bluuebunny/crossref_metadata_2025_split huggingface dataset:
1856. Barriers to Improving Outcomes among People Experiencing Homelessness and People Who Inject Drugs Hospitalized for Complicated Infections
Authors: Parke Dana M , Kenney Rachel M , Bogojevich John , El-Khoury Caren , Joshi Seema , Brar Simran , MacDonald Lynsey , Salib Christina , MacDonald Nancy , Veve Michael , Suleyman Geehan 
Published: November 2023

Abstract

Background
People experiencing homelessness (PEH) and people who inject drugs (PWID) experience health disparities and worse outcomes. Challenges include suboptimal medication use, loss to follow-up, and non-compliance due to social determinant of health (SDOH) barriers, including lack of stable housing and transportation, limited financial resources, substance use, and addiction.

Methods
This quality improvement project aimed to address SDOH barriers among hospitalized PEH and/or PWID requiring ≥ 2 weeks of antibiotics to improve antibiotic compliance and outcomes in Detroit from 6/2022-4/2023. Interventions included antibiotic education, addiction medicine and pharmacy discharge medication cost inquiry consults when indicated, ensuring oral antibiotics were in hand at discharge, strengthening discharge planning between inpatient and ambulatory case managers (ACM), and referrals to community-based organizations to address SDOH needs.

Results
34 patients were included (8 PEH, 11 PWID, 15 both); 3 who died in the hospital were excluded. Multiple individual and structural barriers and challenges to improving adherence and outcomes were identified (Table 1). Loss to follow-up was a significant challenge among this cohort, primarily due to patients self-discharging (29%) and being unreachable (52%). 10 (37%) patients were offered SDOH services (Table 2). Patients also had significant behavioral health/substance use disorder needs and utilized healthcare at a very high rate, with 29% having an ED revisit and 44% being readmitted within 30 days after discharge. Several structural and SDOH barriers existed, including limited staff capacity and limited placement options after discharge, resulting in suboptimal treatment delivery.

Conclusion
Addressing SDOH barriers for PEH and PWID is challenging but vital to improving outcomes. Qualitative research should be conducted to understand these barriers. Having an interdisciplinary team comprising of infectious diseases, pharmacy, addiction medicine, case management and population health is critical to address patient needs holistically. Strengthening internal processes and building additional community-based partnerships will be essential to better meet patient needs after discharge.

Disclosures
Michael Veve, PharmD, MPH, National Institutes of Health: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support
1865. Refractory Nontuberculous Mycobacterial Pulmonary Disease: Natural History and Burden of Illness in Patients from the US Bronchiectasis and NTM Research Registry (BRR)
Authors: Aksamit Timothy R , Choate Radmila , Mannino David M , Brunton Amanda E , Wang Ping , Hassan Mariam 
Published: November 2023

Abstract

Background
Nontuberculous mycobacterial pulmonary disease (NTMPD) is a chronic lung infection that is challenging to treat, especially refractory NTMPD. Data are limited on the natural history, risk profile, and burden of refractory NTMPD. The objective of this study was to evaluate the burden of illness (BOI) among patients with NTMPD who later develop refractory NTMPD vs those who do not.

Methods
This was a retrospective analysis using BRR data. Patients treated for NTMPD were included and stratified as refractory (received oral clofazimine/bedaquiline or inhaled amikacin/ALIS, or remained sputum culture positive despite ≥ 6 months of treatment) or nonrefractory. Modified bronchiectasis severity index (mBSI) at baseline visit and BOI including comorbid conditions and surgeries at the treatment visit were compared by cross-sectional analysis between the two groups. Longitudinal analysis of BOI focused on exacerbations and hospitalizations in the refractory group at their pre-refractory visit and refractory visit (first visit meeting the refractory definition).

Results
A total of 1,064 patients treated for NTMPD were included: 462 (43.4%) refractory and 602 (56.6%) nonrefractory. During the baseline period, the refractory group had more severe bronchiectasis (Table 1, mBSI, mean [SD], 7.3 [3.4] vs 6.7 [3.4]). At the time of treatment, bronchiectasis was more common in the refractory than nonrefractory (96.2% vs 89.7%) group, as were hemoptysis (26.6% vs 16.3%) and GERD (50.5% vs 39.9%). Except BMI, there were no statistically significant differences between the pre-refractory and nonrefractory treatment visits (Table 2). In the refractory group, exacerbations and hospitalizations remained high from the pre-refractory to refractory visit (45.6% vs 39.4% and 13.3% vs 12.8%, respectively). Oxygen and bronchial hygiene use increased from the pre-refractory to the refractory visit (5.2% vs 9.3% and 54.5% vs 61.7%, respectively) consistent with increased management of respiratory conditions when not responding to treatment (Table 2).

Conclusion
Refractory NTMPD imposes a high disease burden on patients in the BRR. This high burden was present at pre-refractory visits and through the development of refractory status.

