bluuebunny/crossref_metadata_2025 huggingface dataset:
P-2330. Herpes Zoster in Mexican Patients With Cancer. Clinical Features, Complications and Economic Burden
Authors: Fernandez Pamela Alatorre , Osorio López Erick Antonio , Guerrero Maura González , Zúñiga Antonio Camiro , Islas-Muñoz Beda , Volkow-Fernández Patricia , Juarez Patricia Cornejo
Published: January 2025

Background

Herpes zoster (HZ) typically causes a painful, unilateral, vesicular rash that affects one dermatome. In immunocompromised, it can disseminate and cause postherpetic neuralgia. The incidence of HZ has increased in recent years, especially in elderly and immunocompromised people, cancer patients included. Mexico has a low vaccination rate with no policy for patients at high risk for HZ.

Methods

Between 2021 and 2023, all patients with HZ identified at our Tertiary Cancer Institute were included. Demographics, clinical manifestations, therapeutics, and complications were registered. To determine the economic burden of the disease, an economic analysis was done.

Results

280 cases of HZ were identified. 164 (59%) women; median age 57 years (IQR 45-67.5). 200 solid tumors (71%) mainly breast cancer (n=72, 26%). Eighty hematological malignancies (HM) (29%), lymphoma the most frequent (n=51, 18%). 77 disseminated HZ, 62 (22%) cutaneous and 11 (4%) in CNS. 77 cases (27.5%) were treated outside of our institution. In 154 cases (55%), ambulatory therapy was prescribed, and 49 (17.5%) were treated in-hospital [median hospital stay: 8 days (IQR 5-13)]. In 45 (16%) patients, HZ delayed oncological treatment. One patient died.

Bivariate analysis comparing outpatients vs. hospitalized was significant for PLHIV (p=0.001), HM (p=0.002), chemotherapy in the previous month (p=0.022), chronic steroid (p=0.009), infection that precedes HZ (p=0.003), and disseminated zoster (p=0.001). Older age, high blood pressure, and disseminated HZ were related to the development of postherpetic neuralgia [OR 1.036 (1.006-1.066), 3.637 (1.541-8.580) and 2.961 (1.306-6.717)].

The estimated cost of care during the three years was USD 208,304.05. The average cost of care was USD 743.94. The bivariate analysis is presented in Table 1. Healthcare cost of attention is presented in Table 2.

Conclusion

HZ in this oncologic center is a growing concern. The projection of the potential increase in cases for 2024 estimates 173 new cases, which will represent USD 128,419.45.

The most affected groups were patients with breast cancer, hematological malignancies, chronic steroid use, PLHIV, and those over 50 years of age. Our study's data will help enforce HZ vaccination in oncological patients and PLHIV.

Disclosures

All Authors: No reported disclosures
P-2332. Pre to Post COVID-19 pandemic: Analyzing Recovery of Respiratory Viral Circulation Patterns
Authors: El Haddad Kim , Liu Wei , Burke Patrick , Esper Frank
Published: January 2025

Background

The COVID-19 pandemic and resulting worldwide countermeasures immediately impacted the circulation of endemic respiratory viruses. Yet the dynamics of recovery have varied between species. We hypothesize the level of disruption in virus circulation and the time to return to pre-pandemic norms is dependent on circulation overlap with the pandemic strain.

Methods

Interrupted time series (ITS) analysis and continuous wavelet analysis of univariate times series (Morlet) was conducted on Cleveland Clinic respiratory virus results from 2015 through 2023. Data was analyzed on individual virus species grouped in 3 seasonality patterns: wintertime (FLUA, FLUB, RSV), springtime (HMPV, PIV3) and year-round (ADENO, RHINO/ENTERO). Pre and post pandemic trends in positivity, peak shift analysis and periodic cycle were assessed.

Results

FLUA positivity dropped by 11% (95% CI 7.4-14%) in first effective quarter post-pandemic and gradually increased (+1.9% per year, p=.046) afterwards. The dominant cycle shifted from annual pre-pandemic to semiannual, with virus incidence peaks (median week) at 21-W50, 22-W17, and 22-W51, respectively, departing from the pre-pandemic baseline (W7, p < 0.001). RSV positivity decreased by 2.6% per year after the pandemic (95% CI 1.2-4.0%). The annual cycle remained dominant, but peak incidence of RSV shifted earlier then gradually normalized (baseline-W1 vs. 21-W39 vs. 23-W45, p< .0001). FLUB positivity significantly decreased postpandemic (0.18% vs 6.1%, p< .0001). No significant impact on PIV3 and HMPV positivity occurred. Both viruses showed an annual cycle dominance throughout, with a semiannual cycle only observed post-pandemic. ADENO showed decreasing trends before the pandemic and increasing trends after the pandemic (-0.63% vs +0.94%, p=.001). Both ADENO and RHINO/ENTERO did not show changes in circulation with no distinct peaks observed.

Conclusion

Pandemic circulation disproportionately affects co-circulating viruses. Wintertime dominant viruses experienced prolonged displacement and have yet to return to pre-pandemic norms. Conversely, spring and year-round viruses were only modestly displaced and are now near pre-pandemic baseline. This study holds important implications for public health preparedness for future pandemics.

Disclosures

All Authors: No reported disclosures
P-2336. Efficacy of Treatment Regimens in Achieving Virological Response in Patients with Hepatitis D Virus Infection: A Network Meta-analysis
Authors: Ouranos Konstantinos , Mylona Evangelia K , Dellis Charilaos , Bakaloudi Dimitra Rafailia , Shehadeh Fadi , Kalligeros Markos , Mylonakis Eleftherios
Published: January 2025

Background

Despite the availability of treatment options for hepatitis D virus (HDV) management, choosing the most appropriate drug scheme for achieving virological response (VR) has not been adequately studied.

