bluuebunny/crossref_metadata_2025 huggingface dataset:
339. OPAT Outcomes in Patients with Immunocompromise
Authors: Mahoney Monica V , Swords Kyleen , Le Mahajan Audrey , Alonso Carolyn D , Larnard Jeffrey
Published: November 2023

Background

Outpatient parenteral antimicrobial therapy (OPAT) allows patients to complete intravenous (IV) or high risk oral medications outside the acute inpatient setting. Data regarding OPAT in patients with immunocompromise (PWIC) are sparse. PWIC represent a vulnerable population due to underlying comorbidities. This study evaluated OPAT clinical outcomes in PWIC at an academic medical center.

Methods

This was a retrospective chart review of adult PWIC enrolled in our OPAT program between 1/2015-3/2023. Immunocompromising conditions included HIV/AIDS, stem cell or solid organ transplant, hematologic malignancy, solid tumor, or receipt of immunosuppressing medications. All patients were under the care of an immunocompromised ID specialist. Data collected included patient demographics, infection information, and OPAT outcomes including completion rates, readmission rates, OPAT failure, and death. OPAT failure was defined as death, 30-day infection-related readmission or 30-day OPAT-related complication. This study was exempt by the Institutional Review Board.

Results

50 patients were included. Demographics are in Table 1. Most (68%) patients completed OPAT therapy in the home, with 82% of courses being IV-only. Most (72%) patients received 1 antimicrobial agent, but 20% received 2 and 8% received 3 agents. The most common agents were daptomycin, ertapenem, and vancomycin.

Infection information is in Table 2. Bloodstream infections and osteomyelitis were the most common. Most (82%) patients had an organism identified: 51% were Gram positive, with Staphylococci the most prevalent. Cytomegalovirus was the reason for OPAT in 4 patients.

OPAT outcomes are in Table 3. OPAT failure occurred in 9 patients, including 1 death and 8 OPAT-related readmissions. Most (68%) patients completed the OPAT course within the specified time. Hospital readmissions were common: 46% had at least 1 readmission, though most readmissions were unrelated to OPAT. Vascular device issues and adverse drug reactions occurred in 12% and 20%, respectively.

Conclusion

OPAT can be safely performed in PWIC with completion and complication rates comparable to non-immunocompromised cohorts. We observed high hospital readmission rates (46%) though a minority of readmissions were due to OPAT related issues.

Disclosures

Monica V. Mahoney, PharmD, BCPS, BCIDP, FCCP, FIDSA, FIDP, BD Biosciences: Advisor/Consultant|Cidara Therapeutics: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Grant/Research Support|Open Forum Infectious Diseases: Board Member|Open Forum Infectious Diseases: Associate Editor|Pfizer: Advisor/Consultant Carolyn D. Alonso, MD, Academy for Continued Healthcare Learning: Honoraria|AiCuris: Advisor/Consultant|American Society of Healthcare Pharmacists: Honoraria|Cidara Therapeutics: Advisor/Consultant|Clinical Care Options: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support
340. Infections in The Unhoused: A Descriptive Review of Unhoused People Presenting to The Emergency Room with Fever
Authors: McFarland Jessica M , Rawal Ruchi , Yan Yueqi , Sivasubramanian Geetha
Published: November 2023

Background

Homelessness has been increasing in several cities in California. The US Department of Housing and Urban Development and the Fresno Madera Point in Time Homeless Count, estimates that 4,216 people were experiencing homelessness during the year 2022 alone in Fresno County (Fig 1). People who are homeless often lack adequate health insurance, access to medical care, and have low healthcare literacy. They are subjected to poor sanitation and overcrowded living conditions putting them at risk for communicable diseases. Comprehensive studies of febrile illnesses in unhoused patients are sparse. We retrospectively studied unhoused individuals who presented to our center with fever. We aimed to quantify and understand their underlying presenting infections.

Areas shown in red represent increase in homeless counts between 2019 and 2020

Methods

The Fresno Information Gateway (FIG) is an IRB (Institutional Review Board) approved database which has data captured on patients seen in our center. We used ICD 10 codes for unhoused, fever and subset of infections to obtain data between 2015-2019 (Fig 2). Crosstabulation and chi-square or Fisher’s exact test were performed to examine the frequency and percentage of individuals with each type of disease. T-test was used to compare the average age between samples with vs. without each disease. Logistic regression was performed to examine the association of factors with each disease, while controlling for other factors.

Results

A total of 4792 unhoused patients were seen in the study period. Of these, 2177 patients presented with a fever (Table 1). Unhoused females had higher odds of presenting with blood stream and urinary tract infections (Table 2). Substance abusers had higher odds of soft tissue, cardiac and respiratory infections. Unhoused Asians or Pacific Islanders had higher odds of coccidioidomycosis, compared with their White counterparts.

Conclusion

A large number of unhoused patients presented to our center in Central California with febrile illness due to various infections. Unhoused females, substance users and HIV positive individuals in our study-set had higher odds of presenting with certain infections. Further studies are warranted to examine these associations, which may help us develop disease specific healthcare delivery models in unhoused patients.

Disclosures

All Authors: No reported disclosures
351. Factors Predicting Readmission within 90 days in Patients Receiving Outpatient Parenteral Antibiotic Therapy
Authors: Smola Kyle , Silliman Julia , Ho Minh , Mercurio Amanda
Published: November 2023

Background

Outpatient Parenteral Antibiotic Therapy (OPAT) involves administering antibiotics outside hospitals via non-oral routes. Success depends on well-reasoned selection of patients for this treatment modality and proper antibiotic stewardship to avoid serious complications.

