bluuebunny/crossref_metadata_2025_split huggingface dataset:
402. Risk Factors for the Development of Clostridioides difficile Infection in Patients Colonized with Clostridioides difficile
Authors: Clement Josh , Barlingay Gauri , Donnelley Monica , Crabtree Scott 
Published: December 2022

Abstract

Background
Asymptomatic patients colonized with Clostridioides difficile are at risk of progressing to C. difficile infection (CDI), but the risk factors associated with progression are poorly defined. The objectives of this study were to identify the prevalence and risk factors to progression of hospital-onset CDI (HO-CDI) among colonized patients.

Methods
This was a retrospective cohort study conducted at a large academic medical center. Patients were included if they were ≥ 18 years of age and colonized with C. difficile, detected via polymerase chain reaction (PCR) on a rectal swab collected on admission from 2017 to 2020. Patients were excluded if they had prior CDI, CDI symptoms on admission, neutropenia, prior rectal surgery, or were hospitalized for less than 24 hours. CDI toxin positive patients were matched 1:3 to CDI negative patients using PCR colonization test date. The primary endpoints were the prevalence of HO-CDI and the risk factors for progression to HO-CDI. Descriptive analyses were used to describe the population and univariate analysis was used to determine risk factors associated with HO-CDI.

Results
A total of 2,150 patients were colonized with C. difficile; 109 CDI toxin positive patients were matched to 327 CDI toxin negative patients. 134 patients were included and 3.2% (69/2150) developed HO-CDI. The median age was 64 and 68 patients (50.7%) were male. Malignancy (OR 2.89, 95% CI: 1.24-6.75; P = 0.01), hospitalization within one month (OR 2.2, 95% CI: 1.1-4.38; P = 0.03), antibiotic use within one month (OR 3.23, 95% CI: 1.59-6.56; P = 0.001), antibiotic use within three months (OR 2.16, 95% CI: 1.07-4.35; P = 0.03), intensive care unit (ICU) admission (OR 5.14, 95% CI: 2.47-10.73; P &lt; 0.0001), immunosuppressant use (OR 3.33, 95% CI: 1.14-9.78; P = 0.03), and use of a third generation cephalosporin within three months (OR 4.5, 95% CI: 1.12-18.13; P = 0.03) were associated with HO-CDI.

Conclusion
Progression to HO-CDI was uncommon among colonized patients at our institution. This data suggests that in hospitalized patients colonized with C. difficile, malignancy, hospitalization within one month, antibiotic use within one or three months, ICU admission, receipt of immunosuppressants, and use of a third generation cephalosporin within three months are associated with HO-CDI.

Disclosures
All Authors: No reported disclosures.
429. Identifying Barriers to Compliance with a Universal Inpatient Protocol for Staphylococcus aureus Nasal Decolonization with Povidone-Iodine
Authors: Talbot Thomas R , Harris Bryan D , DeVault Mary , Stern Rebecca A 
Published: December 2022

Abstract

Background
Intranasal povidone-iodine (PI) is a recommended strategy for universal decolonization in high-risk patients (ICU and those with central venous or midline catheters) to reduce hospital-associated Staphylococcal infections. Few studies have evaluated implementation challenges and barriers to successful performance of inpatient intranasal decolonization programs.

Methods
We surveyed adult acute care unit nurses at an academic medical center in March 2022, approximately 14 months after implementation of a universal decolonization standard operating procedure (SOP). The anonymous, voluntary REDCap® survey evaluated domains focused on patient identification, education, training, resources, application, and patient acceptance using Likert scale ratings.

Results
Among 248 respondents, most were new to nursing (54.4% with 0-4 years of experience) and worked in non-ICU units (61.5%). Only 60.5% reported receiving training on how to perform intranasal PI (hands-on 48.6%, computer/electronic module 25.7%, both 20.9%). Nurses who received training indicated moderate to strong confidence in their ability to perform intranasal PI decolonization (89.2%). A majority cited a good understanding of the rationale for use and identified patients appropriately. Low rates were reported for performing decolonization per the SOP (49%), with barriers including inadequate supplies (35.1%), lack of a readily available copy of the SOP (69%), difficulty swabbing with nasal devices in place (41.5%) and time constraints from other patient duties. Nurses perceived that only 49.2% of patients had a moderate or strong understanding of why PI decolonization was performed, and most were unwilling to undergo intranasal PI (59.1%). Other issues included tracking PI application within the electronic medical record (EMR), limited nurse knowledge of PI effectiveness, patient refusal despite education, and overall frontline personnel burnout.

