bluuebunny/crossref_metadata_2025 huggingface dataset:
710. Burden of Clostridioides difficile Infection (CDI) in Flint, Michigan (MI): Association of Race and Gender with Mortality
Authors: Younas Mariam , Amin Hina , Ragheb Elio , Mahgoub Abdullahi , Karki Bibek , Upadhyay Manoj , Bakeer Mohammad , Armor Anthony , Newell Ann , Ríos-Bedoya Carlos F
Published: November 2023

Background

Flint, MI faces an increased vulnerability to health disparities as compared to other communities in MI. Flint & Genesee County’s most critical health needs is informed upon in-part by data provided by the three community hospitals, serving Genesee County, MI, and its urban core, the City of Flint. This cross-sectional study aims to describe our experience with CDI in Flint, MI; and determine 30-day mortality among CDI cases based on gender and race.

Methods

Hurley is a 443-bed premier public teaching hospital (largest in the region). Using National Healthcare Safety Network (NHSN) surveillance Laboratory Identification (Lab ID) events, 926 CDI cases, ≥ 18 years of age were identified among patients hospitalized at Hurley Medical Center from 01/2015 to 07/2022. A positive stool C. difficile test was regarded as a “CDI case” for purpose of this study. NHSN surveillance definitions were used to describe the incident, recurrent cases and determine the epidemiologic categories.

Results

During the 7.6-year study period, 926 cases were identified. 46.7% of the cases were in men, with a 30-day mortality of 10.4% vs 7.3% in women (p-value 0.10) (Table 1). African American (AA) comprised 44.4% of the cases with 30-day mortality of 9.1% vs 8.1% in whites (p-value 0.78) (Table 2). There were 64 recurrent CDI cases with 30-day mortality of 6.3% as compared to 8.9% in incident cases (p-value 0.65). Mean age at specimen collection was 59.9 years (standard deviation (SD) 17.5) with 43% of the cases falling in the age group ≥ 65 years (Table 3). Hospital-onset (HO) and community-onset healthcare facility associated (CO-HCFA) CDI accounted for 42.8% (396/926) and 14.9% (138/926) of the cases respectively. 60.5% (237/392) of the CO CDI were associated with antibiotic use with in the past 90 days as compared to 95.9% (380/396) of HO and 94.9% (131/138) of CO-HCFA CDI (p-value < 0.001).Table 1:CDI cases based on genderTable 2:CDI cases based on raceTable 3:CDI cases based on age groups

Conclusion

CDI caried a significant mortality in this high-risk cohort. Mortality was slightly higher in men and AA; though it was not statistically significant. Antibiotic use was the strongest predictor of CDI acquisition (p-value < 0.001) and about half the CDI cases were CO.

Antimicrobial stewardship initiatives targeting unnecessary and inappropriate antimicrobial use in the community are as imperative as in the hospital setting.

Disclosures

All Authors: No reported disclosures
731. Factors Contributing to Long-Term Risk of Developing Multidrug-Resistant Pseudomonas Recurrence
Authors: Volker Scott , Vogler Andrew J , Fairman Kathleen A , Huang Vanthida
Published: November 2023

Background

Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is a significant healthcare concern in hospitalized patients with a mortality rate upward of 54%. Delayed initiation of appropriate antibiotics with MDR infections may lead to prolonged hospital stays and increased mortality. Previous studies investigated risk factors that contribute to MDR-PA and mortality; however, none evaluated factors leading to recurrence. Therefore, we sought to assess the risk factors contributing to the long-term recurrence of MDR-PA.

Methods

This was a retrospective case-control study of hospitalized patients at HonorHealth Network from January 2015-January 2023. Patients were included if they have ≥2 positive P. aeruginosa cultures in 1-year with MDR as first occurrence. Cases were patients with MDR-PA at second occurrence and controls were patients with no MDR-PA at the second occurrence. MDR-PA was defined as resistance to at least 1 antibiotic in ≥3 different antimicrobial classes. Risk factors associated with a secondary MDR-PA occurrence were evaluated using logistic regression backwards-stepwise analysis of clinical signs and symptoms, demographic, admission location, and number of days since the first MDR-PA occurrence.