Methods

We conducted a systematic review and network meta-analysis of randomized trials in PubMed, EMBASE, and Web of Science databases reporting rates of VR (defined as undetectable HDV RNA or decrease by ≥ 2 log10 IU/ml at the end of treatment compared with baseline measurements). Available treatment regimens included interferon-alpha (IFN-alpha), pegylated IFN-alpha (PEG-IFN-alpha), nucleoside analogs (NA), bulevirtide (BLV), lonafarnib (LNF), combination therapy or placebo. We used random effects model and estimated odds ratio (OR) with 95% confidence interval (CI) to compare treatments based on VR. To identify the best treatment, we estimated the surface under the cumulative ranking (SUCRA) curve. Analyses were performed using the meta and netmeta packages in R (version 4.3.3).

*Denotes statistically significant associations

Results

A total of 1322 patients from 21 studies were included in the analysis and were randomized in one of 11 treatment interventions, as described in Figure 1. Treatment duration ranged from 24 to 96 weeks. BLV + PEG-IFN-alpha was ∼6 times more likely to result in VR compared with BLV alone (OR, 5.55 [95%CI: 1.60, 19.25]). Treatment with BLV + PEG-IFN-alpha was ∼17 times more likely to result in VR compared with PEG-IFN-alpha monotherapy (OR, 16.7 [95%CI: 5.6, 49.5]) (Table 1), the main agent recommended by official guidelines for HDV management. Based on probability ranking, the most effective drug schemes for achieving VR at the end of treatment were BLV + PEG-IFN-alpha (99.7%), BLV + NA (84.4%), BLV (78%), and PEG-IFN-alpha (61.3%).

Conclusion

BLV + PEG-IFN-alpha is superior in achieving VR at the end of HDV treatment compared with all other available drug schemes. Further research to determine whether BLV + PEG-IFN-alpha can maintain long-term VR after end of treatment is needed. Studies should also evaluate the impact of different BLV dosages on VR.

Disclosures

Eleftherios Mylonakis, MD, PhD, BARDA: Grant/Research Support|Basilea: Advisor/Consultant|Chemic Labs/KODA Therapeutics: Grant/Research Support|Cidara: Grant/Research Support|Leidos Biomedical Research Inc./NCI: Grant/Research Support|NIH SciClone Pharmaceuticals: Grant/Research Support|NIH/NIAID: Grant/Research Support|NIH/NIGMS: Grant/Research Support|Pfizer: Grant/Research Support|Regeneron Pharmaceuticals, Inc.: Grant/Research Support
P-2340. Single-Center Inpatient Measles Analysis During a Congregate Setting Outbreak; Comparing Vaccine History between Measles Positive and Negative Cohorts
Authors: Fricchione Marielle J , Nguyen David , Nash Colleen B
Published: January 2025

Background

Chicago’s 2024 measles outbreak affected many new arrivals living in congregate settings with unknown or poorly documented vaccination history. Despite post-exposure prophylaxis provided at shelters, many families still developed measles. Frequency of measles exposure in congregate settings certainly plays a role in infection, but vaccination history and source should also be evaluated.Table.Characteristics of Measles Patients Under Investigation (PUI) stratified by PCR result

* One case received IGIM and five received 1 MMR post-exposure prophylaxis dose given at the shelter between 10—30 days prior to rash onset (median: 11 days), ∞ including vaccine strain case, # n=7, ^n=10, ^^Countries of origin: Venezuela, Peru, Ecuador

Methods

Data was abstracted from 12 measles PCR positive and 13 measles PCR negative patient charts from 3/10/24—4/23/24 including measles vaccination history, IgG antibody titers, concurrent infections and measles complications. Relative risks and p-values were calculated using MedCalc Software Ltd (Version 22.023).

Results

From 3/10/24—4/23/24, 12 measles PCR positive patients were admitted with median age 16 years (range 13 months—43 years) including 3 parent-child dyads; serotyping through the Illinois Department of Public Health reported one vaccine strain and 11 wild type cases. Of the 11 wild type measles cases, 3 (27%) had concurrent infections; (2 of 3 group A streptococcus culture positive (oropharynx); 1 of 3 was rhinovirus/enterovirus positive (nasopharyngeal PCR); 8 of 11 (73%) had at least 1 measles complication including dehydration (4), acute otitis media (3), pneumonia (1), and hepatitis (2). Comparing vaccine history between measles negative and positive cohorts, there was a non-significant trend towards history of international vaccination in the measles positive cohort. History of current congregate setting residence and exposure to a known measles case were significantly associated with measles positivity with a relative risk of 2.2.

Conclusion

Inpatient data is lacking during the 2024 international measles surge and new arrivals' vaccination history documentation is inconsistent. A trend towards international measles vaccine receipt in a measles positive cohort highlights the importance of US public health efforts to offer MMR vaccination to new arrivals. Limitations of this report include small cohort sizes and recall bias. Additional data is needed to describe the impact of improper vaccine storage and handling on vaccine effectiveness in the current international measles epidemic.

Disclosures

All Authors: No reported disclosures
P-2341. Was Viral Interference Responsible for the Unusual 2021-22 Influenza Season?
Authors: Krauland Mary G , Roberts Mark S
Published: January 2025

Background

Viral interference is a short-term, non-specific immunity that limits infection by a second virus when a person has been infected by a first virus. Epidemiological and biological data supports the existence of viral interference, most likely caused by interferon production in response to an infection. The 2021-22 influenza season in the US displayed a highly unusual pattern in which a single influenza variant displaying a bimodal pattern, with a fall rise in transmission followed by a winter decrease and subsequent increase. The addition of a refractory period to a simulation of co-circulation of an Omicron-variant COVID-19 like virus and an H3N2-like influenza virus produced similar transmission dynamics to that observed in the 2021-22 influenza season.Figure 1. Covid-19 Omicron variant and influenza cases in the US population and in the simulation.A: Reported Covid-19 Omicron variant and influenza cases in US in the 2021-22 season. B: Simulated COVID-19 and influenza cases with and without refractory period with varied prior immunity to COVID-19. Left Y-axis, influenza cases; right Y-axis, Covid-19 cases.