Conclusion
Gaps in nursing and patient education should be prioritized during and after implementation to improve fidelity, particularly with frontline burnout from COVID-19. Streamlined tracking and ordering of PI on the EMR may ease nursing workflow.

Disclosures
Thomas R. Talbot, III, MD, MPH, OmniSolve: Board Member.
436. Paid sick leave among U.S. healthcare personnel, April 2021
Authors: de Perio Marie , Srivastav Anup , Razzaghi Hilda , Laney Anthony , Black Carla 
Published: December 2022

Abstract

Background
Healthcare personnel (HCP) are at risk for acquiring and transmitting coronavirus disease 2019 (COVID-19), influenza, and other respiratory infections in the workplace. An important strategy to prevent workplace transmission, paid sick leave benefits allow workers to stay home and visit a healthcare provider when ill. Our objectives were to quantify the percentage of HCP reporting paid sick leave, identify differences across occupations and settings, and determine factors associated with having paid sick leave.

Methods
In a national nonprobability Internet panel survey of HCP in April 2021, respondents were asked, “Does your employer offer paid sick leave?” We weighted responses to the U.S. HCP population by age, sex, race/ethnicity, work setting, and census region. We calculated the weighted percentage of HCP who reported paid sick leave by occupation, healthcare setting, and type of employment. Using multivariable logistic regression, we identified factors associated with having paid sick leave (i.e. an adjusted prevalence ratio (aPR) with a 95% confidence interval that excludes 1).

Results
In April 2021, 71.4% of 1,652 responding HCP reported having paid sick leave, a slight increase from 68.1% in April 2020. The percentage of HCP reporting paid sick leave varied by occupation, ranging from 54.3% (physicians) to 88.8% (nurse practitioners/physician assistants), and by work setting, ranging from 59.7% (“other” clinical settings) to 82.4% (hospitals). In multivariable analyses, factors associated with having paid sick leave included age between 30–44 years (aPR:1.20) and 45–59 years (aPR:1.22) and male sex (aPR:1.19). HCP working as physicians (aPR:0.74), as contract employees (aPR:0.71), and those working in the Midwest (aPR:0.78) and South (aPR:0.87) regions and in rural settings (aPR:0.86) were less likely to report having paid sick leave.

Conclusion
The majority of HCP from all occupational groups and healthcare settings reported having paid sick leave. However, differences by age, sex, occupation, type of work arrangement, and region exist and highlight disparities. Increasing HCP access to paid sick leave may decrease presenteeism and subsequent transmission of infectious diseases in healthcare settings.

Disclosures
All Authors: No reported disclosures.
437. A Single-Center Experience of Solid versus Hematologic Malignancies in People Living with HIV
Authors: Daoud Nour A , Bhuiyan Mohammad Alfrad Nobel , Koppada Satya , Alam Mohammad , Malek Alexandre E 
Published: December 2022

Abstract

Background
People living with HIV (PLWH) have an increased risk of cancer, including AIDS-defining and non-AIDS-defining malignancies. Some of the contributing factors are related to the high-risk lifestyle choices, but the introduction of HAART has reduced the incidence of AIDS-defining cancers.

Methods
We conducted a retrospective study of PLWH who were diagnosed with cancer between November 2019 and March 2022. We identified 60 patients who had HIV infection prior to the diagnosis (dg) of cancer or concurrently diagnosed with cancer. We evaluated patient’s characteristics, CD4 T cell counts, HIV viral load, adherence to HAART, solid and hematologic (HM) malignancies.

