bluuebunny/crossref_metadata_2025_split huggingface dataset:
782. Employing the 4MAT model of instruction to develop a novel interactive virtual geriatrics course for interprofessional HIV clinicians
Authors: Howell Aroonsiri , Ross Amelia , Javier Noelle Marie , Appelbaum Jonathan , Dozier Laurie L 
Published: November 2023

Abstract

Background
With the advent of antiretroviral therapy, people with HIV (PWH) are living longer and experiencing geriatric syndromes. Many older PWH are cared for by teams of interprofessional HIV clinicians, most of whom lack geriatrics training. We aimed to increase geriatrics knowledge and preparedness to care for older PWH among interprofessional HIV clinicians through a unique application of the 4MAT model.

Methods
From July 2020-August 2021, we enrolled physicians, nurse practitioners, physician assistants, and pharmacists in a virtual 7-hour course. Learners were assessed by pre- and post-course quizzes and self-reported preparedness to care for older PWH. There were 75 learners (44% physicians, 31% nurse practitioners/physician assistants, 24% pharmacists).

Results
Before the course, 49.3% of learners felt prepared to care for older PWH vs. 93.7% post-course (p&lt; 0.00). Average quiz scores improved on all topics (p&lt; 0.00).

Conclusion
Our course is a unique application of the 4MAT model that improved geriatrics knowledge and clinical preparedness across a wide array of interprofessional HIV clinicians.

Disclosures
All Authors: No reported disclosures
783. Knowledge of and attitude toward antibiotic use and resistance among medical students from a Thai public university
Authors: Sae-li Porntita , Hanvivattanakul Sirashat , Nana Ruj , Khawcharoenporn Thana 
Published: November 2023

Abstract

Background
Assessment of knowledge of and attitude toward antibiotic use and resistance is essential for developing interventions that promote appropriate antibiotic use among medical students.

Methods
An online survey study was conducted among preclinical- and clinical-year medical students of academic year 2022, at a Thai public university from January to April 2023. The knowledge score was calculated based on the correct responses to the 15 provided statements and attitudes were assessed by the 5 Likert scale.

Results
Of the 313 participating students, 202 (65%) were in preclinical years, 111 (35%) were in clinical years, 44% were male, median grade point average was 3.5, and 71% reported history of internet searching for antibiotics. The median knowledge score about antibiotic use and resistance was higher among clinical-year students than preclinical-year students (12 vs. 9; p&lt; 0.001). Less than 50% of preclinical-year students correctly responded to statements “There is no evidence of antibiotic resistance for gonorrhea” and “Antibiotic resistance can be transmitted from animals or humans to humans”, while less than 50% of both preclinical- and clinical years correctly responded to statements “Use of antibiotics in animals can lead to antibiotic resistance in humans”. Preclinical-year students were more likely than clinical-year students to agree that antibiotic resistance should be taught early in high schools and believe that we can always discover and develop new antibiotics, while clinical-year students were less-likely to agree that the Faculty of Medicine provided enough knowledge about antibiotic use and resistance during their study (P&lt; 0.05). In multivariable linear regression analysis, factors associated with higher knowledge scores included higher academic year (P&lt; 0.001), monthly household income ≥ $USD 3,000 (P=0.04), and high level of English proficiency (P=0.04).

Conclusion
Provision of additional knowledge of and improving attitude toward antibiotic use and resistance were required and tailored based on the students’ academic years. The identified factors associated with knowledge score should be considered for implementing interventions to improve knowledge of and attitude toward antibiotic use and resistance.

Disclosures
All Authors: No reported disclosures
815. False Negative BioFire FilmArray Meningitis/Encephalitis Multiplex PCR Assay in Cryptococcal meningitis: A Single Center Analysis
Authors: Dang-Orita Nancy , Chan-Golston Alec M , Mitchell Marilyn , Sivasubramanian Geetha 
Published: November 2023

Abstract

Background
Cryptococcal meningoencephalitis (CM) remains a devastating infection in immunocompromised patients. Diagnosis is made by using cerebrospinal fluid (CSF) and serum cryptococcal antigen (CrAg) detection by lateral flow assay (LFA), fungal cultures and more recently a multiplex polymerase chain reaction (PCR) panel. The BioFire® FilmArray® meningitis/encephalitis (FA-ME) multiplex PCR assay targets 14 pathogens and is a quick tool for evaluating patients with meningitis/encephalitis (ME). However, false negative FA-ME results have been reported in patients with CM. We performed a retrospective analysis to study the performance of the FA-ME PCR assay in comparison to other available methods in the diagnosis of CM.