Methods

We used the Agent-based modeling platform FRED (Framework for Reproducing Epidemiological Dynamics), with inclusion of a model of Omicron-variant COVID-19 like virus and an H3N2-like influenza virus.

Results

In a simulation including a 7-day refractory period, the introduction of an Omicron-like variant in December of the season after influenza transmission was already widespread caused influenza transmission to subside while the Omicron-like variant was circulating at high rates. Influenza still circulated at lower levels and rebounded after the Omicron-like variant surge decreased since there was no cross-immunity between the 2 viruses and a large pool of influenza susceptible agents remained. The epidemic curve from this simulation resembled in shape the epidemic curve of H3N2 influenza in 2021-22 (Figure).

This effect was not present in similar simulations without a refractory period and was similar over the values of prior population immunity included in the simulation set.

Conclusion

Viral interference caused by widespread COVID-19 Omicron variant transmission is a plausible explanation for the unusual influenza infection pattern seen in the 2021-22 season. It is likely that viral interference is often influential in the interactions of a number of respiratory pathogens and should therefore be included in simulations that include multiple co-circulating respiratory pathogens.

Disclosures

All Authors: No reported disclosures
P-2344. Genomic Analysis of Monkeypox Virus (MPVX) Outbreak in Bangkok, Thailand in 2022-2023
Authors: Putcharoen Opass , Rattanatumhi Khwankamon , Supataragul Ananporn , Sangsub Pakamas , Wacharapluesadee Supaporn
Published: January 2025

Background

Since early May 2022, cases of mpox (monkeypox) have been reported in countries where the disease is not endemic, alongside continued reports from endemic regions. This marks the first time that multiple mpox cases and clusters have been concurrently reported in both non-endemic and endemic countries across diverse geographical areas. As of March 8, 2024, there were 94,776 confirmed mpox cases globally, with 721 cases in Thailand—most of which were reported from Bangkok.

Figure 1

The phylogenetic tree was constructed from 60 Mpox genomes collected in Bangkok, Thailand, during 2022-2023. The tree was produced using the maximum likelihood method in IQ-TREE2 with 1000 replicates of ultrafast bootstrap and HKY+F+I nucleotide substitution model and visualized by ggtree library in R.

Methods

We collected biological samples, mostly lesion swabs from suspected Mpox cases at STI Clinics in Bangkok, Thailand, from July 2022 to September 2023. Whole Genome Sequencing (WGS) was performed on 60 specimens from mpox cases in Bangkok, primarily lesion swabs, that were PCR-positive for MPXV with a cycle threshold (Ct) value below 30. A hybridization probe-capture–based approach was utilized for sequencing, specifically Illumina RNA Prep with Enrichment kit with the Viral Surveillance Panel. Consensus genomes were generated using an in-house pipeline based on reference mapping (BWA v0.7.17) to the Mpox reference genome from Nigeria (GenBank accession no. NC_063383.

Results

Phylogenetic analysis from WGS revealed that the predominant MPXV clade in Bangkok is IIb, with most specimens belonging to lineage IIb-C (48/60), followed by IIb-A (9/60) and IIb-B (3/60) as shown in Figure 1. Lineage IIb-A was detected in samples from 2022, while IIb-B and IIb-C were prominent in 2023. We identified multiple clusters with similar genomes in lineage IIb-C from different individuals, with percent identity ranging from 99.970% to 99.999% (197,184 nucleotides), suggesting ongoing community transmission. There is no clear introduction of lineage IIb-C into Thailand, however, the phylogenetic tree indicates the transmission of locally transmitted lineage to other countries. We detected the unique activity of APOBEC mRNA editing in serial samples from immunocompromised hosts. No mutations associated with resistance to tecovirimat were identified.

Conclusion

Our study demonstrated the introduction of MPXV from multiple countries, confirming ongoing community transmission in Bangkok during 2022-2023. Continuing genomic surveillance is crucial for tracking the epidemiology and viral evolution.

Disclosures

All Authors: No reported disclosures
P-2348. Predictors of Dengue Outcome after Adoption of a Management Protocol
Authors: Sigdel Keshav Raj , Pradhan Rehan , Lamichhane Saugat , Ranjitkar Nora , Koirala Janak
Published: January 2025

Background

Dengue caused a large outbreak in Nepal with over 54,000 reported cases in 2022. Once considered a disease of tropics, dengue has expanded to subtropical and temperate regions of Nepal including Kathmandu valley. A standard protocol, which included screening criteria for admission and treatment based on severity, was adopted at our hospital which is located at the epicenter of 2022 outbreak.

Methods

We enrolled 261 patients admitted to Patan Academy of Health Sciences between August and October, 2022. We analyzed patients’ baseline clinical and laboratory characteristics as predictors of outcomes including duration of stay and mortality.

Results

The mean age of the patients was 40.9 (±19.1) years with female predominance (54.4%). Most patients were from Lalitpur district followed by Kathmandu, which are the main catchment areas of the hospital and epicenter of 2022 outbreak. Most common clinical presentations included fever (93.5%),followed by vomiting (65.5%), myalgia (52.1%), headache (45.6%), mucosal bleeding (18.4%), eye pain (16%), anorexia (13.8%), loose stools (13.8%), and rash (10%). The patient’s age correlated directly with both systolic and diastolic blood pressures (p=0.002 and 0.01, respectively), and inversely with platelet counts (p=0.002).

