bluuebunny/crossref_metadata_2025_split huggingface dataset:
1223. The Impact of the COVID-19 Pandemic on the Prevalence of Multidrug-resistant Organisms in Veterans Affairs Nursing Homes
Authors: Sajib Monirul I , Ford Florence M , Psevdos George 
Published: December 2022

Abstract

Background
Multidrug-resistant organisms (MDRO) in long-term care facilities are prevalent and pose a major health concern for their residents. During the COVID-19 pandemic, infection control measures were justifiably heightened in every aspect of health care, including nursing homes. There are reports depicting decreasing prevalence of MDRO in hospital settings during the pandemic. We compared the prevalence of MDRO in our facility’s nursing homes in the two-year period before vs. the two years of the pandemic.

Methods
Northport Veterans Affairs Medical Center provides long-term nursing home care structured as community living centers including mental health and hospice care; a 139 total bed capacity. A retrospective review of culture data collected by infection control preventionists comparing the prevalence of MDROs between 1 March 2018 to 28 February 2022 was performed. Data included: Nasopharyngeal MRSA swabs, urine, wound, blood, sputum cultures, C. difficile toxin and PCR assays. MDRO included ESBL E. coli, K. pneumoniae, P. mirabilis, MDR Pseudomonas spp (resistance to 2/3 antibiotics: cefepime/piperacillin-tazobactam/ciprofloxacin), carbapenem-resistant Pseudomonas spp, and vancomycin-resistant Enterococcus spp.

Results
There were 75209 bed days of care from 1 March 2018 to 28 February 2020 vs. 77531 from 1 March 2020 to 28 February 2022. The MRSA rate per 1000 patient days decreased from 4.98 pre-COVID to 2.70 during-COVID, P &lt; 0.001. Similarly, there was a decrease in C. difficile 0.69 vs. 0.13, P&lt; 0.001, ESBL E. coli 0.53 vs. 0.51, P&lt; 0.001 and S. maltophilia (no cases during COVID). There was an increase in ESBL K. pneumoniae 0.51 vs. 0.63, P&lt; 0.001, MDR Pseudomonas 0.05 vs. 0.49, P&lt; 0.001, carbapenem-resistant Pseudomonas 0.026 vs. 0.077, P&lt; 0.001 and VRE 0.22 vs. 0.31, P&lt; 0.001. There were no Candida auris or Acinetobacter spp detected in the study period.
MDRO occurrences before and during COVID-19 pandemic

Conclusion
While increased awareness and implementation of infection control measures during the years of the COVID-19 pandemic led to decrease in certain infections in our nursing homes, like C. difficile, a surprising uptick in ESBL K. pneumoniae and MDR Pseudomonas was noted. This is a concerning trend that merits further study to identify molecular factors and increase stewardship efforts in diligent use of carbapenems.

Disclosures
All Authors: No reported disclosures.
1834. Evaluation of De-Escalation Options after Combination Daptomycin and Ceftaroline Therapy for Persistent MRSA Bacteremia
Authors: Carroll Ryan D , Brown Matthew L , Edwards William S , Stripling Joshua 
Published: December 2022

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia carries high mortality with limited treatment options. Studies over the last decade support glycolipopeptide and beta-lactam combination therapy with daptomycin (DAP) and ceftaroline (CFT) combination gaining prominence. While data supports de-escalation to monotherapy after bacteremia clearance it does not guide the choice of agent. With barriers including accessibility, cost, and tolerability of these agents, data is needed to optimize treatment. This study aims to evaluate de-escalation options after combination DAP/CFT therapy for persistent MRSA bacteremia.

Methods
A single-center, retrospective review of cases of persistent MRSA bacteremia (defined as greater than 72 hours on appropriate therapy) requiring escalation to DAP/CFT between 2014 and 2021 was performed. Details of bacteremia, source of infection, and comorbidities were assessed, and outcomes including recurrence of infection, infection-associated mortality, and tolerability were compared using exact Chi-square testing and univariant analysis.