Methods
We identified patients with CM in our center between 2017 and 2022 using ICD9 and 10 codes (Figure 1). Data pertinent to demographics, clinical features, diagnostics of CM was collected. We included only the first spinal fluid test results that were done as part of diagnostic workup for ME for the analysis.

Flowchart of patients included and excluded in the study of BioFire FilmArray Meningitis/Encephalitis Multiplex PCR in the diagnosis of Cryptococcal Meningitis

Results
Forty-five patients with CM met the inclusion criteria (Table 1). Of these, 12/45 had discordant false negative FA-ME multiplex PCR. Seven of the 12 patients tested falsely negative during their first episode of CM and four of them were on prior antifungals (Table 2). Thirty-six of 45 (80%) reported this was their first episode of CM. Of those, 19.44% (7 of 36) had false negative FA-ME multiplex PCR. This was found to be significantly different than the percentage with false negative FA-ME multiplex PCR in the recurrence/relapse group (55.56%; 5 of 9) using Fisher’s Exact Test (p = 0.04275). Using the Wilcoxon rank-sum test, the median of the fungal burden is significantly different between the concordant and discordant cases with the median CSF Ag titer lower in patients with false negative FA-ME results (p = 0.0016).

Conclusion
BioFire FA-ME multiplex assay may be falsely negative in patients with cryptococcal meningitis even during their first episode. Although the chances of false negative tests are higher with lower fungal burden and in cases of relapses, caution must be used in interpreting the results. Serum CrAg was underutilized as a diagnostic aid in our patients and should be considered along with cultures and CSF CrAg when lumbar puncture is delayed.

Disclosures
All Authors: No reported disclosures
817. Caspofungin versus Anidulafungin in Patients with Candidemia: Retrospective Comparative Study
Authors: Elajez Reem , Bakdach Dana , Al Balushi Sara , Abdallah Tasneem , Zaqout Ahmed , Alattar Rand , Awouda Waleed , Wilson Godwin , Alsoub Hussam Abdelrahman 
Published: November 2023

Abstract

Background
Echinocandins are recommended as initial treatment for candidemia. The safety and efficacy of both anidulafungin and caspofungin are well established, yet; no direct comparison was made pertaining to their efficacy and safety. This was a retrospective study to compare efficacy and safety of anidulafungin versus caspofungin in patients with candidemia.

Methods
All adult patients with candidemia who were treated with either anidulafungin or caspofungin for ≥ 5 days, over a period of 6 years were retrospectively included. Baseline demographics, infection characteristics and patient courses were assessed. The primary end point was global response defined as clinical and microbiological success at the end of treatment duration.

Results
A total of 171 patients received either anidulafungin (n = 135) or caspofungin (n = 36) based on physician preference. The most common isolated candida species were candida glabrata (31.6%) followed by candida albicans (25.1%). Around 6% had chronic liver disease, and source control (mainly catheter removal) was achieved in 91.8%. Baseline characteristics were comparable between the two groups suggesting similar risks and treatment response. Response rates were similar among both groups with the primary outcome of global response being not significantly different (50% for caspofungin group vs 65.2% for anidulafungin, p=0.666). Similarly, no differences between the two groups were observed in terms of 90-day all-cause mortality (p=0.405) and hepatic safety profile defined as elevated liver function tests ≥ 3 times from baseline (p=0.521)

Conclusion
Our data suggested that among patients with candidemia, there was no difference between anidulafungin and caspofungin for the primary endpoint of global response. Both studied echinocandins had similar rate of 90-day all-cause mortality and liver safety profile.

Disclosures
All Authors: No reported disclosures
820. Clinical Outcomes in Patients with Candidemia with and without Infectious Diseases Consult
Authors: Guerrero Michelle Grace , Drake Ty , Gentry Clare N , Babic Jessica T 
Published: November 2023

Abstract

Background
Candidemia is associated with high mortality rates in the United States. In 2016, the Infectious Diseases Society of America (IDSA) provided recommendations for the management of candidemia in hospitalized patients. However, there may be further benefit with the addition of an Infectious Diseases consultation (IDC) in patients with candidemia, as seen in patients with Staphylococcus aureus bacteremia.