Duration of hospital stay (median 3, IQR 2 days) correlated with aspartate aminotransferase (median 141 U/L) and alanine aminotransferase (median 90.5 U/L) levels at presentation (p< 0.001 and p=0.03, respectively). Hemorrhagic rash occurred in 10 patients and was associated with low platelets at day 1 of admission (p=0.01). There were no deaths.

Conclusion

Elevated aminotransferases as a marker of hepatocellular injury was the main predictor of longer duration of hospital admission. With adoption of a standard screening and treatment protocol, despite varied clinical presentations and complications, no fatalities occurred among the 261 adult patients in our hospital. This underscores the importance of early detection and proper management in effectively combating the disease and preventing mortality.

Disclosures

All Authors: No reported disclosures
P-2351. Assumptions and Realities: Unraveling Varicella Zoster Virus Immunity in Unvaccinated Populations
Authors: Jordão Sofia , Pena Eduarda , Gonçalves Maria João , Batista Clara , Oliveira Susana Ramos , Azeredo Constança , Araújo Sara , Reis Fábio , Soeiro Cristina , de Abreu Ricardo Correia
Published: January 2025

Background

In countries without universal vaccination for chickenpox in childhood, a very high seroprevalence for varicella zoster virus (VZV) IgG in adults is often assumed. Consequently, some suggest vaccinating at-risk adults against herpes zoster, even if they lack a documented history of chickenpox, under the assumption of immunity. However, this presumption may not accurately reflect today's epidemiological landscape. Neglecting the risk of primary infection post-childhood could lead to severe outcomes in vulnerable adults, pregnant patients, and increase the likelihood of exposure for caregivers, potentially resulting in secondary transmission.

Graphic 1. Sample distribution by gender and age group.

Methods

A retrospective study was conducted on VZV serology among individuals aged 11 and above, from February 2014 to March 2024, who were unvaccinated and lacked known chickenpox history, within a Portuguese hospital.

Graphic 2. Varicella Zoster Virus IgG seroprevalence by gender and age group.

Results

Analysis of 613 patients (68% women, median age 39 years), all with high VZV infection risk due to comorbidities or immunosuppression, revealed an 83.6% VZV IgG positivity rate, increasing with age. Among working age individuals aged 21-60,12% were seronegative for VZV and 19.2% of women of childbearing age 16-40 showed no immunity.

Conclusion

Although common, the presence of antibodies against VZV is not universal after childhood in unvaccinated populations. Vaccination for herpes zoster is not indicated for the prevention of primary infection, so assuming immunity may fail to prevent it in a population at risk. Prevention of chickenpox relies on specific vaccination, or the use of immunoglobulin when the former is contraindicated, which implies recognition of this susceptibility. Serology remains a useful tool, especially for at-risk individuals and caregivers, and should be considered in women of reproductive age and immunocompromised individuals.

Disclosures

All Authors: No reported disclosures
P-2352. Post-pandemic SARS-CoV-2 vaccination and infection status and risk of influenza-like illnesses and work absenteeism in healthcare workers – a prospective cohort study
Authors: Dörr Tamara K , Lacy Joanne , Ballouz Tala , Cusini Alexia , Grässli Fabian , Haile Sarah , Kocan Emina , Carsten Möller J , Puhan Milo Alan , Schlegel Matthias , Von Kietzell Matthias , Rütti Markus , Stocker Reto , Vuichard-Gysin Danielle , Kahlert Christian , Kuster Stefan , Kohler Philipp
Published: January 2025

Background

In the transition to SARS-CoV-2 endemicity, we prospectively assessed whether the number of SARS-CoV-2 vaccinations was associated with influenza-like illness (ILI) episodes or work absenteeism in a cohort of healthcare workers (HCW).

Methods

In October 2023, we updated information on SARS-CoV-2 vaccination and infection within a prospective multi-centre HCW cohort. Anthropometric data and information on personal health, patient contact, and household structure were collected. Between 11/2023 and 04/2024 (i.e. follow-up), where community activity of SARS-CoV-2 and influenza were high, HCW filled in weekly questionnaires on acute viral symptoms and number of days absent from work. The main predictor was SARS-CoV-2 vaccination status grouped into unvaccinated, 1-2, 3, or≥ 4 vaccine doses. Outcomes were the number of ILI episodes and days absent from work. ILI was defined as acute-onset (≤ 7 days) of fever/feverish feeling and one respiratory symptom (runny nose, loss of smell, cough, sore throat). Using a negative binomial model, we calculated adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) for SARS-CoV-2 vaccination status and the outcomes, adjusting for important confounders.

Results

We included 1’783 HCW (median 47 years, range 17-70), 178 (9.9%) were unvaccinated, 368 (20.6%) had 1-2 vaccinations, 910 (51.0%) 3 vaccinations and 327 (18.3%) ≥4 vaccinations (Table 1). Overall, 764 (42.8%) experienced ≥ 1 ILI episode during follow-up, the mean number of days absent from work was 2. In multivariable analysis, number of SARS-CoV-2 vaccinations was positively associated with number of ILI episodes (aIRR per dose 1.15, 95% CI 1.13-1.16), as did the number of positive SARS-CoV-2 tests (aIRR 1.13, 95% CI 1.11-1.16). Seasonal influenza vaccination (aIRR 0.80, 95% CI 0.77-0.83) was associated with decreased risk (Table 2). SARS-CoV-2 vaccination was also associated with days absent from work (aIRR 1.08, 95% CI 1.06-1.10).

Conclusion

The number of vaccinations against SARS-CoV-2 is not associated with decreased ILI episodes and absenteeism in HCW during high community transmission level of SARS-CoV-2 and influenza. In contrast, smoking and male sex are associated with increased and influenza vaccination with decreased risk.