Methods

We created a de-identified dataset (n=295) from a retrospective chart review of veterans receiving OPAT at the Orlando VA Medical Center (ORL-VAMC) in 2020. We included patients aged 18 or older who underwent OPAT therapy at ORL-VAMC with at least one antibiotic administration between January 1 and December 31, 2020. Inclusion also required compliance with follow-up and laboratory monitoring for at least 90 days after starting outpatient antibiotics. Of 364 patients receiving OPAT during 2020, 295 met the full criteria, with loss to follow-up and absent labs as common reasons for exclusion. We examined patient demographics, medical history, diagnosis, and elements of treatment for associations with unplanned hospital visits within 90-days of OPAT initiation using Binary Logistic Regression modeling.

Results

The average age within the dataset was 67.37 (SD=±11.38) years. Common treatment indications included Osteomyelitis (80/295, 27.12%) and Bacteremia (64/295, 21.69%). 40.96% (119/295) of patients had an unplanned hospital visit within 90 days, primarily due to unresolved symptoms. Our regression model identified Pyelonephritis/UTI (OR 2.26; 95% CI 1.02-5.41), Intra-Abdominal Infection (OR 3.81, 95% CI 1.15-17.45), Cephalosporin Antibiotics (OR 2.57, 1.39-4.91), Liver Disease (OR 2.26, 95% CI 1.02-5.41), and psychiatric illness (OR 1.74, 95% CI 1.06-2.87) as being significantly associated with unplanned hospital visits within 90 days.

Conclusion

A majority (177/295, 60%) of patients did not need further care in the hospital setting after starting OPAT. Our study supports OPAT as an effective option for delivering IV antibiotic therapy when indicated. This study's external validity is limited by the overrepresentation of males in the sample. Nevertheless, these findings can help physicians better anticipate successful outcomes and select suitable patients for OPAT. Further research aimed at understanding the associations identified may offer improved clinical utility.

Disclosures

All Authors: No reported disclosures
357. High Rate of Adverse Events in Patients Receiving Oral Antimicrobials Under a COpAT Monitoring Protocol
Authors: Sawey Ciara , Burgoyne Colleen , Winbush Angelina , Temple Craig , Qualls Brandon W , Munsiff Sonal , Yamshchikov Alexandra
Published: November 2023

Background

Oral linezolid (LZD), trimethoprim sulfamethoxazole (SXT), voriconazole (VRC), and itraconazole (ITC) are used often for prolonged durations and are associated with an array of adverse events (AEs). Establishing specific protocols for monitoring such courses of Complex Outpatient Antibiotic Therapy (COpAT) regimens as parenteral alternatives is a priority.

Methods

Patients receiving LZD, SXT, VRC, ITC between January 1st, 2019 and December 31st, 2022 with monitoring by our Outpatient Parenteral Antimicrobial Therapy (OPAT) program staff were identified for retrospective review of electronic health records. Weekly labs were highly encouraged in the first month of therapy, and at least monthly thereafter. All patients were reviewed during weekly OPAT rounds. An AE grading tool was derived using Common Terminology Criteria for Adverse Events (CTCAE 2017) to capture common AEs associated with study drugs. Primary study endpoint was occurrence of up to three AEs of any severity during antibiotic therapy. Secondary analyses evaluated risk factors and treatment outcomes associated with AE occurrence using chi-square statistic (MedCalc Software Ltd.).

Results

A total of 133 adverse events were identified in 70 (56.5%) of 124 patients receiving COpAT with LZD, SXT, VRC, ITC. Most common infections were pulmonary, bone/joint, and bacteremia/endocarditis (Figure 1). Median length of therapy ranged 21 days (LZD) to 102 days (ITC). Median time to AE onset ranged 8 days (SXT) to 14 days (VRC). Most AEs (88.3%) were < Grade 2 in severity, but 44 (62.9%) of 70 patients incurred > 2 AEs per treatment course. Although VRC incurred highest proportion of AEs, rates were > 50% for all agents (Figure 2), and gastrointestinal AEs were most common (Figure 3). Occurrence of AE of any severity was significantly associated with modification of drug regimen and change in treatment duration.Figure 1.Infectious Disease Diagnoses Represented Under COpAT. Pulmonary, bone/joint, and endovascular infectious were most commonly represented.Figure 2.Proportion of Study Patients with Adverse Events by Medication. Adverse events were incurred in half or more of all treatment courses represented in this studyFigure 3.Adverse Event Categories by Medication.

Gastrointestinal toxicity was most frequently represented, followed by derangements in electrolyte or renal function.

Conclusion

High rates of multiple low- grade AEs per patient treated were associated with use of oral LZD, SXT, VRC, and ITC for severe infections, and frequently required modifications in regimen or duration of therapy. Evidence based protocols are needed to help guide monitoring and clinical management for patients receiving COpAT with these important agents.

Disclosures

All Authors: No reported disclosures
358. Differences in antibiotic usage patterns in Korean hospitals according to the appropriateness of surgical prophylactic antibiotic use: a Nationwide study
Authors: Yoon Choseok , Shin Jihye , Kim Dong-Sook , Chae Jungmi , Yoon Sang-Heon , Kim Yeseul , Jang wooyoung , Kim Jinnam , Kim Bongyoung
Published: November 2023

Background

Since 2007, the Health Insurance Review and Assessment Service (HIRA) has been conducting an appropriateness evaluation of prophylactic surgical antibiotic use for all hospitals in Korea. Each of the hospitals were divided into 5 grades based on their evaluation results. The purpose of this study is to analyze the differences in antibiotic usage patterns in Korean hospitals based on the appropriateness of surgical prophylactic antibiotic use.