Methods
We conducted a retrospective cohort study to assess the impact of IDC on adult hospitalized patients with ≥ 1 blood culture positive for Candida species admitted from January 1, 2016 to December 31, 2021. Patients who were deceased or discharged prior to culture positivity, deceased within 24 hours of culture collection, or transitioned to comfort care within 48 hours from the time of positive blood cultures were excluded. The primary outcome was in-hospital and 30-day mortality. Secondary outcomes included duration of candidemia, time to active antifungal therapy, source control, and adherence to IDSA candidemia guideline recommendations.

Results
A total of 195 patients met study inclusion criteria, of which 74.9% had an IDC. In-hospital and 30-day mortality were numerically higher in the non-IDC group, but were not statistically significant (24.7% vs. 34.7%, p=0.17; 18.5% vs 30.6% p=0.07). Duration of candidemia was similar between groups, but trended longer in the non-IDC group (3.25 vs. 3.90 days, p=0.28). Median time to source control, when achieved, was four days in both groups with a higher rate of obtaining source control seen in the IDC group (56.2% vs. 49%, p=0.38). Overall compliance to IDSA guidelines was higher in IDC group versus non-IDC group (47.26% vs. 42.86%, p=0.59).

Conclusion
In our study, IDC was associated with lower in-hospital and 30-day mortality rates in hospitalized patients with candidemia, although not statistically significant. IDC may also be associated with shorter duration of candidemia, higher rate of achieving source control, and higher rates of adherence to the IDSA candidemia guideline recommendations, including using echinocandins as empiric therapy, repeating blood cultures, and conducting eye examinations. A larger study is warranted to solidify the findings of this study.

Disclosures
All Authors: No reported disclosures
824. Combination Antifungal Therapy for Invasive Mucormycosis in Immunocompromised Hosts: A Single-Center Experience
Authors: Lu Brian , Ha David R , Shen Sa , Ferguson Jessica , Kim Ailin , Kim Sarah , Mui Emily , Deresinski Stan , Holubar Marisa , Alegria William 
Published: November 2023

Abstract

Background
Invasive mucormycosis continues to be associated with high rates of mortality despite advances in management strategies. Recent studies have suggested a benefit to early combination therapy, but overall, the data remain limited regarding its impact on outcomes.

Methods
We conducted a retrospective study from January 2009 to December 2022. We included patients aged 18 years or older with proven or probable invasive mucormycosis based on the European Organization for Research and Treatment of Cancer and the Mycoses Study Group 2020 criteria and a history of hematologic malignancy, bone marrow transplant, or solid organ transplant. The primary outcome was all-cause mortality up to 6-weeks after diagnosis. Combination therapy was defined as receipt of &gt;2 Mucor-active antifungals for &gt;3 days and was further categorized as upfront (within 7 days of diagnosis of mucormycosis) or salvage (starting after 7 days post-diagnosis of mucormycosis).

Results
Eighty-two patients met inclusion criteria and were included for analysis. Most patients had a hematologic malignancy (78%) and the most common infection site was pulmonary (62%). Baseline demographics were similar between groups except for the causative organism of invasive mucormycosis. 36 patients (44%) underwent surgical intervention and 58 patients (71%) received combination antifungal therapy. Microbiologically confirmed cases were more common in patients receiving upfront (78%) and salvage combination therapy (50%) compared to monotherapy (34%, p=0.005). Despite being on prophylaxis targeting mucormycosis, 24 patients (29%) developed invasive mucormycosis. After adjusting for surgery, neutropenia, and disseminated disease in multivariate analysis, there was no significant association with either upfront or salvage combination therapy but numerically higher odds of 6-week mortality when compared to monotherapy (OR 1.44, p=0.66 and OR 2.15, p=0.24, respectively).

Conclusion
There was no difference in 6-week mortality for patients receiving antifungal combination or monotherapy for invasive mucormycosis. We observed a numerically higher odds of 6-week mortality in patients receiving combination therapy, which may be explained by confounding by indication.