Results

Of 8,140 hospitalized patients, 209 (n=132 case, n=77 control) met study entry criteria; 52% were female and 84.8% were Caucasian. Respiratory infections (OR 3.13, 95% CI 1.22-8.04), urinary tract infections (UTIs) (OR 4.51, 95% CI 1.82-11.16), intravenous antibiotic use within the past 30 days (OR 3.03, 95% CI 1.05-8.72), and a time period of 30-59 days since the initial culture positive for MDR-PA (OR 4.34, 95% CI 1.37-13.72) were associated with an increased risk of a secondary occurrence of MDR-PA within 1 year.

Conclusion

Our study revealed that there is an increased risk of subsequent recurrence between 30-59 days following the initial MDR-PA positive culture. However, further investigations are warranted in the future to be generalizable.

Disclosures

All Authors: No reported disclosures
743. Efficacy and persistence of 3M™ Skin and Nasal Antiseptic for reduction of S. aureus colonization ex vivo porcine tissue model
Authors: Laubach Isabel A , Peterson Marnie L , Parthasarathy Ranjani
Published: November 2023

Background

Surgical-site infections can result from nasal colonization of Staphylococcus aureus prior to surgery. Nasal decolonization with iodine-based products is a common way to combat this problem. The efficacy and persistence of nasal decolonization products is a crucial component for this presurgical protocol to be successful. An ex vivo porcine mucosal model allows for clinically relevant testing of formulations without the need for live animals.

Methods

Fresh porcine vaginal mucosa was processed to create 5 mm diameter explants. One group was left uninfected, and the other was infected with prepared methicillin-resistant S. aureus (MRSA) Xen30 to achieve 106 CFU/explant and incubated for 2h at 37 °C. After 2-hour incubation, explants were treated with formulation for 1h then gently washed with mucin and incubated for 24h at 37 °C. Uninfected explants were photographed prior to treatment, immediately post treatment, pre and post wash, and at hour intervals following mucin wash. Infected explants were collected into neutralizing solution at 24h, vortexed and sonicated to liberate bacteria then plated to enumerate CFU/explant. Additional infected explants were stained with LIVE/DEAD stain and imaged by fluorescence microscopy at 24h.

Results

Pictures of uninfected, treated explants showed that 3M™ Skin and Nasal Antiseptic (SNA) formulation persisted visually on the tissue up to 6h post wash while Betadine was no longer visible on tissue at 1h post wash. At 24h post wash, explants treated with Skin and Nasal had no recoverable colony forming units while explants treated with Betadine had regrown to ∼7 Log10 CFU/explant. This finding was confirmed by staining and fluorescent imaging. Fluorescent imaging showed that treatment of uninfected explants with SNA or Betadine did not compromise tissue viability compared to untreated control; however, infected explants treated with Skin and Nasal retained the most tissue viability.

Fluorescent images of porcine vaginal mucosa stained with LIVE/DEAD stain following 24h incubation with formulations.

Conclusion

The material properties of SNA prep allow it to remain on the tissue even after washing resulting in longer lasting activity against MRSA Xen30 than Betadine treatment over 24 hours. By persisting, the SNA treated explants showed reduced tissue damage by MRSA than was observed in the Betadine and untreated groups.

Disclosures

Ranjani Parthasarathy, PhD, 3M: Have patents|3M: 3M employee|3M: Stocks/Bonds
751. The success of an escape room activity on antimicrobial stewardship in achieving Doctor of Pharmacy Educational outcomes
Authors: Lee Yuman , Bradley Nicole
Published: November 2023

Background

ASP Escape Room was an activity created and conducted in the infectious disease elective for pharmacy students in their 3rd professional year. Students were assigned the CDC Core Elements of ASP as a pre-reading. During class, students worked in groups of 4 on tasks relating to the CDC Core Elements to decode various puzzles to advance through the activity in establishing an antimicrobial stewardship program. The goal of ASP Escape Room was to engage and motivate students to learn foundational antimicrobial stewardship concepts and challenge students to develop personally and professionally. The purpose of this study was to assess the impact of ASP Escape Room on achieving Doctor of Pharmacy Curriculum Outcomes and Entrustable Professional Activities (COEPA) 2022 and evaluate perceptions.