Methods

We analyzed all antibiotics prescribed from hospitals included in the 9th appropriateness evaluation of surgical prophylactic antibiotic use from January 2020 to December 2021, using National Health Insurance claims data submitted to the HIRA. Antibiotic usage was calculated as Days of Therapy (DOT) and then adjusted to 1,000 patient-days. We compared antibiotic usage patterns with a surgical prophylactic antibiotic usage evaluation grade 1 or 2 hospitals and those with other grades hospitals. In addition, we analyzed the factors associated with grade 1 using logistic regression analysis.

Results

Among a total of 338 hospitals, 198 (58.6%) of hospitals received grade 1 or 2. The total antibiotic usage (253.4 vs. 169.6, P < 0.001) and the usage of antibiotics predominantly used for resistant gram-positive bacteria (11.0 vs. 8.2, P < 0.001) were higher in grade 1-2 hospitals than in other hospitals, while the usage of broad-spectrum antibiotics mainly used for hospital-onset infections (32.1 vs. 40.3, P=0.043) and Narrow-spectrum beta-lactam antibiotics (135.8 vs. 165.4, P=0.002) were lower in grade 1-2 hospitals than in other hospitals. Logistic regression analysis showed that factors associated with grade 1 were the Charlson's comorbidity index of patients (OR 3.59, 95% CI 1.61-8.03), the proportion of cancer patients (OR 0.98, 95% CI 0.98-0.99), and the number of infectious disease specialists (OR 1.10, 95% CI 1.07-1.14).

Conclusion

The overall use of antibiotics and the use of antibiotics mainly used for resistant gram-positive bacteria were higher in grade 1-2 hospitals than in other hospitals; the use of broad-spectrum antibiotics commonly used for hospital-acquired infections and narrow-spectrum beta-lactam antibiotics were lower in grade 1-2 hospitals than in other hospitals.

Disclosures

All Authors: No reported disclosures
363. A Phase II Prospective Randomized Study to Assess Imipenem-Relebactam in the Management of Cancer Patients with Febrile Neutropenia
Authors: Chaftari Anne-Marie , Dagher Hiba , Hachem Ray Y , Jiang Ying , Lamie Peter , Dib Rita Wilson , John Teny , Haddad Andrea , Philip Ann , Ali Shahnoor , Mulanovich Patricia , Juan Ying , Chaftari Patrick , Raad Issam I
Published: November 2023

Background

The overuse of antibiotics has led to the emergence of antibiotic resistance that poses a significant threat particularly for the immunocompromised cancer patients. Hence, the empiric therapy with standard antibiotic could be suboptimal in these vulnerable patients who often receive antibiotic treatment. New antibiotics that cover potential resistant pathogens may be considered.

In this prospective study we wanted to evaluate the role of a new combination of β-lactam/β-lactamase inhibitor Imipenem-Relebactam (IR) in comparison to standard of care (SOC) antibiotics in the empiric treatment of cancer patient with febrile neutropenia.

Methods

We conducted a prospective, randomized, open-label study comparing the safety and efficacy of IR vs SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) used in combination with gram-positive antibacterial agents as empiric therapy in adult cancer patients with febrile neutropenia. Patients received at least 48 hours of intravenous (IV) antibiotics before any switch of antibiotic was allowed and were followed through end of intravenous (EOIV) therapy and for up to 42 days.

Results

A total of 80 patients were enrolled between October 2021 and April 2023 of whom 39 were randomized to IR and 41 to SOC. Age, gender, race, and underlying malignancies were similar in both groups. The rate of microbiological infection including bacteremia was similar in both groups (27% in IR vs. 31% in SOC; p=0.81). Favorable clinical response at EOIV was comparable in both groups (88% in IR vs. 72% in SOC; p=0.12). The microbiological eradication at EOIV was 100% in IR vs 75% in SOC; p=0.22. Study-drug related adverse events were similar in both groups (10% in IR vs. 18% in SOC; p=0.29). Although overall mortality at late follow up was higher in SOC arm (11% in SOC vs. 0 in IR; p=0.049), there was no study-drug related mortality.

Conclusion

The use of IR as empiric coverage of febrile neutropenia in cancer patient is efficacious and safe and could be associated with a lower overall mortality.

Disclosures

Issam I. Raad, Distinguished Professor, Novel Anti-Infective Technologies, LLC: Technology License
384. Factors Potentiating the Risk of Linezolid-induced Thrombocytopenia in Patients without Haemato-oncologic Diseases: A Case-control Study
Authors: Thabit Abrar K , Alghamdi Arwa A , Alsaeed Afnan K , Magbool Nesreen M , Mahrous Ahmad J , Alrowaili Alya , Alsowaida Yazed S , Albakistani Ziyad K , Albangali Basem O , Alghumuy Anas M , Youssef Sara A , Alodayli Reem M
Published: November 2023

Background

Thrombocytopenia is a major adverse effect of linezolid due to myelosuppression. Many studies assessed factors associated with this effect, but most included patients with haemato-oncologic diseases, which may confound the assessment of thrombocytopenia. Therefore, this study aimed to investigate risk factors for linezolid-induced thrombocytopenia in patients without haemato-oncologic diseases.

Methods

This was a multicenter retrospective case-control study of adults treated with linezolid 600 mg twice daily for ≥ 3 days. Cases were the patients who developed thrombocytopenia while controls are those who didn't develop it. Exclusion criteria were haemato-oncologic diseases, active COVID-19, active dengue fever, baseline platelet count < 100 × 103/mm3, concurrent therapy with trimethoprim/sulfamethoxazole or valproic acid, platelet transfusion within 7 days before linezolid therapy, and insufficient platelets data. Various factors were assessed for potential association with linezolid-induced thrombocytopenia (defined as drop in platelet count below 100 × 103/mm3).