Disclosures
All Authors: No reported disclosures
827. Adjunct terbinafine in patients with leukemia and invasive fusariosis with skin lesions: Discordance between responses of skin lesions and systemic outcomes
Authors: Matsuo Takahiro , Wurster Sebastian , Jiang Ying , Tarrand Jeffrey , Kontoyiannis Dimitrios P 
Published: November 2023

Abstract

Background
Invasive fusariosis (IF) is a severe opportunistic mold infection with poor outcomes in immunosuppressed leukemia patients (pts). Skin involvement is the second most common manifestation of IF after pneumonia. While in vitro studies have shown synergy of terbinafine (TRB) in combination with triazoles or liposomal amphotericin B (L-AMB) for a variety of fungi, including Fusarium species, clinical data are sparse.

Methods
We retrospectively reviewed adult leukemia pts with proven or probable IF at MD Anderson Cancer Center (Houston, TX) between 2009 and 2021 who received adjunct TRB (aTRB) for skin manifestations of IF, in view of its high bioavailability in skin and skin structures. Demographics, clinical manifestations, antifungal therapy, and outcomes were reviewed.

Results
Among 140 IF pts, we identified 15 pts who received aTRB (dose range: oral 250-1,000 mg/day, duration range: 3-128 days; topical cream in 1 pt) for IF with skin involvement (Table 1). Their median age was 50 (range 21-80); 14 (93%) were male. Eleven pts (73%) had acute myeloid leukemia/myelodysplastic syndrome, 14 (93%) had neutropenia (&lt; 500/µL), and 5 (33%) had a prior hematopoietic stem cell transplant. 13 pts (87%) had disseminated skin lesions, 1 had a localized skin lesion, and 1 had onychomycosis. All 15 patients received antifungal combination therapy. In addition to aTRB, 13 pts received voriconazole + L-AMB, 1 received posaconazole + L-AMB, and 1 received isavuconazole. The median time from IF diagnosis to aTRB initiation was 8 days (range: 0-74). While skin lesions on day 42 after aTRB initiation or at the time of earlier death were improved (6 pts, 40%) or stabilized (4 pts, 27%) in two thirds of patients, the same proportion of pts (10/15, 67%) had progression of IF in sites with poor pharmacologic exposures of TRB (lungs in 7 pts, sinus in 2 pts, endophthalmitis in 1 pt). 10 out of 15 pts died by day 42 (67%) after aTRB initiation.
Patient demographics and treatment outcome
Table 1.

Conclusion
In our limited series, aTRB seemed to display site (skin only)-specific synergistic activity with other systemic antifungals in IF, which is consistent with in vitro synergistic effects and pharmacokinetic aspects of this allylamine which has high skin concentrations. However, TRB use did not affect IF outcomes that were poor in the setting of persistent immunosuppression.

Disclosures
Dimitrios P. Kontoyiannis, MD, MS, ScD, PhD, AbbVie: Board Member|Astellas: Grant/Research Support|Cidara: Board Member|Gilead: Grant/Research Support|Merck: Advisor/Consultant|Scynexis/MSGERC: Board Member
828. Do lung co-infections influence outcome in patients with hematological malignancies and culture-documented invasive pulmonary aspergillosis?
Authors: Matsuo Takahiro , Wurster Sebastian , Jiang Ying , Tarrand Jeffrey , Kontoyiannis Dimitrios P 
Published: November 2023

Abstract

Background
Although pulmonary co-infections are common in patients (pts) with hematological malignancies (HM) and invasive pulmonary aspergillosis (IPA), there is a paucity of recent studies on the type and the impact of co-infections on outcome in contemporary pts with HM and culture-documented IPA.

Methods
We retrospectively reviewed the records of pts with HM at MD Anderson Cancer Center (January 2016 and October 2021) who had microbiologically-documented IPA (based on sputum and bronchoscopy lavage culture) to identify risk factors, clinical features, evidence of co-infections, and outcome. Independent risk factors for 42-day mortality from IPA diagnosis were assessed using a binary multivariable logistic regression model.