Methods

During the Spring 2023 semester, student feedback was anonymously collected via an electronic survey. Students evaluated the impact of ASP Escape Room based on the 3 domains of COEPA 2022 (Knowledge, Skills, and Attitudes) on a Likert scale from strongly disagree to strongly agree. 

Results

39 students responded. Majority strongly agreed or agreed that ASP Escape Room allowed them to learn foundational knowledge (38/39, 97.4%), develop problem solving skills (37/39, 94.9%), improve effective communication skills (38/39, 97.4%), understand the role of a steward in optimizing healthcare (39/39, 100%), achieve shared goals on a team (38/39, 97.4%), and build/maintain trust among colleagues (39/39, 100%). Additionally, students enjoyed participating (38/39, 97.4%), reported the activity was an engaging way of learning antimicrobial stewardship (38/39, 97.4%), and that they would like to participate in future escape room activities as part of pharmacy course work (36/39, 92.3%). Most students ranked the activity’s difficulty as a 3 (61.5%) or 4 (30.8%) out of 5.

Conclusion

ASP Escape Room was positively received and provided an opportunity for students to expand beyond foundational knowledge, and develop on the and skills and attitudes domains, including building trust, effective communication, and supporting team goals. Opportunities like ASP Escape Room Activity are important in the education of pharmacy students to prepare them to practice at the highest level of the profession.

Disclosures

All Authors: No reported disclosures
757. Bridging the Gap: An Educational Intervention to Increase HIV PrEP Access in Resident Primary Care Clinics
Authors: Davis Jennifer M , Solomon Daniel A , Alexander Erik K , Ramani Subha
Published: November 2023

Background

HIV Pre-Exposure Prophylaxis (PrEP) is a safe and effective way to prevent HIV acquisition. Yet, in 2020, only 25% of individuals in the US and Puerto Rico who had an indication for PrEP received a PrEP prescription. While PrEP is accessible to primary care clinicians, many do not feel comfortable prescribing PrEP. Clinician education has been identified as a key opportunity to increase access and comfort in prescribing PrEP.

Methods

An educational intervention was designed aiming to increase PrEP knowledge and prescribing among residents and preceptors in the primary care clinics at Brigham and Women’s Hospital (BWH). The intervention followed the six steps described in Kern’s model of curriculum development (Figure 1). After formal needs assessment, an in-person interactive teaching session was designed and presented. This was supplemented by an online reference guide and note template dot phrases accessible in the electronic medical record (EMR). The curriculum was evaluated with pre and post intervention surveys. Survey data were analyzed using descriptive statistics and one tailed T tests.

Results

Of the approximately 30 residents and preceptors who participated in the intervention, 19 completed the pre survey and 9 completed the post survey. Only 37% (7/19) of pre survey respondents reported having had PrEP education in the past. 21% (4/19) had prior teaching during medical school, 21% (4/19) during residency, and 16% (3/19) in continuing medical education courses. Participants indicated that their comfort with prescribing PrEP increased overall after the intervention with a statistically significant increase in reported confidence in their ability to prescribe PrEP (mean Likert scale value of 3.88 vs 2.95, p = 0.03) (table 1).

Conclusion

PrEP is an underutilized modality in preventing HIV transmission, but many primary care clinicians do not feel comfortable prescribing PrEP even though it is accessible in primary care settings. Systematic PrEP education is lacking in the UME, GME, and CME settings. Targeted, interactive, multimodal educational interventions can be effective in increasing comfort with PrEP prescribing. Support from leadership and learner buy-in is critical for effective training.