Results
Sixty pts were included in the analysis. The median age was 49.50 (range, 21-76 yrs) and 48 pts (80%) were male. The majority were African Americans (78.3%). Around 75% of pts were smokers, 35% of pts use alcohol, and 33.3% use illicit drugs. Cancer types were non-Hodgkin lymphoma (NHL) (11 pts, 18.3%), skin cancer (8 pts, 13.3%), Kaposi sarcoma (KS) (7 pts, 11.7%), prostate cancer (7 pts, 11.7%), head and neck cancer (5 pts, 8.3%), breast cancer (4 pts, 6.7%), Hodgkin lymphoma, leukemia, and lung cancer with same percentage each (3 pts, 5%), colorectal cancer (2 pts, 3.3%), and miscellaneous solid tumors (7 pts, 11.7%). AIDS-defining cancers were identified in 28.3% of pts. The median time between HIV and cancer dg was 8 years (range, 0-31 yrs). Eight pts (13.3%) were diagnosed with HIV and cancer at the same time [NHL (3 pts), myeloid leukemia (1 pt), and solid tumors different than cervical cancer (4 pts)]. A group of 43 pts (71.7%) had solid tumors were compared with 17 patients (28.3%) had HM. There were no differences between the two groups regarding gender, sexual orientation, smoking history, medical comorbidities, time between HIV and cancer dg. Pts with HM were younger (P-value of 0.05), and the rate of alcohol use was higher in pts with solid tumors (P-value, 0.003). HIV viral load &gt; 200 copies/ml was higher in HM (75%) than solid tumors (44.1%) with P-value of 0.06 and the adherence rate to HAART was higher in pts with solid tumors (67.6%) compared to HM (38.4%) with a P-value of 0.1, prior to cancer dg.

Conclusion
PLWH with HM are more likely to be younger, non-adherent to HAART, and have higher HIV viremia compared to pts with solid tumors.

Disclosures
All Authors: No reported disclosures.
465. A Multifaceted and Multi-Institutional Analysis of the COVID19-Associated Mucormycosis Outbreak in the Delhi Area Indicates the Simultaneous Convergence of Multiple Risk Factors
Authors: Chowdhary Anuradha , Wurster Sebastian , Gupta Nitesh , Mohabir Jason , Tatavarthy Shashidhar , Mittal Vikas , Sharma Brijesh , Jiang Ying , Cuomo Christina , Kontoyiannis Dimiitrios P 
Published: December 2022

Abstract

Background
A major outbreak of COVID19-associated mucormycosis (CAM) in India in spring 2021 aggravated the death toll of COVID19. As the causes of that CAM outbreak remain unclear, we performed a multifaceted study of host, pathogen, environmental, and heath care-related factors in adult CAM patients (pts) in the metropolitan New Delhi area.

Methods
We reviewed the records of all pts diagnosed with culture- or biopsy-proven CAM at 7 hospitals in the New Delhi area (April 1 – June 30, 2021). We used a multivariate logistic regression model to compare clinical characteristics of either all CAM cases (analysis 1, n = 50) or only pts with CAM after moderate or severe COVID19 (analysis 2, n = 31). As controls for both analyses, we used 69 COVID19-hospitalized contemporary pts. Selected hospital fomites were cultured for Mucorales. Additionally, we compared meteorological data and fungal spore concentrations in outdoor air before the CAM outbreak (January-March 2021) and during the outbreak (April-June 2021). Mucorales isolates from CAM pts were identified by MALDI-TOF-MS and ITS sequencing. A subset of 15 isolates underwent whole genome sequencing (WGS).

Results
Risk factors for CAM in both analyses were newly diagnosed diabetes mellitus (odds ratio [OR] 8.26/5.67) and active cancer (OR 5.98/5.68) (Figure 1). Supplemental oxygen for COVID19 was associated with a lower CAM risk in both analyses (OR 0.13/0.17). Another significant CAM risk predictor identified only in analysis 1 was severe COVID19 (WHO score ≥ 6, OR 4.09), while remdesivir therapy (OR 0.40) and ICU admission for COVID19 were protective (OR 0.41) (Figure 1). No Mucorales were cultured from hospital fomites. The CAM incidence peak coincided with a significant uptick in environmental spore concentrations but was not linked to specific meteorological factors. Rhizopus was the predominant Mucorales genus (64%) identified by MALDI-TOF-MS and ITS sequencing; WGS found no clonal population of isolates but detected 2 cases of the rare pathogen Lichtheimia ornata. Figure 1

Conclusion
An intersection of host, environmental, pathogen and healthcare-related factors might have contributed to the emergence of CAM. Surrogates of access to advanced treatment of COVID19 were associated with lower CAM risk.