Disclosures

Tala Ballouz, MD PhD, Moderna: Grant/Research Support
P-2360. Wastewater-Based Surveillance of Hepatitis A Virus Across Communities in Alberta, Canada
Authors: Weyant Benson , Ueno Aito , Waddell Barbara Jean M , Lee Jangwoo , Xiang Kevin , Du Kristine , Bender Aidan , Visser Gail , McCalder Janine , Papparis Chloe , Chavarriaga Maria Bautista , Fonseca Kevin , Swain Mark , Coffin Carla , Lee Bonita , Pang Xiao-Li , Drews Steven J , O’Grady Christine , Hubert Casey R J , Parkins Michael
Published: January 2025

Background

Hepatitis A virus (HAV) incident infection in Canada is rarely diagnosed (i.e. incidence of 3.6-10 cases/100,000 persons) (PMID: 18159360). Infections generally relate to imported contaminated food-products, or travelers returning from endemic countries. Due to its fecal-oral spread, possible underdiagnosis, and often-cryptic presentation, HAV is an ideal candidate for wastewater (WW)-based surveillance, a tool increasingly utilized to monitor infectious diseases globally.Figure 1.Longitudinal monitoring of HAV RNA wastewater abundance across eight Alberta municipalities over a 4-month period.

Methods

24-hour composite WW was collected weekly from eight geographically disparate, and socioeconomically diverse municipal WW treatment plants in Alberta from August to December 2023. After short-term cold storage, WW was centrifuged, and RNA from the raw pellet was extracted using Qiagen’s RNeasy PowerFecal pro. HAV levels were quantified by RT-qPCR of the vp1 gene. 2021 Canadian census data was used to define population demographics for each participating site.

Results

HAV was detected in 18/117 (15.4%) WW samples and 5/8 (62.5%) municipalities over the 4-month period (Figure 1). RNA abundance in HAV positive WW samples was a median of 3.4 copies/mL (IQR 0.44 - 6.97). Larger population size (p=0.007), and greater density (p=0.001) were associated with increased likelihood of HAV WW detection, whereas social and economic demographics of populations within sewershed catchments did not associate with likelihood of HAV detection (Table 1).

Conclusion

HAV RNA is rarely detected in the wastewater of Alberta. Detection was more frequently observed in larger municipalities, which is consistent with non-endemic, imported disease. WW surveillance can potentially be adapted to monitor HAV in the context of outbreaks to reduce secondary transmission, and safeguard public health.

Disclosures

Mark Swain, MD MSc, Abbott: Advisor/Consultant|Advanz: Advisor/Consultant|Gilead, BMS, CymaBay, Intercept, Genfit, Pfizer, Novartis, Astra Zeneca, GSK, Celgene, Novo Nordisk, Axcella Health Inc., Merck, Galectin Therapeutics: Grant/Research Support|GSK: Advisor/Consultant|Ipsen: Advisor/Consultant|Novo Nordisk: Advisor/Consultant Carla Coffin, MD MSc, Altimmune: Grant/Research Support|Gilead: Grant/Research Support|GSK: Grant/Research Support|Janssen: Grant/Research Support Steven J. Drews, PhD FCCM D(ABMM), Abbott: Grant/Research Support|Danaher: Honoraria|Roche: Advisor/Consultant|Roche: Grant/Research Support
P-2362. Risk Factors for Persistent and Recurrent CMV DNAemia in a Real-World Cohort of SOT and HSCT Patients Receiving Maribavir
Authors: Morinishi Chelsea , Schaenman Joanna M , Beaird Omer E , Gaynor Pryce , Multani Ashrit , Pham Christine , Yanagimoto-Ogawa Lauren
Published: January 2025

Background

Refractory/resistant (R/R) CMV infection, defined by persistent symptoms or DNAemia after at least two weeks of antiviral therapy, is associated with high rates of rejection and mortality in transplant patients. Maribavir (MBV) is a newer agent with demonstrated efficacy in achieving DNAemia clearance without the bone marrow suppression associated with conventional first line therapy. However, there is less data on the risk factors for treatment failure with MBV. We sought to evaluate clinical outcomes of MBV in transplant patients in a real-world patient cohort.Table 1:Demographic Characteristics

Methods

A retrospective chart review was conducted of adult solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients who received MBV for R/R CMV infection at a high-volume transplant center from 2021-2023. The main treatment outcome was failure (defined as persistence of DNAemia requiring a switch in therapy).Table 2:Risk Factors for Maribavir Failure

Results

Nineteen patients received MBV for CMV DNAemia or tissue-invasive disease. Overall, 84% were SOT, 63% had high-risk CMV serostatus, and 90% had asymptomatic DNAemia. Twenty-six percent of patients experienced MBV failure. The median absolute lymphocyte count (ALC) was 852 µL at MBV switch in those with successful treatment compared with 262 µL in those with MBV failure, although this did not reach statistical significance. Peak viral load was also not significantly associated with MBV failure. Five patients later developed MBV resistance by commercial genotype sequencing.

Conclusion

Real world use of MBV demonstrated comparable rates of viral clearance with clinical trial data in SOT and HSCT patients. While not statistically significant, there was a trend towards MBV failure in patients with lower ALC. Future studies may be useful to determine if switching to MBV before onset of worsening lymphopenia related to first line therapy would impact the rate of treatment failure and MBV resistance. The lack of association between VL and virologic response also suggests that MBV may be safely used in patients regardless of viral load.