Results
Sixty-six cases were identified of which 7 were de-escalated to vancomycin (VAN), 48 to DAP, 4 to CFT, and 7 continued DAP/CFT combination. Demographics and details of bacteremia such as prior anti-MRSA therapy, duration prior to DAP/CFT therapy, and source identification were similar between groups. Differences included higher rates of hemodialysis patients in the VAN group, higher rates of immunocompromised hosts in the DAP group, higher average Pitt bacteremia score in the DAP/CFT group, and lower rates of source control in the VAN group. Recurrence of infection (29% VAN, 13% DAP, 25% CFT) and infection-related mortality (14% VAN, 8% DAP) were higher in the VAN group (p=0.0452). In the DAP group 23% required change in therapy during their course. Univariant analysis assessing for confounding from comorbidities and source control yielded no significant associations.

Conclusion
This study is limited by small, uneven sample sizes but the results identify a trend of increased recurrence rates and mortality with de-escalation to VAN but tolerability concerns with DAP. More study is needed to guide clinical care and this data provides framework for future research.

Disclosures
All Authors: No reported disclosures.
2015. Challenges in Assessing Blood Stream Infection Clearance in Patients Receiving Extracorporeal Membrane Oxygenation
Authors: Frankford Stone A , Sobieszczyk Michal J , Markelz Ana E , Marcus Joseph E 
Published: December 2022

Abstract

Background
There is a limited published data on the treatment of blood stream infections (BSI) in patients receiving extracorporeal membrane oxygenation (ECMO). Traditionally, the management of only fungal and Gram-positive BSIs require follow-up blood cultures to document clearance. The presence of large retained cannulas in ECMO create concern for persistent bacteremia. This study investigates whether certain variables are predictive of blood stream infections with positive repeat cultures (BSIPRC) and if BSIPRC is associated with increased mortality.

Methods
All positive blood cultures from patients receiving ECMO at Brooke Army Medical Center identified between September 2012 and October 2021 were included in this study. Blood cultures were excluded if they were determined to be contaminants by the primary team. For each positive blood culture, charts were retrospectively reviewed. Date of clearance was defined as the first negative blood culture after a positive. BSIPRC was defined as re-isolation of the same organism on repeat blood cultures following an initial positive blood culture.

Results
A total of 60 patients and 87 BSI were investigated (38.5 BSI per 1000 ECMO days). Gram-positive (GP) organisms caused a majority of BSI (n=52, 60%) followed by Gram-negative (GN) (n=22, 25%) and fungal (n=13, 15%) infections. Of the 80 (92%) BSIs who had repeat blood cultures drawn, patients had BSIPRC in 35 (44%) of cases. There were no clinical features that differentiated patients with positive repeat cultures (Table). There was no difference in survival to discharge for patients with BSIPRC as compared to single day BSI (20 (58%) vs. 28 (63%), p=0.78). In 6 patients with BSIPRC with Gram-negative organisms, two (33%) died before clearance and five (83%) died before decannulation.
Characteristics of patients and all blood stream infections.

Conclusion
There were no clinical findings that differentiated patients with BSIPRC from those who had a single day of positivity. BSIPRC was associated with high mortality in patients with Gram-negative bacteremia. In the absence of clear predicative factors in demonstrating clearance of BSI, repeat blood cultures may be necessary. Future studies are needed to determine why Gram-negative BSIPRC are associated with a high mortality.

Disclosures
All Authors: No reported disclosures.
15. Forecasting the Monkeypox Outbreak: Using a SIR Epidemic Model
Authors: Mendes Neto Nilson N , Maia Marcio R G , Mendes Jessika Maia , Zacarkim Marcelo , Aronoff David M , Forgerini Fabricio L 
Published: December 2022

Abstract

Background
Monkeypox virus person-to-person transmission mostly occurs by personal contact with an infected individual or surface. We used the classical susceptible-infectious-removed (SIR) epidemic model (Figure 1) to forecast the virus spread in a simulated population.
Diagram of the SIR epidemic model

Methods
SIR model equations (ds/dt = −βsi; di/dt = βsi − µi; dr/dt = µi) were applied. We assumed an infection rate β = 9%; recovery rate µ = 100%; incubation period ranged from 4 to 21 days; length of a timestep = 15 days. Initially 150 infected individuals in a N= 10,000 population were organized in a lattice format (Figure 2) in which everyone has the same number of connections.
Schematic infection process: Initial condition with a susceptible population (white circles); we put a few infected individuals (red circles); the infection spreads through the nearest neighbors; then, the previously infected population gets recovered (blue circles) and the virus transmission continues.