Disclosures
Dimiitrios P. Kontoyiannis, MD, ScD, PhD (hon), AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Merck: Advisor/Consultant.
483. Use of Terbinafine in Combination with Other Systemic Anti-fungal Agents As Treatment for Invasive Mold Infections. Experience from A National Cancer Institute Designated Cancer Center.
Authors: Ajayi Eloho , Sikora Anna , Klinkova Olga , Cozzini Lisa , Pasikhova Yanina , Quilitz Rod , Morrison Austin R , Baluch Aliyah 
Published: December 2022

Abstract

Background
The severely Immunocompromised are at an increased risk of fatal infection caused by invasive molds. Amphotericin B and triazole agents with anti-mold activity are commonly used in treating invasive mold infections. There is some data from in-vitro experiments to suggest an enhanced killing of some molds when terbinafine is used in combination with certain azoles or amphotericin B. At our center, terbinafine is occasionally used in combination with other systemic anti-fungal agents in treating severely immunocompromised patients with invasive mold infections.

Methods
The study was a retrospective review of electronic medical records. Sixty-four patients treated for culture confirmed infection with mold isolates at the Moffitt Cancer Center from 1/1/2015 to 6/1/2021 were included in this study. There were 2 treatment groups: Group A comprised of those treated with a terbinafine containing regimen and Group B comprised of patients that were not treated with a terbinafine containing regimen.

Results
Treatment group A: Comprised of 14 patients. Twenty-nine percent (4/14) had skin/soft tissue infections, 21% (3/14) had rhinosinusitis, 21% (3/14) had pulmonary infections and 4 patients (29%) had disseminated infection. Thirty-six percent (5/14) were discharged with treatment response, 57% (8/14) did not respond to treatment or died due to the invasive mold infection and 7% (1/14) died as a result of malignancy.
Treatment group B: Had 50 patients. thirty-eight percent (19/50) had pulmonary infections, 28% (14/50) with skin/soft tissue infections, 16% (8/50) had rhinosinusitis, 2% (1/50) were diagnosed with central nervous system infection, 2% (1/50) had gastrointestinal infection, 14% (7/50) had an unclear source of infection. Forty-eight percent (24/50) were discharged with treatment response, 42% (21/50) had treatment failure or died due to the invasive mold infection and 10% (5/50) died as a result of malignancy. Table 1Figure 1

Conclusion
There was no statistically significant improvement in outcome observed in this study when terbinafine was used in addition to other systemic anti-fungal medications as treatment of invasive mold infections. There is a need for larger studies to determine if terbinafine has a role in the treatment of invasive mold infections.

Disclosures
All Authors: No reported disclosures.
485. A hypermutator strain of Pseudomonas aeruginosa in a COVID-19 patient with ventilator-associated pneumonia
Authors: Nozick Sophia , Ozer Egon A , Medernach Rachel , Mills Jori , Wunderink Richard , Hauser Alan R 
Published: December 2022

Abstract

Background
P. aeruginosa is a cause of hospital-acquired and ventilator-associated pneumonia. Hypermutator P. aeruginosa strains have been described in patients with cystic fibrosis and chronic respiratory infections but are rare in patients with acute P. aeruginosa infection. This case describes a hypermutator strain of P. aeruginosa found in a patient with COVID-19-associated acute respiratory distress syndrome (ARDS).

Methods
Serial respiratory and blood cultures were collected. Short-read sequencing libraries were prepared using the Illumina Nextera XT kit, and whole-genome sequencing was performed using the Illumina NextSeq platform. Long-read sequencing libraries were prepared from unsheared genomic DNA using ligation sequencing kit SQK-LSK109 and sequenced on the Oxford MinION platform. Single nucleotide variants were identified by aligning reads from each isolate to the complete genome of the first available clinical isolate. Hypermutator assays were performed by measuring the mutation frequency rate for rifampin resistance. Antibiotic minimal inhibitory concentrations (MICs) were performed. Growth curves were performed with a starting OD600 of 0.1 with measurements taken every 30 minutes for 24 hours.