Disclosures

Joanna M. Schaenman, MD, PhD, FAST, Eurofins Viracor: Honoraria|F2G: Grant/Research Support|MedCure: Advisor/Consultant|Moderna: Clinical trial support to institution|OneLegacy: Advisor/Consultant
P-50. Mpox Vaccine Uptake Among Sexual and Gender Minority Veterans With and Without HIV in a Nationwide US Veteran Cohort
Authors: Van Epps Puja , Meriwether Wyatt E , Mcconnell Alex , (Lexi) Matza Alexis , Shipherd Jillian , Kauth Michael R
Published: January 2025

Background

Sexual and gender minorities (SGM) and people with HIV have been disproportionately affected by the Mpox pandemic. Vaccination is recommended for those who may be at an increased risk. We examined the uptake of Mpox vaccine nationally in the Veterans Health Administration (VHA) among SGM Veterans and reported on disparities across groups.

Methods

We queried VHA’s national database to identify Veterans whose sexual orientation is recorded as lesbian, gay, bisexual or queer (LGBQ+) and gender identity as transgender woman (TGW)/man (TGM), non-binary or another gender (except cisgender) [transgender or gender diverse (TGD)] as of April 2024. Birth sex male LGBQ+ and TGD Veterans of both birth sexes were included in the cohort, stratified by age, race/ethnicity and HIV status. Within these cohorts we quantified receipt of JYNNEOS vaccine in the VHA starting 2022.

Results

Among the 42,434 males who identify as LGBQ+, 4759 (11.2%) had received at least one dose of the JYNNEOS vaccine; of these, 74% completed the series. There were large variabilities in vaccine uptake among LGBQ+ males by age: the 19-29 cohort had the lowest uptake at 5.2% and lowest series completion rate at 58.1% while the 50-59 age group had the highest uptake at 15.6% (Figure 1). Among racial groups, Asian LGBQ+ males had the highest uptake at 19.3%, and Whites had the lowest uptake at 9.4% (Figure 2). Black and Hispanic LGBQ+ males had better than average uptake at 14.7% and 15.6% respectively. Among 111,338 Veterans who identify as TGD, only 138 (1.2%) had received at least one dose by the end of observation period. Among these, TGW had the highest number of persons vaccinated (n=73) but non-binary Veterans had highest rate at 2.6% (Figure 3). Those with HIV were much more likely to have received at least one dose of the vaccine compared to those without (LGBQ+ males 25.5% vs. 7.6%; TGD 15.1% vs. 1%) (Figure 4).

Conclusion

TGD Veterans were much less likely to have received Mpox vaccination in the VHA compared to LGBQ+ males, with HIV status being the strongest predictor of vaccination in both groups. While the overall rates of Mpox vaccination appear lower in the VHA compared to general population, we did not see racial disparities that have been reported in Blacks but observed age related differences.

Disclosures

All Authors: No reported disclosures
P-77. Ceftaroline versus Daptomycin as Definitive Treatment for Methicillin-Resistant Staphylococcus aureus Bone and Joint Infections
Authors: Goodman Reid , Ney Katheryn , Liang Stephen Y , Marschall Jonas
Published: January 2025

Background

There are no comparative effectiveness studies of ceftaroline versus other antibiotics for MRSA bone and joint infections (BJI). We retrospectively compared the clinical outcomes of patients with MRSA BJI initially treated with vancomycin and then transitioned to either ceftaroline (VtoC) or daptomycin (VtoD).

Methods

This retrospective nested case-control study analyzed data from a large Midwest academic center collected from 2018-2022. Patients with MRSA BJI whose definitive treatment was ceftaroline were compared in a 1:2 ratio to patients whose definitive treatment was daptomycin. The primary outcome was clinical success after initial treatment course (i.e., at 6 weeks) defined by a composite endpoint which included resolution of signs and symptoms and no repeat surgery or re-admission for treatment of the index BJI.

Results

We identified 36 patients to be included in this case-control study, with 12 VtoC cases and 24 VtoD cases. The demographic make-up was similar, as was the frequency of comorbidities (including Charlson score). Of the VtoC patients, 42% had implant-related infection vs. 17% of the VtoD group (p=0.1). A larger proportion of VtoC patients had systemic MRSA infection as documented by positive blood cultures (58% vs 38%; p=0.2). More VtoC cases were direct ICU admits (50% vs 13%; p=0.04), required intubation (58% vs 17%; p=0.02), or were admitted to the ICU at any point during their stay (67% vs 29%; p=0.07). Transition away from vancomycin occurred at 14.3 vs 10.6 days (p=0.6). There was only a single clinical success in the 12 VtoC patients (8%) vs. 7/24 (29%) in the VtoD group (p=0.2), with the majority of cases being failures (30.5%), all-cause deaths (30.5%), or lost to follow-up (16.7%). Follow-up was 103 vs 123 days (p=0.8) in the two groups.

Conclusion

In this comparison of ceftaroline to daptomycin for MRSA BJI we found ceftaroline recipients to have more severe illness (as suggested by need for ICU care) and experience very little clinical success. We suspect that there is selection bias in that more severely ill cases anticipated to have poor outcomes were more likely to be transitioned to ceftaroline. Our next steps are to include more data and conduct a propensity score analysis to better understand what factors are associated with transition to ceftaroline.