Results
Around 45 days after the transmission started, we obtained a maximum incidence of 2.5% (Figure 3) of infection in the population. At this time, 0.5% of the infected cases will be recovered from monkeypox infection. If the fraction of initially infected cases is smaller than 150/10,000, our simulations show that the outbreak would end in the early days.
Numeric simulation of the SIR epidemic model in a lattice format and using β = 9%, µ = 100% and N = 10,000

Conclusion
Applying our results to the US population (335 million), almost 10 million people might be affected by monkeypox. Considering that infected people should be isolated for up to 21 days, this could lead to negative impacts on the economy as people would be out of their work environments. In addition, monkeypox could put even more pressure on the health system already worn out by the COVID-19 pandemic. This study might be used by health agencies to plan coordinated actions to contain the spread of monkeypox virus.

Disclosures
All Authors: No reported disclosures.
116. Potential Clinical Impact of Respiratory Syncytial Virus (RSV) Vaccination in Older Adults in the United States
Authors: Fust Kelly , Kohli Michele , Panozzo Catherine A , Weinstein Milton C , Buck Philip , Ghaswalla Parinaz 
Published: December 2022

Abstract

Background
RSV causes acute respiratory disease (ARD), including severe lower respiratory tract disease (LRTD) in older adults, which can lead to hospitalization and death. Currently, there are no vaccines approved to prevent RSV disease. This study estimated the potential clinical impact of a hypothetical RSV vaccine over a 1-year time horizon in older adults aged ≥ 60 years.

Methods
A decision-analytic model was developed (Figure 1). A strategy was used where the entire US population aged ≥ 60 years was given a single dose vaccine with an assumed efficacy of 75% against ARD, LRTD, and LRTD-hospitalizations and compared to a population who did not receive a vaccine. Given the uncertainty around RSV hospitalization rates, 2 base-case scenarios were created: (1) hospitalization rates that used RSV-specific claim codes and (2) hospitalization rates increased by 49% to account for underreporting in claims; Table 1 shows key inputs. One-way sensitivity analyses were used to assess the impact of specific parameter estimates.

Results
The vaccine would prevent 1.8 million and 0.6 million upper respiratory disease and LRTD cases, respectively; Figure 2 shows additional results for both base-case scenarios. The number needed to vaccinate (NNV) to prevent 1 LRTD case is 119; the NNV to prevent 1 LRTD hospitalization or death ranges from 792 to 1180 and 10,452 to 15,574, respectively. Sensitivity analyses indicate that results mainly depend on vaccine efficacy, and incidence of ARD and LRTD.

Conclusion
There is substantial US public health benefit associated with utilization of an effective RSV vaccine in individuals ≥ 60 years of age to reduce RSV-associated morbidity and mortality; however, the magnitude of impact depends on RSV epidemiology, which is still being defined for older adults. Several model parameters were based on assumptions, and robust evidence generation is needed including the efficacy of an RSV vaccine, which is an important consideration in assessing the impact of vaccination in this age group.

Disclosures
Kelly Fust, MS, Quadrant Health Economics Inc: Contractor at Quadrant Health Economics Inc who was funded by Moderna to perform this study Michele Kohli, PhD, Quadrant Health Economics Inc: Shareholder at Quadrant Health Economics Inc who was funded by Moderna to perform this study|Quadrant Health Economics Inc: Stocks/Bonds Catherine A. Panozzo, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Philip Buck, PhD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Parinaz Ghaswalla, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds.
218. A Phase 1 Study of the Single-Dose Safety, Tolerability, and Pharmacokinetics of the Beta-lactamase inhibitor Xeruborbactam Administered as the Isobutyryloxymethyl Oral Prodrug to Healthy Adult Subjects
Authors: Griffith David , Roberts Jason , Wallis Steven , Hernandez-Mitre Maria Patricia , Morgan Elizabeth , Dudley Michael , Loutit Jeff 
Published: December 2022

Abstract

Background
Xeruborbactam (XERU) is a member of a new class of cyclic boronic acid β-lactamase inhibitors with inhibitory activity against major members of Class A, B, C, and D beta-lactamases. This report describes the first safety and pharmacokinetic data following oral administration as the isobutyryloxymethyl prodrug in humans.