Results
Among 128 IPA pts (19 proven, 109 probable), 48 pts (38%) had neutropenia (&lt; 500/µL) and 38 (30%) had prior allogeneic hematopoietic cell transplant. Aspergillus fumigatus was the commonest agent of IPA (41%), Fig. 1). Potential co-pathogens were present in 79 pts (62%) at the time of IPA diagnosis. Bacteria (most commonly Gram-negative rods) and less commonly other fungi were isolated in 32 (25%) and 7 pts (5%), respectively (Fig. 2). In addition, a variety of upper respiratory viruses (40 pts, 31%) and cytomegalovirus (CMV, 15 pts, 12%) were recovered. 42-day mortality after IPA diagnosis was 48%, with no significant difference between pts with and without lung co-infections (48% vs 47%, p &gt;0.99, Table 1). Acute kidney injury (adjusted odds ratio [aOR] 2.51, 95% confidence interval [CI] 1.31-5.17, p=0.003), Sequential Organ Failure Assessment score ≥ 8 (aOR 4.78, 95% CI 2.66-9.41, p=&lt; .0001), and recovery from neutropenia (aOR 0.41, 95% CI 0.20-0.78, p=0.004) were independent predictors of 42-day mortality.
Type of Aspergillus spp (number of isolates)
Figure 1.
Isolated co-pathogens (number of isolates)
Figure 2.
Co-pathogens and 42-day mortality
Table 1.

Conclusion
A quarter of patients with culture-documented IPA had concurrent lung infections with bacteria (especially Gram-negative bacteria) and less commonly with fungi. In addition, co-culture of upper respiratory viruses or CMV was common. In a background of high mortality of culture-documented IPA, there was no excess mortality if a lung co-infection was present. Further studies are needed regarding the impact of inter-kingdom interactions in pts with earlier, galactomannan-based (but BAL culture negative) IPA diagnosis.

Disclosures
Dimitrios P. Kontoyiannis, MD, MS, ScD, PhD, AbbVie: Board Member|Astellas: Grant/Research Support|Cidara: Board Member|Gilead: Grant/Research Support|Merck: Advisor/Consultant|Scynexis/MSGERC: Board Member
833. Interaction between Aspergillus fumigatus and non-tuberculous mycobacteria
Authors: Namie Hotaka , Takazono Takahiro , Koga Satoru , Tashiro Masato , Mukae Hiroshi , Izumikawa Koichi 
Published: November 2023

Abstract

Background
Patients with pulmonary non-tuberculous mycobacteriosis (NTM) have been increasing in Japan in recent years. Furthermore, NTM cases complicated with pulmonary aspergillosis are associated with a poor prognosis. However, little is known about the interaction between Aspergillus spp. and non-tuberculous mycobacterium.

Methods
To investigate the effect of NTM metabolites on A. fumigatus growth and gene expression, supernatants of M. avium (ATCC 700737) and M. abscessus (ATCC 19977) were added to A. fumigatus (Figure 1 and 2).

Results
The biofilms and biomass of A. fumigatus exposed to culture supernatant of each NTM were significantly increased compared to the control (Figure 3). The expression of genes involved in the synthesis of secondary metabolites of A. fumigatus, such as gliotoxin, was decreased after the exposure to supernatant by RNA sequencing analysis (Table 1,2).

Conclusion
Our results suggest that exposure to culture supernatant of NTM may support the growth of A. fumigatus while suppressing the production of some secondary metabolites. We are now trying to reproduce this phenotype in mouse model and to identify the causative agent from NTM culture supernatant and elucidate the mechanism further.

Disclosures
Masato Tashiro, MD, PhD, Asahi Kasei Pharma Corporation: Advisor/Consultant|Asahi Kasei Pharma Corporation: Honoraria|Sumitomo Pharma Co., Ltd.: Honoraria Koichi Izumikawa, M.D., Ph.D., Asahi Kasei Pharma Corporation: Grant/Research Support|Asahi Kasei Pharma Corporation: Honoraria|Astellas Pharma Inc.: Honoraria|DAIICHI SANKYO COMPANY, LIMITED: Grant/Research Support|DAIICHI SANKYO COMPANY, LIMITED: Honoraria|KYORIN Pharmaceutical Co., Ltd.: Honoraria|Merck & Co., Inc.: Honoraria|Pfizer Japan Inc.: Honoraria|Shionogi & Co., Ltd.: Grant/Research Support|Shionogi & Co., Ltd.: Honoraria|Sumitomo Pharma Co., Ltd.: Grant/Research Support|Sumitomo Pharma Co., Ltd.: Honoraria|TAIHO PHARMACEUTICAL CO., LTD.: Grant/Research Support