Results

142 patients were included, 31 cases and 111 controls. Patients in both groups had a median age of 62 years and received linezolid for a median of 8 days. Platelet counts significantly dropped in the cases (Figure 1). Figure 2 shows the trend of change in platelet count (the white square indicates the median duration to thrombocytopenia, 8 days). In the univariate analysis, serum creatinine, creatinine clearance, baseline hemoglobin, baseline platelet count, and bacteremia were significantly associated with thrombocytopenia. However, after adjusting for confounders in the multivariate analysis, only low baseline hemoglobin and bacteremia were associated with thrombocytopenia (adjOR = 0.71; 95% CI 0.53-0.95; P = 0.022 and adjOR = 17.02; 95% CI 1.15-251-71; P = 0.039, respectively). Among the cases, those who had a baseline platelet count of < 200 × 103/mm3 developed thrombocytopenia faster as early as 3 days (log-rank P = 0.002; figure 3).

Figure 1

Rate of change in platelet count between the cases (thrombocytopenia) and controls (no thrombocytopenia)

Figure 2

Trend of platelet counts over 14 days in the cases (thrombocytopenia) and controls (no thrombocytopenia)

Figure 3

Kaplan-Meier curve for the development of thrombocytopenia depending on baseline platelet count

Conclusion

Patients without haemato-oncologic diseases are at risk of linezolid-induced thrombocytopenia. especially those with bacteremia and low hemoglobin level. Patients with low baseline platelet count should be monitored closely early in therapy.

Disclosures

All Authors: No reported disclosures
405. Incidence and Potential Risk Factors of COVID-19 Associated Pulmonary Aspergillosis (CAPA)
Authors: Imoto Waki , Yamada Koichi , Kaneko Yukihiro , Kakeya Hiroshi
Published: November 2023

Background

Invasive pulmonary aspergillosis (IPA) that develops in coronavirus disease 2019 (COVID-19) patients is called COVID-19 Associated Pulmonary Aspergillosis, CAPA. The incidence of CAPA is reported as high as 1–40 % worldwide. However, the incidence of CAPA is highly variable among reports and it may vary among countries and medical facilities. Therefore, we investigated the incidence of CAPA in severe to critical severity COVID-19 using administrative claims data.

Methods

A retrospective cohort study was performed using administrative claims data called Diagnosis Procedure Combination (DPC) data from advanced treatment hospital in Japan to explore potential risk factors for CAPA using multivariable regression models. In addition, the contribution of CAPA to mortality in COVID-19 patients was examined.

Results

Data for 154,731 COVID-19 patients were included from DPC data. Of these, 33,136 were severe or critical COVID-19 and 14,720 were critical COVID-19. The incidence of CAPA were 0.4–1.3 % in severe or critical COVID-19, and 0.5–2.7 % in critical COVID-19. The risk factors for CAPA were steroids (hazard ratio [HR] = 4.753), immunosuppressants (HR = 2.592), intensive care unit admission (HR = 1.677), blood transfusion (HR = 6.206), and dialysis (HR = 2.185). The adjusted mortality HR for CAPA was 2.367 in severe or critical COVID-19, and 1.955 in critical COVID-19.

Conclusion

The incidence of CAPA in our study was lower than previously reported. It suggests the possibility that appropriate screening test is not being conducted in Japan due to insufficient attention to CAPA. Because CAPA is a significant contributor to mortality in COVID-19 patients, appropriate screening is required in at-risk patients.

Disclosures

Hiroshi Kakeya, MD, PhD, Asahi Kasei Pharma Corporation: Honoraria|Merck Sharp & Dohme: Honoraria|Sumitomo Pharma Co., Ltd.: Honoraria
458. Risk of COVID-19 and vaccine immunogenicity in pediatric solid organ transplant recipients – a single center study in South Korea
Authors: Baek Jee Yeon , Ihn Kyoung , Koh Hong , Lee Keum Hwa , Kim Min Young , Kim Sinyoung , Kang Ji-Man , Choi Jun Yong , Park Younhee , Kim Myoung Soo
Published: November 2023

Background

Solid organ transplant (SOT) recipients are at high risk for severe COVID-19 due to immunosuppressant (IS) use. Compared to adult SOT recipients (SOTRs), studies on risk and vaccination effectiveness in pediatric SOTRs are limited. We aim to investigate the epidemiologic characteristics of COVID-19 and vaccine immunogenicity in pediatric SOTRs.

Methods

This study was conducted at Severance Hospital in Korea, between 1999-2022. All SOTRs received SOT at the age ≤ 18 years were included. SOTRs who had a history of COVID-19 before SOT were excluded. Severe case was defined when there’s oxygen demand. Demographic data and information for risk factor exploration were retrospectively collected through chart review. Blood samples were collected prospectively after the COVID-19 vaccination policy for children was implemented. Humoral immunogenicity to WT, Delta and Omicron was investigated after 2 doses of BNT162b2 (BNT) using SARS-CoV-2 anti-S IgG titers, surrogate neutralization inhibition and plaque reduction neutralization tests. Post-vaccination samples of adult SOTRs were used as controls.