Methods
Forty-eight healthy subjects were enrolled into one of 6 cohorts of 8 subjects each in the single ascending doses (100, 200, 400, 600, 800, and 1000 mg). Subjects were randomly assigned with each cohort to XERU oral prodrug (n = 6), or placebo capsule (n = 2). Intensive plasma (total drug) and ultrafiltrate (free drug) sampling was obtained after dosing and assayed for QPX7831 and XERU content using validated HPLC/MS methods.

Results
XERU PK parameters following oral administration as the prodrug are shown in the table below. Compared to IV XERU doses (data not shown), XERU bioavailability is 90 - 100% orally bioavailable.
No subjects discontinued due to AEs and no SAEs were observed. There was no evidence of increasing numbers or severity of AEs with increasing dose. All AEs were mild in severity.

Conclusion
Orally administered XERU was safe and well tolerated at all doses tested. Plasma XERU AUC and Cmax increased with increasing dose. XERU exposures (24h free AUC) exceed the predicted PK-PD parameter for stasis with once-daily doses of 400 mg or higher and exceed the PK-PD parameter for 1-log of bacterial killing once daily doses of 800 mg or higher. XERU, administered as an oral prodrug, has plasma PK properties that support once-daily administration.

Disclosures
David Griffith, n/a, Qpex Biopharma: Employee Jason Roberts, BPharm(Hons), PhD, FSHP, FISAC, British Society of Chemotherapy: Grant/Research Support|Cipla: Honoraria|Gilead: Advisor/Consultant|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Board Member|Pfizer: Honoraria|Qpex: Grant/Research Support|Sandoz: Board Member|Summit: Advisor/Consultant|Wolters Kluwer: Advisor/Consultant Elizabeth Morgan, n/a, Qpex Biopharma: Employee Michael Dudley, n/a, ArrePath: Board Member|Qpex Biopharma: Board Member|Qpex Biopharma: Employee Jeff Loutit, MBChB, Qpex Biopharma: Employee.
306. Development a Predictive Score for Severe Coronavirus Disease 2019 (COVID-19) from High Risk Factor of Patient Described by Thai Government Policy
Authors: Noopetch Preudtipong , Benchamanon Rutporn , Kongsuwan Samerjan , Chai-adisaksopha Chatree 
Published: December 2022

Abstract

Background
Thai government had a policy defined population groups that are at risk of severe COVID-19 infection. It is called “608 group” consisting of age more than 60 years old, obesity, diabetes mellitus, cancer, cerebrovascular disease, respiratory disease, chronic kidney disease, HIV infection, and pregnancy. But no study has evaluated performance of this policy. We aimed to develop parameter risk-based scoring system from Thai policy for diagnosis of severe COVID-19 infection.

Methods
A study was carried out in 11,677 patients with confirmed COVID-19 infection were admitted to Hatyai hospital, Songkhla, Thailand from 1 April 2021 to 31 December 2021. Patients were categorized to severe COVID-19 infection if their oxygen saturation less than 94% or need oxygen supplement. Multivariable logistic regression was used to explore for predictors. The logistic coefficients were transformed to risk-based scoring system.

Results
A total of 11,677 patients were included in analysis and predictive model development, 1036 (8.88%) patients were severe COVID-19 infection, and 10,631 (91.12%) patients were non-severe COVID-19 infection. Age more than 60 years old, obesity, diabetes, cancer, cerebrovascular disease, respiratory disease, chronic kidney disease, HIV infection, and pregnancy were used for derivation of the scoring system. The score-based model showed area under ROC of 0.81 (95%CI 0.79 – 0.82). The scoring system ranged from 0 to 40 was classified into 3 subcategories for clinical practicability. The sensitivity and specificity for predictive of severe COVID-19 were 81.18% and 69.83% for low risk patient, 70.56% and 80.79% in moderate risk patient, and 54.92% and 89.81% in high risk patient.

Conclusion
This simplified risk-based scoring system for prediction severe COVID-19 disease could aid general physicians or internist in evaluation and triage of patients who present with COVID-19 infection and help physicians in management and prioritization of patients in outbreak situation.