Disclosures

All Authors: No reported disclosures
P-78. Observational Comparison of In-Person vs. Remote Care for Bone and Joint Infections
Authors: Gupta Nupur , Mehta Steinke Seema , Nanjappa Sowmya , D’Angelo Nicholas , Kowdley Devan , Wong Victoria R , Abdel-Massih Rima , Mellors John W , Shah Neel
Published: January 2025

Background

Telemedicine can overcome barriers to accessing subspecialty expertise including for infectious disease (ID). A common need for ID expertise is bone and joint infections (BJI), which are associated with substantial morbidity and mortality. Access to BJI expertise in underserved locations could be increased through ID telemedicine (Tele-ID). Here, we compare patients, and outcomes of Tele-ID vs in-person ID care of BJI.Table 1:Characteristics of the Study Population

Methods

We conducted a retrospective study of BJI patients who received Tele-ID (live audio-video) care at hospital #1 vs. in-person ID care at hospital #2 between 2015-2019. Both hospitals are affiliated with a larger academic institution and have care provided by the same ID physicians. Demographic data, comorbidities, diagnostic and microbiological data, treatment, and outcomes were assessed.Table 2:Primary Outcomes of the Study Population

Results

Of the first 100 patients, half received Tele-ID care at hospital #1 and the other half received in-person ID care at hospital #2. Both groups had similar patient characteristics (Table 1), except for higher frequency of same site infection at hospital #2 (68 vs 26%). Patients cared for via Tele-ID were more often transferred to an alternative tertiary-care facility (30% vs. 0%) for surgical specialty services not available at hospital #1 (Table 2). For Tele-ID patients transferred vs in-person care, LOS was longer and discharge to home occurred less often compared with those not transferred. Readmission for the same infection within 30 days and mortality were not different (Table 2). The most common BJI managed by Tele-ID was diabetic foot osteomyelitis without any hardware, whereas joint infections with hardware were most commonly seen by in-person ID (Figure 1). Amongst patients with OR procedures, most OR cultures were negative, with Staphylococcus aureus being isolated most frequently at both hospitals (Figure 2).Figure 1:Type of Infection by Hospital

Conclusion

This initial observational study suggests that clinical outcomes are similar for patients with BJI cared for by in-person vs. Tele-ID, although hospital transfer for surgical interventions was more common at the Tele-ID site. Further comparison in a larger number of patients at each hospital is ongoing. This preliminary experience suggests that Tele-ID could provide appropriate care for BJI where in-person ID expertise is not available.Figure 2:OR Culture Organism(s) by Hospital

Disclosures

Seema Mehta Steinke, MD, MS, Pearl Diagnostics: Advisor/Consultant Rima Abdel-Massih, MD, Infectious Disease Connect: CEO & co-founder|Infectious Disease Connect: Ownership Interest John W. Mellors, MD, Infectious Disease (ID) Connect, Inc.: Share Options
P-82. Doxycycline versus other oral antibiotics for the treatment of gram-positive bone and joint infections
Authors: Corbino Joseph , Martin Tyler , Patel Manish , Andruski Rebecca , Kandiah Sheena , Schechter Marcos , Aldred Bruce
Published: January 2025

Background

The OVIVA trial demonstrated oral agents with high bioavailability after one week of IV treatment is non-inferior in treatment of bone and joint infections (BJI) compared to continued IV therapy. Oral therapy significantly reduced rates of IV catheter complications and hospital length of stay. Certain highly bioavailable oral options with coverage for gram-positive organisms were well studied in this phase III trial, such as linezolid (LZD) and trimethoprim/sulfamethoxazole (TMP/SMX), with doxycycline representing a small proportion. LZD and TMP/SMX exceeded their respective Clinical and Laboratory Standards Institute (CLSI) breakpoints and MIC90 values in the bone. Doxycycline achieves concentrations of 3 mcg/mL in the bone but may not reach upper concentrations of susceptibility per the CLSI breakpoint (≤ 4 mcg/mL). LZD and TMP/SMX penetrate the bone well, but adverse effects may make prolonged therapy difficult to tolerate compared to doxycycline.

Methods

A retrospective chart review was conducted of individuals ≥ 18 years prescribed doxycycline or either LZD or TMP/SMX for the treatment of a presumed or confirmed gram-positive BJI within the Grady Health System between January 1, 2021, and June 30, 2022. Individuals were included if they were referred to an ID provider within our Transitions of Care clinic and received oral antibiotics for ≥1 week on discharge. The composite primary outcome was suggested or performed amputation, OR debridement, all-cause mortality, or re-initiation of antibiotics. Secondary outcomes include rate of primary therapy completion and incidence of adverse effects.

Results

77 patients met inclusion for the study, doxycycline (n=33) and LZD or TMP/SMX (n=44). There was no significant difference in the primary outcome at 9 months between either group (10 vs 12, p=0.77). Loss to follow-up drove incompletion rates of primary antibiotic therapy in both groups. Laboratory adverse effects were more common in the LZD or TMP/SMX group compared to doxycycline.

Conclusion

Doxycycline may be associated with a favorable adverse effect profile compared to LZD or TMP/SMX. The efficacy of doxycycline compared to LZD or TMP/SMX should be considered exploratory with larger studies conducted to highlight its potential place in practice.

Disclosures

All Authors: No reported disclosures
P-86. Utility of Metagenomic Next-Generation Sequencing in Detecting Pathogens Causing Orthopedic and ENT Infections
Authors: McConnell Alia , Hussain Anila , Edmonston Tina B , Ianosi-Irimie Monica , Nikolic Dejan
Published: January 2025

Background

Traditional methods such as gram stain and cultures are recommended to identify pathogens from patient specimens. Metagenomic Next-Generation Sequencing (mNGS) is a new attractive technology to detect occult infections, that does not provide susceptibilities, with not well-established utility. We compared results of mNGS tests performed at Microgen Reference lab to those of traditional culturing on patient outcomes.

Methods

This retrospective study includes all patients from Aug 2022 to Dec 2023 whose biopsy samples were submitted for both traditional culturing and mNGS diagnostic tests. Clinical and lab data were extracted from the electronic medical record. Patient outcomes when utilizing traditional versus mNGS diagnostic methods were compared.

Results

53 orthopedics and ENT cases were studied. 31/41 (75.6%) orthopedic cases (spine, hips, and synovial fluid) had concordant results, with 19 (46.3%) concordant negative cases and 12 (29.3%) concordant positive cases showing similar organism(s). Of the discordant cases, 12.2% (5/41) mNGS results were accurate, and 9.75% (4/41) culture results were accurate. One specimen (2.44%) showed contamination with both methods. Of 12 ENT cases, overall concordance of accurate results was only 50%, 1 negative case and 5 cases showing the same organism(s) with both methods. 16.7% (2/12) the culture results were accurate while mNGS results were incorrect, and 4/12 (33.3%) specimens showed contamination by both methods.