Disclosures

All Authors: No reported disclosures
760. Multidisciplinary Education in Substance Use Disorder Centers Improves HIV Prevention Knowledge and Practice: BRIDGE PrEP: Building Bridges to Reach People Who Inject Drugs with the Goal of Employing PrEP for HIV Prevention
Authors: Glazar Amanda , Carney Becky K , Simpson Mara S , Daniels Susan , Felzien Gregory S
Published: November 2023

Background

Around 10% of new HIV infections in the US are attributed to injection drug use or male-to-male contact and injected drug use; syringe sharing is the second riskiest behavior for contracting HIV. For many, substance use disorder (SUD) treatment is the primary point of access for receiving HIV-related services. A 2021 survey showed gaps in HIV prevention knowledge and practice among SUD center staff but also interest in education (Fig 1). The BRIDGE PrEP program is a grassroots initiative designed to educate and motivate SUD center staff to increase their clients’ awareness of and access to HIV preexposure prophylaxis (PrEP) services.

Methods

Ten live continuing medical education (CME) meetings supported by an educational grant from Gilead Sciences, Inc were conducted at SUD centers between August 2022 and May 2023. The 1-hour meetings provided didactic information, real-world insights, faculty-learner interactions, local networking, and take-away print and online staff/patient-education resources (Fig 2). Program goals include:1.Increase HIV testing of people who inject drugs 2. Educate SUD center staff regarding PrEP harm-reduction practices and 3.Build linkages between SUD staff, PrEP providers, and HIV-care networks within local/regional systems. Moore’s Level 1-5 (self-reported) outcomes (Fig 3) were collected via pre-, post-, and 6-week follow-up surveys evaluating knowledge and self-reported frequencies of recommended HIV prevention practice behaviors.

Results

To date, there have been 154 participants representing a diverse multidisciplinary learner group extending beyond the clinician-only audience typical of many CME programs (Fig 4). Increases in knowledge were demonstrated across topic areas (Fig 5), and participants reported intent to improve HIV prevention-related practices following the activity (Fig 6). To date, follow-up surveys report specific actions taken on individual and system levels to improve HIV screening and prevention (Fig 7).

Conclusion

Positive outcomes related to HIV prevention knowledge and practice among SUD center staff have the potential to impact many at-risk individuals. Additionally, follow-up surveys suggest that improved awareness is prompting collaboration and system-level changes driven by participants (Fig 8).

Disclosures

All Authors: No reported disclosures
763. Infection Prevention Resource Physicians to Build On-Call Capacity
Authors: Hayes Ericka , Smathers Sarah , Townsend Sara , Le Goff Lauren , Plaras Marisse , John Audrey , Fatemi Yasaman , Sammons Julia
Published: November 2023

Background

The COVID-19 pandemic showed that infection prevention and control (IPC) human resources are critical and are stretched in prolonged crisis. There has also been a shift from experienced infection preventionists (IPs) during the pandemic and natural attrition to a less experienced cohort. Medical Director (MD) oversight of IPC programs is critical in providing clinical guidance and support for developing IPs. IPC and MD resources are required 24/7 to respond to urgent issues such as management of highly infectious exposures. Many IPC programs have a single MD with extensive on call periods stretching a limited resource and increasing potential for physician burnout. We report the impact of Infectious Diseases Resource Physicians (IDRP) to support IPC on call.

Methods

Our large pediatric health system had a gap in MD coverage from June 2022-October 2022. To support IPC on call, we developed a weekly rotating IDRP staffed by an inpatient ID physician with MD backup as needed. After a senior MD onboarded in October 2022, the IDRP rotation was expanded to other ID physicians on a voluntary basis. Education in management of common urgent/emergent IPC issues was provided to all IDRPs. Data was collected on time spent and themes by IDRPs.

Results

From October 2022-April 2023 we have had 11 IDRPs provide IPC support. Calls per week ranged from 0-5 with a median of 1. Time investment by IDRP weekly was a median of 10 minutes, range 0-60 minutes, spent supporting IPC questions. Common themes were communicable diseases such as tuberculosis, assessing symptomatic caregivers/parents and type of precautions needed. Feedback from the IPC team and IDRPs was positive as solicited through meetings, emails and individual inquiry.

Conclusion

We have successfully established ID physician support coverage for our IPs on call, building a bench of IPC expertise throughout our ID group and supporting the single senior MD. Additional capacity for the IPC program provides flexibility and support needed during critical times, such as pandemic response. IPs felt well supported by the IDRP with the additional benefit of strengthening relationships across the IPC team and ID division. Key factors in success include clear expectations, education, feedback, and support.