Results

A total of 118 SOTRs were included. The median age at SOT was 5 years (1-11 years), and the male to female ratio was 1:1.1. About 77% (91/118) had COVID-19 and 11% (10/91) of them were hospitalized for COVID-19 management. Four cases were severe cases and there was no death. The number of IS was significantly associated with the number of infection (p=0.04), distinct from hospitalization and severity (p=0.82 and 0.50), and there was no significant difference in outcomes between SOTRs received ≥ 3 doses of the COVID-19 vaccine and those received 0-2 doses (p=1.00, 0.21 and 1.00, respectively). Multiple logistic regression showed age at SOT and re-SOT as factors associated with number of COVID-19 (p=0.03, CI 0.36-0.96 and p=0.03, CI 1.74-6431.8). In vaccine immunogenicity analysis, humoral responses in pediatric SOTR were not lower than in adult SOTRs (table 1). However, the vaccine immunogenicity against Omicron was very poor compared to WT or Delta (figure 1).

Conclusion

Pediatric SOTR is susceptible to COVID, especially in older children at SOT and those who have undergone re-SOT. Two or Three doses of vaccination may be suboptimal for Omicron, so additional preventive measures are needed.

Disclosures

All Authors: No reported disclosures
463. Immunogenicity and Safety of mRNA-based SARS-CoV-2 vaccination in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review
Authors: Cardenas-Alvarez Jorge Luis , Triana Abel , Uribe Juan , Morgenstern-Kaplan Dan , Reynolds John M , Raja Mohammed , Natori Yoichiro
Published: November 2023

Background

Immunization is an effective strategy to decrease hospitalization and mortality related to SARS-CoV-2. Since the introduction of mRNA-based SARS-CoV-2 vaccines (BNT1261b2 and mRNA-1273), several studies have outlined the immunogenicity and safety of these in hematopoietic stem cell transplant (HSCT) recipients. Herein, we describe the first systematic review and meta-analysis with pooled data of available evidence on SARS-CoV-2 vaccination in this patient population.

Methods

We conducted a systematic review and meta-analysis of prospective cohort studies up to May 24 2022 in adult HSCT recipients who were vaccinated with ≥1 doses of either mRNA-based SARS-CoV-2 vaccine. The outcomes measured included: a) vaccine immunogenicity, b) safety, and c) breakthrough SARS-CoV-2 infections. Patients with solid organ transplant or prior documented history of SARS-CoV-2 infection were excluded.

Results

1084 unique studies were identified. After abstracts review, 81 full-text studies were assessed by two independent reviewers. Twenty-nine studies were included. A total of 1738 patients were analyzed, out of which 1478 received allogeneic-HCST (Allo-HSCT) and 260 autologous-HSCT (Auto-HSCT). Median IgG positivity after at least 1 dose of vaccination (among studies) was 77.3% (range: 0-100%) among Allo-HSCT and 91.7% (range: 60-100%) among Auto-HSCT. Cellular immunity was reported in 5 studies, describing IFN-gamma and/or lymphocyte response. Median positivity was 42% (range: 24-78%) among Allo-HSCT. Pooled incidence of adverse events reported among all HSCT recipients was 38.72%. The most common side effect was injection-site pain. No grade 5 adverse events were described. De-novo or exacerbation of graft versus host disease was reported in the median of 2.28% (range: 0-6.6%) of Allo-HSCT recipients. Breakthrough COVID-19 infections were reported in both Allo-HSCT and Auto-HSCT in 1/479 (0.2%) and 2/254 (1.29%), respectively.Figure 1.Pooled incidence of antibody positivity after one or more doses of mRNA-based SARS-CoV-2 vaccination in HSCT recipients

Conclusion

mRNA-based SARS-CoV-2 vaccination was immunogenic in HSCT recipients, particularly among Auto-HSCT recipients. One or more doses of mRNA-based vaccine elicited a greater humoral response, compared to that of cellular immunity. Adverse events were common, but often were mild. Breakthrough infections are rare after ≥ 1 doses.

Disclosures

John M. Reynolds, MLIS, Pfizer Inc: Stocks/Bonds
498. Covid-19 Hospitalization Rates in Kidney Transplant Patients Treated with Tixagevimab/Cilgavimab
Authors: Dugan Katherine , Casale Jillian , DeSanto Heather , Dowling Colleen , Smoke Steven
Published: November 2023

Background

Tixagevimab/cilgavimab (T/C) is a monoclonal antibody that was previously authorized for pre-exposure prophylaxis of COVID-19 in individuals with moderate to severe immune compromise. Limited evidence of safety and efficacy in immunocompromised populations was available at the time of authorization. The purpose of this study is to assess the safety and efficacy of T/C for pre-exposure prophylaxis of COVID-19 in a large cohort of kidney transplant patients.

Methods

This was a single-center Institutional Review Board-approved retrospective study. This study included adult patients that received a kidney transplant within the prior two years and received T/C between January 1, 2022, and March 31, 2022. The efficacy population comprised those that received the full 300 mg / 300 mg dose and the safety outcome population included those that received any amount of T/C. Patient demographics, transplant course history, and clinical interventions required during hospitalization due to COVID-19 infection were collected. The primary efficacy outcome was the rate of hospitalization for COVID-19 infection within 6 months of T/C administration. The secondary safety outcome was the rate of serious adverse events. Causality was assessed with the Naranjo algorithm.

Results

A total of 240 patients were reviewed for eligibility and 122 were included. A majority (60%) were male, 34% white and the median age was 57 (IQR 47-62) years old. The efficacy population included 115 patients. Most patients had hypertension (96%), decreased renal function (median CrCl 48 mL/min [33-63]), and had been vaccinated for COVID-19 (98%). The rate of hospitalization for COVID-19 infection within 6 months of T/C was 2% (2). The median time to hospitalization was 158 days. Neither patient required an ICU admission, mechanical ventilation, or experienced mortality. There was no incidence of heart failure, myocardial infarction, or anaphylaxis secondary to T/C. Other adverse effects (2%) considered possibly due to T/C included cardiac arrest (1) and atrial fibrillation (1).