Disclosures
All Authors: No reported disclosures.
489. Bile Acid Concentrations in Healthy Volunteers Receiving Oral Omadacycline or Vancomycin
Authors: Jo Jinhee , Hu Chenlin , Wang Weiqun , Gonzales-Luna Anne J , Lancaster Chris , Garey Kevin W 
Published: December 2022

Abstract

Background
Microbiome disruption associated with Clostridioides difficile infection (CDI) includes reduced metabolism of primary to secondary bile acids leading to increased likelihood of C. difficile germination and CDI recurrence. Omadacycline has potent in vitro activity against C. difficile but its effect on the microbiome is unknown. The purpose of this study was to assess changes in bile acid concentrations in healthy volunteers given omadacycline compared to vancomycin, the most common antibiotic used to treat CDI.

Methods
As part of an ongoing healthy volunteer study of adults between 18 and 40 years, subjects received a 10-day course of oral omadacycline or vancomycin. Stool samples were collected and bile acids were extracted and quantified via targeted liquid chromatography-mass spectrometry (LC-MS). For this analysis, samples collected at the end of antibiotic therapy (day 9-10) were analyzed for primary and secondary bile acids. Results were compared and visualized using R (ggplot2).

Results
Between October 2020 and December 2021, 16 healthy volunteers aged 26 ± 5 years (male: 69%; Caucasian: 31%; mean body mass index: 23.6 ± 3.8 kg/m2) were enrolled. Concentrations of primary bile acids (cholic acid and chenodeoxycholic acid) were higher in patients receiving oral vancomycin than those receiving omadacycline (Table 1). Secondary bile acids were higher in the omadacycline arm compared to vancomycin. Secondary:primary bile ratio was higher for omadacycline (0.43) than vancomycin (0.03).

Conclusion
Omadacycline preserved bile acid homeostasis in the gut to a higher extent that vancomycin, suggesting reduced microbiome dysbiosis. With potent in vitro C. difficile activity, availability as an oral and IV formulations, and favorable microbiome properties, further development of omadacycline for the treatment of CDI is warranted.

Disclosures
Kevin W. Garey, PharmD, MS, Acurx Pharmaceuticals: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Seres Therapeutics: Grant/Research Support|Summit Pharmaceuticals: Grant/Research Support.
500. Impact of an iron chelator on in vitro and in vivo growth of A. baumannii
Authors: Eales Brianna , Bai Bing , Tam Vincent 
Published: December 2022

Abstract

Background
Acinetobacter baumannii (AB) has become multidrug-resistant in recent years and currently there is no consensus on the optimal treatment for these infections. To combat this urgent threat, novel treatment options are needed to minimize spread and lower mortality rates. Nutrient metals (e.g., iron) are essential to the metabolic functions of AB. If the bioavailability of essential nutrients is restricted, this can cause a bacterial stress response and alter their ability to multiply.

Methods
The objective of the study was to examine the impact of iron chelation on the growth of AB in vitro and in vivo. MDR AB bloodstream isolates (n=4) were recovered from unique patients between 2011 and 2018. Clonal diversity was ascertained by Fourier Transform Infrared Spectroscopy. In vitro bacterial densities were measured longitudinally over 20-hours to determine the growth profile. Isolates were started at a baseline concentration of approximately 5.5 log CFU/mL in tryptic soy broth. Variable amounts of an iron chelating agent (deferiprone, 0.2-2mM) were added to create a concentration gradient. Galleria mellonella larvae (100-150mg) were inoculated with approximately 5 log CFU of an isolate, with and without deferiprone (10mM). Quantitative culture was used to ascertain the bacterial burden of aggregate larvae (n=10) immediately and 4h post infection. Additional infected larvae (n=20 in each group) were incubated at 35°C and monitored hourly for 24h.

Results
Time to mortality was compared using Kaplan-Meier survival analysis and log-rank test. Increasing concentrations of the chelating agent caused a transient and concentration-dependent hindrance of in vitro bacterial growth, compared to the no-treatment group. Bacterial burden immediately post-infection of the control and treatment group were comparable at 6.4 log CFU/g. After 4 hours the bacterial burden was much higher in the control group than the treatment group, 8.7 and 6.7 log CFU/g respectively. A trend of delayed mortality was shown in the iron chelator group (median survival 6.5 vs 10 hours, p=0.15).

Conclusion
These results support that micro-nutrient limitation has the potential to be a novel approach for treating high-risk infections due to MDR AB. Future studies are warranted to further define its optimal place in therapy.

Disclosures
All Authors: No reported disclosures.