Disclosures

All Authors: No reported disclosures
773. The Role of Infectious Diseases Physicians in Postgraduate Antimicrobial Stewardship Education: A Nationwide Questionnaire Survey in Japan
Authors: Miwa Toshiki , Okamoto Koh , Okamoto Koh , Nishizaki Yuji , Tokuda Yasuharu
Published: November 2023

Background

To promote appropriate antimicrobial use, resident physicians’ understanding of antimicrobial stewardship (AS) is essential. While infectious disease (ID) physicians are expected to play a leading role in AS education, data are limited for the impact of ID physicians’ involvement. We aimed to evaluate the impact of direct interaction with ID physicians on resident physicians’ knowledge, perceptions, and attitudes regarding AS.

Methods

A cross sectional study involving the participants of the Japanese nationwide online examination for resident physicians in January 2023 was performed. The questionnaire with 29 items on their educational background as well as perceptions and attitudes regarding AS were distributed, collected, and analyzed in combination with the examination scores.

Results

Of 8,438 post-graduate year (PGY) 1 and 2 resident physicians participated in the examination, 4,051 (48.0%) from 577 institutions responded in the present study. A half (54.0%) worked at hospitals with an existing ID department (Table 1). A third (32.7%) did not receive any formal AS education during their residency program whereas 65.2% failed to understand the concept of AS, and 79.2% were less confident in choosing appropriate antimicrobials. Among respondents working at hospitals with an ID department, presence of bedside ID consultation service was associated with enhanced commitment to choosing narrow-spectrum antimicrobials, de-escalation, transition to oral therapy, and compliance of appropriate duration of therapy than ID consultation only based on chart review (49.6% vs. 42.6%, 51.4% vs. 41.6%, 76.3% vs. 66.3%, 66.7% vs. 55.7%, respectively [all of P < 0.05]) (Table 2). Although there was no statistically significant difference in total test scores, respondents who had an ID rotation were more likely to review past antimicrobial exposure and colonization of resistant pathogens and try to choose narrow-spectrum antimicrobials than those who received lectures only (59.3% vs 39.0%, P < 0.001) (Figure).

Conclusion

Resident physicians’ perceptions and attitudes regarding AS may improve through direct interaction with ID physicians. Our findings underscore the imperative role and value of ID physicians as key educators for future physicians.

Disclosures

All Authors: No reported disclosures
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

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< 0.00). Average quiz scores improved on all topics (p< 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

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< 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< 0.05). In multivariable linear regression analysis, factors associated with higher knowledge scores included higher academic year (P< 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

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

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

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

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 >2 Mucor-active antifungals for >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

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 (< 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

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 (< 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 >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=< .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

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
846. Pneumocystis Pneumonia in malignancy patients: Who is at risk?
Authors: Vasiloudes Kritos , Aslam Sadaf , Greene John
Published: November 2023

Background

Pneumocystis Pneumonia (PCP) is a respiratory pathogen that has been known to cause severe illness in the immunocompromised patients. The pathogen became well known in the HIV epidemic where much of the current standard of practice was first researched. However since the invention of antiretroviral therapy, and advances in cancer therapy the population affected by PCP has shifted to patients with malignancy or a medication induced immunocompromised state. Here we wish to better define the epidemiology and pathogenicity of PCP in the immunocompromised malignancy patients.

Methods

We utilized a retrospective review of 28 consecutive patients from January 1st 2012 to January 1st 2023 that had visited Moffitt Cancer Center with a diagnosis of confirmed or suspected PCP. We collected data on age, underlying malignancy, type of treatment, comorbidities, presenting symptoms, method of diagnosis and computed tomography findings.

Results

Hematologic malignancies comprised 90% of all cases, half of all cases were in patients’ with a type of non-hodgkin’s lymphoma (NHL). The most common malignancy was diffuse large B cell lymphoma 25%, followed by acute myelocytic leukemia treated with stem cell transplant (SCT) 14%, followed by multiple myeloma 11% (Figure 1). The therapy mostly implicated was glucocorticoids in 57% cases, followed by alkylating agents in 32%, and SCT in 25% (Figure 2). The most frequently reported symptoms was dyspnea in 71% of patients, followed by fever 39%, and cough 32%. Diagnosis was made in 21% of patients with serum 1,3-β -D-glucan, 68% were diagnosed following a bronchoalveolar lavage, 11% utilized both (figure 3). of The most common finding on CT was ground glass opacities in 79% of cases. Lymphopenia was present in 79% cases. PCP contributed or was the cause death in 17% cases.