Conclusion

Rates of COVID-19 hospitalization and adverse events within 6 months of T/C were low within a large cohort of kidney transplant patients.

Disclosures

All Authors: No reported disclosures
502. Telemedicine Service for Evaluation of Pediatric Outpatients at High Risk for Severe COVID-19
Authors: Weakley Kathryn E , Bryant Kristina
Published: November 2023

Background

During the COVID-19 pandemic, neutralizing monoclonal antibody (mAb) products received emergency use authorization for treatment of mild to moderate COVID-19 in high-risk patients. Expert consensus guidance recommended individualized risk assessment when considering mAb therapies in children and adolescents, as well as a process to ensure safe and timely administration. In one health system, high demand for mAb to treat adult patients, a finite supply, and a lower risk of severe COVID-19 in children led to allocation of a limited number of doses of mAb for pediatric use. The clinical outcomes of pediatric patients evaluated for allocation of mAb using telemedicine have not been well-described.

Methods

A pediatric infectious diseases (PID) telemedicine service was established to evaluate children with COVID-19 and adjudicate the administration of mAb based on risk assessment, symptoms, physical exam, and the availability of mAb product. Only PID providers were permitted to order mAb in pediatric patients. Demographics and clinical outcomes data were retrospectively collected from the charts of patients evaluated between August 1, 2021 and April 30, 2022.

Results

Two hundred sixty-seven patients were evaluated; 134 medical records have been reviewed to date. The average age was 14.7 years. The most common high-risk condition was obesity. The median time from onset of symptoms to telemedicine evaluation was four days. The median time from COVID-19 diagnosis to telemedicine evaluation was 1.5 days. Six patients were acutely referred to the emergency department (ED); three were admitted, one was given mAb and discharged, and two did not report to the ED as advised. Outpatient mAb was recommended for 12 patients; one declined and 11 received therapy with no serious adverse events. Only two of the remaining 116 untreated patients required COVID-related ED visits within 14 days of telemedicine evaluation; one was admitted with idiopathic thrombocytopenia and the other was discharged. All 134 patients made a full recovery.

Conclusion

Most children evaluated for mAb did not receive treatment and recovered. Telemedicine is a safe and effective way to evaluate patients with COVID-19. Individualized risk assessment can assist with allocation of scarce resources such as mAb.

Disclosures

Kathryn E. Weakley, MD, MSc, Pfizer: Grant/Research Support Kristina Bryant, MD, FPIDS, Enanta: Grant/Research Support|Gilead: Grant/Research Support|Oxford University Press: Royalties|Pfizer: Grant/Research Support
521. A phase II, double blind, placebo-controlled, randomized evaluation of the safety and efficacy of tafenoquine in patients with mild-moderate COVID-19 disease
Authors: Dow Geoffrey
Published: November 2023

Background

Tafenoquine is an 8-aminoquinoline antimalarial approved by the US FDA for malaria prevention and is being evaluated in clinical trials for potential use in other disease areas.

Methods

The safety and efficacy of tafenoquine administered as a 200 mg dose once per day on days 1, 2, 3, and 10 was evaluated over a 28-day period in mild-moderate COVID-19 patients. The primary endpoint was Day 14 clinical recovery from COVID-19 symptoms, defined as cough mild or absent, respiratory rate < 24 bpm, and no shortness of breath or fever. Following a successful futility analysis after n = 86 patients out of a target n = 275 were randomized, the study was terminated and unblinded early to facilitate planning for confirmatory studies.

Results

The proportion of patients not recovered on Day 14 was numerically decreased by 27% in the ITT population [8/45 v 10/42 not recovered in the tafenoquine and placebo arms, P = 0.60] and 47% in the PP population [5/42 v 9/41, P = 0.25]. Amongst individuals who recorded responses in an electronic diary at Day 28, all tafenoquine patients were recovered, whereas up to 12% of placebo patients exhibited lingering dyspnea. Time to clinical recovery from COVID-19 symptoms was accelerated in the tafenoquine arm by about 2-2.5 days. There were two COVID-19 related hospitalizations in the placebo arm and one in the tafenoquine arm. Mild, drug related adverse events occurred in 8.4% of individuals in the tafenoquine arm [v 2.4% in the placebo].

Conclusion

Although this trial was underpowered for the primary endpoint due to its early termination, the data are suggestive of a therapeutic benefit associated with tafenoquine administration in outpatients with mild to moderate COVID-19 disease, and larger studies are planned.

Disclosures

Geoffrey Dow, PhD, 60 Degrees Pharmaceuticals, INC: Board Member|60 Degrees Pharmaceuticals, INC: Inventor on Company covid + malaria patents|60 Degrees Pharmaceuticals, INC: Ownership Interest
614. Experience with Using MALDI-TOF MS to Diagnose Clinically Significant Filamentous Fungal Isolates
Authors: Murray Hugh , Crowe Amy
Published: November 2023

Background

Matrix assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF MS) technology has revolutionised bacterial diagnostics. Filamentous fungi are a varied and important group of pathogens that cause a wide spectrum of clinical disease. Identification of these traditionally relies upon highly experienced practitioners identifying unique fungal morphological characteristics, along with specific molecular techniques, but MALDI-TOF MS may be a useful alternative. The aim of this retrospective review was to determine how useful MALDI-TOF MS was as an adjunct to filamentous fungi identification at our laboratory service.