Conclusion

Utilizing mNGS versus traditional methods did not result in any changes in patient management like empirical and targeted antibiotic regimen or in hospitalization outcomes including duration of therapy or length of stay. The accuracy of the testing is equivalent, while mNGS is much more expensive and not readily available in clinical labs, resulting in longer TAT (6 days vs. cultures 3 days). The quality of results is mainly affected by the quality of the specimen (33% contamination for ENT specimens). These data ultimately guided the stewardship discussions about utilizing mNGS at CUHC to discourage mNGS testing for ENT sources unless the collection method is improved and reserve the utilization of mNGS for challenging orthopedic cases.

Disclosures

All Authors: No reported disclosures
P-106. Preliminary Results of the

C

omparing

O

ral versus

P

arenteral

A

ntimicrobial

T

herapy (COPAT) Clinical Trial
Authors: Juskowich Joy J , Thompson Jesse M , Guilfoose John A , Lastinger Allison , Stanley Jonathan E , Smith Connie L , Arcega Victor A , Bage Seyoum , Sarwari Arif R
Published: January 2025

Background

Early intravenous (IV) to oral (PO) antibiotic transition for serious infections such as bacteremia, endocarditis, and bone/joint infections is noninferior to continued IV antibiotics. Our experience shows that Complex Outpatient Antimicrobial Therapy with PO antimicrobials (COpAT) is not only clinically effective but much safer. However, COpAT programs are not yet widely incorporated into clinical practice. Comparing Oral vs. Parenteral Antimicrobial Therapy (COPAT) Trial was designed to demonstrate improved safety with equivalent effectiveness of early IV to PO antibiotic transition across almost all infectious diseases. We hypothesized that, without compromising clinical outcomes, adverse events (readmissions, antibiotic toxicities, and line issues) will be significantly lower in patients discharged with PO antibiotics.

Methods

COPAT Trial is an ongoing open-label, pragmatic, randomized controlled trial at five Infectious Disease faculty staffed hospitals in one health system. A total 135 hospitalized patients otherwise being discharged with two or more weeks of IV antibiotics are randomized 2:1 to early PO (Experimental) vs. continued IV (Control) antibiotics. Two primary outcomes, assessed at 12 weeks, are efficacy equivalence and Experimental group safety superiority. From Aug 4, 2023 through Apr 30, 2024, 73 (Experimental 48, Control 25) active patients were enrolled and 64 (Experimental 42, Control 22) completed the trial.

Results

Demographics and infection type were similarly distributed between both groups with a predominance of bone/joint followed by endovascular infections (Table 1). While total antibiotic durations were comparable, Experimental group received disproportionately more PO antibiotics (87 vs. 37%, p< 0.05) (Figure 1). Both groups had a strong preference for PO antibiotics, and all patients felt their infection had been successfully treated (Table 2). Experimental group had a significantly lower total adverse event rate (2.8 vs. 7.2%, p< 0.05) (Table 3). All patients achieved clinical cure at 12 weeks.

Conclusion

Early IV to PO transition significantly improves antimicrobial treatment safety without compromising effectiveness across many serious infectious diseases. Patients report a strong preference for PO antibiotics.

Disclosures

All Authors: No reported disclosures
P-115. Lessons from Establishing a Vaccine Trial Clinic: Insights from the University of Louisville's Center of Excellence for Research in Infectious Diseases
Authors: Shafique Nouman , Shahnawaz Waqas , Balcom Dawn
Published: January 2025

Background

The COVID-19 pandemic spurred an urgent need for swift vaccine development to combat the disease. This study focuses on outlining the implementation approach for the Phase 3 clinical trial of the Ad26.COV2.S vaccine. The University of Louisville's Division of Infectious Diseases, known as the Center of Excellence for Research in Infectious Diseases (CERID), was contacted by Janssen representatives in July 2020 to conduct the trial.Figure 1.The structure of the Center of Excellence for Research in Infectious Diseases (CERID).

Methods

The CERID site was fully activated in November 2020, and the enrollment period spanned 16 working days, from November 21 to December 11, 2020. The study employed a randomized, double-blind, placebo-controlled design. Various organizational units within CERID, including community outreach, implementation, quality assurance, and laboratory, collaborated to develop standard operating protocols for communication and execution. These steps included community outreach, trainings, and the development of case report forms.Figure 2.Data collected at Screening and Day 1 participant visits.

Results

During the enrollment period, 64 participants were seen, with 62 enrolled in the trial. The self-sufficient organizational infrastructure of CERID was pivotal in facilitating the successful implementation of the Phase 3 clinical trial. Quality metrics were developed to minimize systematic errors and ensure accurate reporting of results. The Division of Infectious Diseases Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory provided essential support for COVID-19 diagnosis, sample processing, and shipping.Figure 3.Workflow in laboratory. Gold top humoral blood collection tube, PAXgene RNA blood sequencing tube, NP specimen tube, and saliva samples were delivered to the laboratory. Specimens processed per laboratory manual and stored in the -80°C freezer until shipping to the central laboratory.

Conclusion

The seamless execution of the Phase 3 clinical trial at CERID highlights the effectiveness of a multidisciplinary research coordinating center. The collaborative efforts of various units within CERID, along with proactive measures such as pre-labeling specimen tubes and addressing participant concerns directly, contributed to the trial's success. The described methods and approach can be adapted for use in diverse clinical and laboratory research settings, showcasing resilience and adaptability in the face of pandemic challenges

Disclosures

All Authors: No reported disclosures