concordant (positive or negative) or partially concordant for 49.1% and 26.4% of samples, respectively.

Conclusion
PNplus detected significantly more potential pathogens than SOC. Lack of routine SOC viral testing was a missed opportunity to define the cause of pneumonia. Semi-quantification may assist in understanding the significance of the pathogens detected. Pathogen and resistance marker detection in about 1 hr could dramatically impact antimicrobial use and enhance patient outcomes.

Disclosures
Christine C. Ginocchio, PhD, MT(ASCP), bioMerieux (Employee)bioMerieux (Employee, Shareholder) Barbara Mauerhofer, Pharmacist, bioMerieux (Employee) Cory Rindlisbacher, n/a, BioFire Diagnostics (Employee) Carolina Garcia, BS, bioMerieux (Employee)
650. Clinical Performance Evaluation of Virtuo Blood Culture System in a Tertiary Care Hospital
Authors: Chavez Miguel A , Munigala Satish , Burnham Carey-Ann , Yarbrough Melanie L , Warren David K 
Published: January 2021

Abstract

Background
Bloodstream infections are a major cause of morbidity and mortality. BACT/ALERT VIRTUO (VIRTUO) blood culture system is an automated, closed system used with resin-containing media which may enhance the growth of microorganisms. Our objective was to assess the real-world performance of the VIRTUO system.

Methods
We retrospectively reviewed all blood cultures performed between January-December 2018 (VersaTREK) and January-December 2019 (VIRTUO) at a 1250-bed academic medical center. Blood culture positivity rates, contamination rates, and time from collection to arrival in the laboratory were compared pre- versus post-VIRTUO implementation. Contamination was defined as a single blood culture with common skin microbiota.

Results
A total of 101803 blood cultures were performed during the study period: 48969 (48.1%) were processed with VersaTREK system and 52834 (51.9%) with VIRTUO system. A decreased median time from collection until arrival to the laboratory was seen post-implementation (2.0 pre- vs. 0.8 hours post-implementation, p&lt; 0.001). The positivity rate increased from 3987 (8.1%) pre-implementation to 6141 (11.6%) post-implementation (p &lt; 0.001) (Table and Figure). Staphylococcus aureus was the most frequently isolated species for both periods and had higher recovery rate with the VIRTUO system (717 (1.5%) pre- vs. 1764 (3.3%) post-implementation, p&lt; 0.001). Higher recovery rate was also noted for other Staphylococcus spp. in the post-implementation period (985 (2.0%) pre- vs. 1644 (3.1%) post-implementation, p&lt; 0.001). No difference in the organism recovery rate was noted for Streptococcus spp., Enterococcus faecium, E. faecalis, Pseudomonas aeruginosa, Enterobacterales, and Candida spp. The inpatient contamination rate was higher post-implementation (1.5% pre- vs. 1.9% post-implementation, p &lt; 0.001).
Comparison of blood culture positivity rate pre- vs. post-implementation, by culture location

Daily positivity rate for blood cultures processed at BJH during the study period

Conclusion
The VIRTUO system showed a higher rate of positive blood cultures compared to the VersaTREK system primarily from a higher detection of Staphylococcus spp. Further studies are needed to assess whether an increased rate of positive blood cultures is associated with changes in management and clinical outcomes.

Disclosures
All Authors: No reported disclosures