Methods

All fungal diagnoses made at St Vincent’s Pathology Melbourne, a large metropolitan laboratory servicing multiple tertiary hospitals and community pathology centres, from 2018 to 2022 were extracted. For clinically significant filamentous fungal isolates, the method of diagnosis was reviewed and categorised into; morphological diagnosis, Bruker MALDI Biotyper® diagnosis, and national reference laboratory diagnosis. All clinically significant isolates where MALDI-TOF MS was attempted were also reviewed.

Results

A total of 256 clinically significant isolates were extracted and reviewed. MALDI-TOF MS was attempted in 59 of these, with success in 39 (66.1%). Of the 20 cases where MALDI-TOF MS was attempted but did not identify the isolate, 16 were diagnosed morphologically and four required send out to the national reference laboratory. 71.2% of MALDI-TOF MS attempts were in the 2021-22 period when successful identification occurred 80.9% of the time. No species/genus appeared more or less readily identifiable. Of the remaining cases, 208 were identified morphologically and nine using the national reference laboratory.

Conclusion

MALDI-TOF MS performed modestly well at identifying filamentous fungi during this study period. Increased use and successful isolate identification in the 2021-22 period likely reflects improvement in the Bruker MALDI-TOF MS database for filamentous fungi. The MALDI-TOF MS system is a useful option in the identification of clinically significant filamentous fungi however morphological and molecular techniques remain important.

Disclosures

All Authors: No reported disclosures
616. Candidemia in a Dominican tertiary care hospital: Six years of history
Authors: Rojas-Fermin Rita A , Guzman-Marte Anel E , Sanchez-Marmolejos Ann Stephany , Cedeño-Bruzual Maria Fernanda , Rojas-Jiménez Javier , Rojas -Jiménez Marlon
Published: November 2023

Background

Despite the high mortality caused by invasive candidiasis or the fact that, as of 2022, a list of priority fungal agents was created by WHO, including Candida species in the three categories, global information is not robust, so it is difficult to estimate the distribution of these infections, species, antifungal resistance patterns, and clinical characteristics of the different types of patients affected globally.

Methods

We performed a retrospective review of patients with candidemia from 2017 to 2022. Data extracted from e-medical records from a teaching hospital with 289 beds included clinical and demographic information, co-morbidities, risk factors, antifungal resistance patterns, and outcomes.

Results

A positive rate of 0.75 percent was seen in 210 cases in 197 patients; 103 of them (52.28%) were men. With 52 cases each, 2021 and 2022 saw the most cases. In six years, the average age was 53 (IQR 54). The most frequent comorbidities were hypertension (52.79%), chronic pulmonary disease (45.68%), and nephropathy (31.98%). Intensive Care Unit stays (74.11%) and prior antibiotic exposure (92.89%) were the most prevalent risk factors, with statistical significance for length of stay in the ICU, the use of vasopressors, and central catheters (p 0.001). Surviving patients had a median length of stay of 26 days (p 0.001). The mortality rate for all patients was 49.2%. C. auris or C. krusei species were not isolated during the study period. The most frequently isolated species were C. tropicalis (40.4%), followed by C. parapsilopsis (23.8%) and C. albicans (20%). Fluconazole resistance was 6% (n=12) across all isolated species, with C. parapsilopsis having the highest prevalence 12% (n=6). C. tropicalis was the species most associated with death, followed by C. albicans.

Conclusion

In the post-pandemic period, we observed an increase in Candida isolates and noted a steady increase in cases of C. glabrata, especially in the ICU. Length of ICU stay, vasopressor use, and central catheters were seen as significant risk factors for candidemia, with older patients being the most affected as well as having higher mortality rates. Although C. auris hasn´t been detected at our institution, we recommend continued surveillance for our infection prevention program.

Disclosures

All Authors: No reported disclosures
625. Association of Eosinophilia with Parasites in Rhode Island Refugees, 2015-2020
Authors: Cruz-Sanchez Margarita , Marin Benjamin Gallo , Osorio Marcela , Teferi Maranatha , Ding Ann , Lorenz Matthew , Michelow Ian C
Published: November 2023

Background

Newly arrived refugees in the United States have high rates of parasitic infections that may contribute to morbidity and mortality. There is little consensus on testing for eosinophils to screen for parasites. We hypothesized that eosinophilia was a useful biomarker for various parasites that could help guide the management of refugees in the future.

Methods

We performed a retrospective chart review of all pediatric and adult refugees attending the only three refugee clinics in Rhode Island from 01/2015 to 12/2020. Individuals whose initial evaluation was delayed or took place in another state were excluded. Data were systematically collated in RedCap, and descriptive statistics were performed.

Results

Of 812 eligible refugees, 147 (18.1%) had eosinophilia ( ⪰ 450/uL). The majority of refugees (505, 62.2%) were from Africa, 242 (29.8%) from Asia, 32 (3.9%) each from the Americas, Europe, and 1 (0.1%) from Australia. Eosinophilia was mild (450-1499/uL) in 113 (76.9%), moderate (1500-4999/uL) in 30 (20.4%), and severe ( ⪰ 5000/uL) in 4 refugees (2.7%)(Table 1). The prevalence of symptoms ranged from none (bloody stools) to 17.1% (abdominal pain). 48 (32.7%) refugees with eosinophilia tested positive for a parasite in their stool by O&P and/or PCR assay. The most prevalent organisms were Giardia (n=25) and Blastocystis hominis (n=22). An additional 22 (15%) tested positive for Schistosoma or Strongyloides (Table 2). Forty-six (31.3%) refugees with eosinophilia were treated with antiparasitic agents. Sixty-three (42.9%) had no follow-up eosinophil tests. Of the 84 patients who did have monitoring of their eosinophilia during the first year after arriving in the US, eosinophilia resolved in only 53 (64.6%). One patient (0.7%) had a severe complication: Strongyloides hyperinfection syndrome. Five patients (3.4%) received alternative diagnoses that explained their eosinophilia, including eczema, myelofibrosis, and a drug allergy.