Results
Seventeen respiratory and five blood isolates were obtained throughout 62 days of hospitalization. Fourteen of the 22 isolates exhibited hypermutator phenotypes by rifampin resistance assays, which demonstrated rapid accumulation of mutations. All five bloodstream isolates were hypermutators. MIC testing noted increased resistance to aminoglycosides, fluoroquinolones, and aztreonam in the hypermutator isolates. All bloodstream isolates descended from a single progenitor noted on whole-genome sequencing. Each hypermutator strain contained a mutation in the mismatch repair gene mutL, previously associated with the hypermutator phenotype.
Genetic Tree of Patient Isolates
The genetic tree highlights hypermutator versus non-hypermutator single nucleotide variants

Conclusion
This case was notable for multiple isolates of hypermutator P. aeruginosa that persisted over weeks. The patient’s COVID-19 infection and acute respiratory distress syndrome may have facilitated persistence of the P. aeruginosa lineage, allowing a hypermutator lineage to emerge.

Disclosures
All Authors: No reported disclosures.
487. Analysis of the Association between Specific Antibody Response against Respiratory Syncytial Virus Fusion Protein Conformations and Life-Threatening Infection in Previously Healthy Infants
Authors: Bonnin Florencia A , Talarico Laura B , Phung Emily , Kumar Azad , Ferolla Fausto M , Byrne Alana B , Acosta Patricio L , Toledano Analía , Caratozzolo Ana , Contrini María M , Graham Barney S , Ruckwardt Tracy , López Eduardo L 
Published: December 2022

Abstract

Background
Specific humoral response against pre-fusion (pre-F) conformation of respiratory syncytial virus (RSV) F protein has been proposed to play a role against severe infection. We aimed to analyze the association between serum IgG titers against pre-F and post-fusion (post-F) conformations of RSV F protein and life-threatening RSV disease (LTD) in previously healthy infants.

Methods
Prospective cohort study including previously healthy infants &lt; 12 months, hospitalized with a first RSV infection, in 2017-2019. Patients were defined to have LTD when required intensive care and ventilatory support. Pre-F exclusive and post-F-specific antibody responses were determined by post-F competition and non-competitive immunoassays, respectively, and neutralizing activity was measured by plaque reduction neutralization test. Viral load (VL) was assessed by qRT-PCR from nasopharyngeal aspirates collected on admission. Serum samples were collected within 72 h from admission and in convalescence (between 14 to 60 days).

Results
Seventy-five patients were included, median age 3 months, 60% (n=45) were males; 21 patients developed LTD. Importantly, acute and convalescent post-F and pre-F exclusive IgG titers did not associate with LTD (Fig 1). There was a positive correlation between neutralizing antibody titers and pre-F exclusive IgG titers (p=0.016). Post-F and pre-F exclusive IgG titers negatively correlated with age in acute phase (p&lt; 0.0001 and p= 0.0009). In acute phase, post-F and pre-F exclusive IgG titers were higher in patients ≤ 2 months (Fig 2). Patients &gt; 2 months increased post-F and pre-F exclusive IgG titers in convalescence. Additionally, post-F and pre-F exclusive titers did not correlate with VL, and VL was not related to LTD.

Conclusion
-Pre-F exclusive and post-F IgG titers did not associate with LTD, even though pre-F exclusive IgG correlated with neutralizing antibody titers.
-Infants under two months of age developed a lower humoral response, likely due to an interference by maternal antibodies and/or immunological immaturity.
-These findings highlight the importance of fully characterizing the immune response against RSV and its association with disease severity for the development of preventive strategies.

Disclosures
Barney S. Graham, MD, PhD, BSG: BSG is an inventor on patents for the stabilization of the RSV F protein (WO2014160463A1, Prefusion RSV F proteins and their use).|National Institutes of Health: Inventor on patents for RSV vaccines|National Institutes of Health: inventor on patents for measles and other paramyxovirus vaccines.