Underlying Malignancy

Underlying Malignancy of those who developed PCP pneumonia, n=28 Diffuse large B Cell Lymphoma DLBCL, Acute Myelocytic Leukemia AML, Chronic Lymphocytic Leukemia CLL, Cutaneous T Cell Lymphoma CTCL, Acute T cell Leukemia/Lymphoma ATLL, Immune Thrombocytopenic Purpura (ITP)

Type of cancer treatment

Cancer Treatment of those who developed PCP pneumonia, multiple different therapies were often used in treatment, n=28

Method of Diagnosis of PCP

Conclusion

Our data shows that patients’ with NHL comprise half of the patients who developed PCP. Consistent with other studies, steroids were the most frequently implicated therapy, however the second most frequent were alkylating agents. Lymphopenia was commonly associated as well. We wish to bring to light that NHL, Alkylating agents, and particularly lymphopenia as risk factors for development of PCP and should prompt early concern of PCP, particularly those with NHL.

Disclosures

All Authors: No reported disclosures
848. Discordant Chest Radiography and Computed Tomography Findings in Patients with Hematologic Malignancy and Invasive Mucormycosis: What Are the Prognostic Implications?
Authors: Wurster Sebastian , Franklin Alexander D , Axell-House Dierdre B , Jiang Ying , Kontoyiannis Dimitrios P
Published: November 2023

Background

Invasive pulmonary mucormycosis (IPM) is a common and deadly mold infection in patients (pts) with hematological malignancies (HM). Comparing chest x-ray (CXR) to computed tomography (CT) in IPM offers the opportunity to evaluate the concordance of these two imaging studies and the clinical significance of discordant imaging.

Methods

We reviewed all HM pts with CT-positive probable/proven IPM at MD Anderson Cancer Center (2000-2020) who had a concurrent CXR performed within 5 days of the reference CT. Concordant imaging was defined as a consolidation or mass-like lesion on CXR matching the suspicious CT lesion. In addition to survival curve analysis, a multivariate Cox's proportional hazard model was used to identify independent predictors of 84-day all-cause mortality after IPM symptom onset.

Results

Among 44 included pts, 31 (70%) were neutropenic (< 500/µL). Only 24 pts (55%) had a matching lesion on CXR while the remaining 20 (45%) had discordant imaging. 20/29 pts (69%) with consolidation on CT and 9/12 pts (75%) with reverse halo sign or nodules with cavitary lesions had concordant CXR findings, whereas nodules without these features were rarely associated with concordant CXR findings (7/26, 27%). Although infection severity at baseline (APACHE II scores 15 vs. 16) was comparable, pts with concordant CXR lesions tended to have higher rates of intensive care unit admission during IPM therapy (67% vs. 45%, p = 0.15) and higher 84-day mortality (92% vs. 65%, p = 0.06) than those with discordant imaging. This difference was corroborated by survival curve analysis (Fig. 1A, p = 0.008), even when restricted to the 31 neutropenic pts (Fig. 1B, p = 0.049). APACHE II score > 18 at IPM diagnosis (adjusted hazard ratio [aHR] 3.09, p = 0.003), neutrophil recovery (aHR 0.29, p = 0.007), and presence of a concordant CXR lesion (aHR 2.61, p = 0.011) were independent predictors of 84-day mortality (Table 1).

Figure 1

Table 1

Conclusion

Even when accounting for neutropenia status, a known confounder of radiographic imaging in IPM pts, visualization of IPM on CXR concordant to CT was an independent predictor of poor outcomes, possibly as a surrogate of extensive lesions and high fungal burden. If confirmed in larger cohorts, CXR might be used as a supportive prognostic staging tool in IPM pts, especially in resource-poor settings.

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