Conclusion

Eosinophilia occurred in almost 1/5 of newly arrived refugees in RI. Diagnostic, therapeutic, and follow-up practices varied substantially. Approximately 1/3 of evaluable refugees had persistent eosinophilia at one year. A standardized screening approach for eosinophilia is needed to inform appropriate management.

Disclosures

All Authors: No reported disclosures
636. Epidemiology and Outcome Among the Elderly Hospitalized Patients with Respiratory Syncytial Virus Infections
Authors: Bhargava Ashish , Szpunar Susan M , Malik Ambreen , Tehaili Hussein , Sharma Mamta
Published: November 2023

Background

Elderly patients with congestive heart failure (CHF), chronic lung diseases (CLD) and immunocompromised conditions are considered a high-risk category for severe respiratory syncytial virus (RSV) infections. Our study aimed to identify RSV disease epidemiology and its outcomes among the elderly hospitalized patients with and without high-risk conditions (HRC).

Methods

We conducted a multicenter historical cohort study of adult patients for laboratory-confirmed RSV-related diseases in Ascension hospitals in southeast Michigan between January 2017 and December 2021. Patients were identified using ICD 10 codes for RSV diseases. Patients with HRC were those elderly patients with CHF, CLD and immune-compromised conditions. Data were analyzed using SPSS v. 29.0.

Results

Among 240 patients, 31.3% (75) were without HRC whereas 68.7% (165) had at least one HRC. The mean (sd) age of the patients without HRC was 81.9 + 8.9 years, 47 (62.7%) were female, 52 (69.3%) were white and mean body mass index (BMI) was 28.9 + 8.3 years. The mean (sd) age of the patients with HRC was 76.6 + 7.7 years, 111 (67.3%) were female, 125 (75.8%) were white and BMI was 29.8 + 9.0 years. Major comorbidities among patients without HRC compared to those with HRC were hypertension (77.3% vs 69.1%), cerebrovascular condition (25.3 vs 10.9%), diabetes (18% vs 37.6%), dementia (21.3% vs 8.5%), and chronic kidney disease (CKD) (16% vs 21.2%). Current smokers were 30.7% vs 66.1% among patients without HRC compared to those with HRC. On admission, median (IQR) qSOFA scores were 0 (0-2) vs 1 (0-3) among patients without HRC compared to those with HRC. Lower respiratory tract infections (LRTI) were 32% vs 43%, acute kidney injury (22.7% vs 24.2%), liver injury (1.3% vs 3%), mechanical ventilation (6.7% vs 9.1%), pressors (1.3% vs 1.8%), and ICU requirement (10.7% vs 15.2%) among patients without HRC compared to those with HRC. In-hospital mortality were 1.3% vs 5.5% among patients without HRC compared to those with HRC.

Conclusion

In our study, elderly patients with HRC were younger, smokers with higher incidence of diabetics, CKD, higher qSOFA on presentation with higher LRTIs, and other complications including mortality. Targeted risk mitigation strategies can help reduce disease burden and cost associated with RSV infections.

Disclosures

All Authors: No reported disclosures
666. Evaluation of Vancomycin Harms for Intra-abdominal Infections
Authors: McCoy Christopher , Yan Xuping , Chapin Ryan W , Donohoe Kendall
Published: November 2023

Background

The Infectious Diseases Society of America recommends broad spectrum Gram-negative and anaerobic coverage for complicated intra-abdominal infections (IAI). Gram-positive beta lactam resistant organisms such as methicillin-resistant S. aureus (MRSA) are not typically associated with pathogenicity. Vancomycin, an empiric Gram-positive agent, is associated with nephrotoxicity. This study evaluated incidence of harm in patients treated with antimicrobial regimens which included vancomycin vs. those which did not.

Methods

This single center, retrospective cohort study included adult inpatients admitted between September 1, 2018 and September 30, 2022 with a diagnosis of IAI. Patients with concomitant MRSA infection from a different site or who received hemodialysis or continuous renal replacement therapy were excluded. The primary outcome was the rate of renal toxicity in patients treated empirically for IAI. Secondary outcomes included duration of treatment, duration of hospitalization, and evaluation of guideline concordant use of vancomycin in IAI.

Results

Of 61 included patients, 39 (64%) were treated empirically with vancomycin for IAI. Patients on vancomycin experienced more acute kidney injury compared to those on empiric standard regimens [9/39 (23%) vs. 1/22 (5%), p=0.05]. Median duration of hospitalization for patients on vancomycin vs. standard therapy was 11 days (IQR, 14) vs. 5 days (IQR, 4), p < 0.05, respectively. Median length of inpatient therapy was 9 days (IQR, 12) vs. 4 days (IQR, 5), p < 0.05, for patients on vancomycin vs. standard therapy. Notably, non-guideline concordant use of vancomycin occurred in 14/39 (46%) patients and no patients had cultures grow MRSA.Table 1.Baseline CharacteristicsTable 2.Primary and Secondary Outcomes

Conclusion

More patients who were treated with vancomycin experienced acute kidney injury. Patients who were treated with standard therapy were more likely to have a reduced hospital length of stay and shorter inpatient antibiotic duration of treatment. Institutional guidelines recommend no additional coverage outside of specific risk factors but stewardship efforts do not extend to this use. Future efforts to decrease use of vancomycin for IAI may result in a decrease in observed harms. Further studies are needed to refine which patients may truly benefit from empirical vancomycin therapy.

Disclosures

All Authors: No reported disclosures