Disclosures
Timothy R. Aksamit, MD, AstraZeneca: Advisor/Consultant|Baxter International, Hill-Rom: Advisor/Consultant|Insmed Incorporated: Advisor/Consultant|Johnson & Johnson: Advisor/Consultant|Redhill Biopharma: Advisor/Consultant|RespirTech: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant|Zambon: Advisor/Consultant David M. Mannino, MD, AstraZeneca: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|Up to Date: Advisor/Consultant Ping Wang, PhD, Insmed Incorporated: Salary|Insmed Incorporated: Stocks/Bonds Mariam Hassan, PhD, B. Pharm, Insmed Incorporated: Salary|Insmed Incorporated: Stocks/Bonds
1871. Lessons Learned from IGRA Test Practices in a Tertiary Hospital
Authors: Daas Farah , Ruiz-Gaviria Rafael , Thummar Bhakti , Khan Naveera , Ramdeen Sheena 
Published: November 2023

Abstract

Background
Interferon Gamma Release Assay (IGRA) is frequently ordered in hospitalized patients for latent tuberculosis (TB) screening. Health care workers must be cautioned that acute and critical illness exert a significant effect on IGRA performance, so delaying screening to the outpatient setting is preferred if feasible. When active TB is suspected, IGRA can aid in risk stratification, particularly in areas with low prevalence of TB, but should not be used to confirm or rule out active TB infection. False negative IGRA results in active TB are estimated to be up to 20%. Current guidelines from the Centers for Disease Control and Prevention, the Infectious Diseases Society of America and the American Thoracic Society suggest that IGRA cannot distinguish active from latent TB and recommend prompt microbiological testing when active TB is suspected.

Methods
We conducted a retrospective chart review on hospitalized patients older than 18 years in a tertiary academic center who had an IGRA test done from January 1, 2021, to December 31, 2021. We randomly selected 78 from the 417 identified patients for collection of encounter level data.

Results
IGRA test indications were screening for latent TB in 53.8%, to investigate active pulmonary TB in 30.8%, and for other reasons in 6.4%. IGRA tests had no clear indication in 9% of cases. IGRA test results were 84.6% negative; 10.3% positive; and 5.1% indeterminate. After a negative IGRA, microbiological testing was ordered in 12%, with 1 positive test confirming active TB.
Active TB was suspected in 30.8% of our cohort. Microbiologic testing was done in 41.6% of these patients. In most of the patients with microbiological testing, ordering was delayed until a positive IGRA was available with an average delay of 2.4 days.

Conclusion
Collection of sputum for microbiological testing should not be delayed until IGRA test results are available, and negative results should be scrutinized when suspicion for active TB is high. Caution must be practiced in interpreting IGRA results, and we should not solely rely on IGRA in decision-making regarding isolation, treatment, or further testing. Education of health care staff may be required regarding the indications and timing of IGRA testing.

Disclosures
All Authors: No reported disclosures
1878. Short message service (SMS) alert and reschedule an appointment to shorten physician delay of TB treatment: A quasi-experimental study
Authors: Angkasekwinai Nasikarn , Guayboon Theerajet , Ngamskulrungroj Popchai 
Published: November 2023

Abstract

Background
Tuberculosis (TB) continues to pose a major health threat during the ongoing coronavirus diseases 2019 (COVID-19) pandemic in Thailand. Delays of TB treatment either due to patients or healthcare system resulted in an unfavorable outcome. There is limited study using information technology to diminish physician delay of TB treatment.

Methods
This was a quasi-experimental study conducted from June 2019 to February 2022 at Siriraj Hospital to assess the impact of using the short message service (SMS) alerts and rescheduling an appointment to shorten the physician delay in starting TB treatment. Patients were eligible if they were ≥18 years and having a positive TB test results by either one of the following: acid-fast bacilli (AFB) smear, polymerase chain reaction (PCR) for TB, or mycobacterial culture reporting M. tuberculosis complex. The primary outcome was the duration from reporting the first positive TB test to the treatment initiation.

Service flow and interventions, including SMS notification and rescheduling service.
Figure 2
Screening, exclusion and analysis populations in pre-implementation or routine care and post-implementation of SMS service.

Results
Among 364 patients, 206 patients and 158 patients were included in the no SMS and the SMS groups, respectively. The SMS group had a significantly higher proportion of being treated in the OPD setting (94.3% vs 67%, p&lt; 0.001), treated by staff (42% vs. 23.5%, p&lt; 0.001), and treated by pulmonologists (54.4% vs. 36.2%, p=0.004) than the no SMS group. Patients in the SMS group had a longer median time from the first visit to treatment (29 days [14.0, 57.8] vs.12 days [5.0, 47.5], p&lt; 0.001), specimen collection to treatment (15.5 days [7.0, 31.8] vs. 6.5 days [2.0, 22.8], p&lt; 0.001), and reporting results to treatment (9 days [5.0, 16.0] vs. 3.5 days [1.0, 12.0], p&lt; 0.001) than the no SMS group. However, among TB patients being treated in the OPD setting and having a culture as the first positive result, those in the SMS group had a significantly shorter median time from specimen collection to treatment than the no SMS group (36 days [29.0, 51.0] vs. 60 days [39.0, 101.0], p=0.018). The median time from reporting the results to treatment was also shorter in the SMS group (9 days [6.0, 30.0] vs. 25 days [6.3, 81.0], p=0.172) but there was no statistically significant difference.

Conclusion
SMS notification could reduce healthcare system delays in the initiation of TB treatment among TB patients who have positive mycobacterial cultures, but negative AFB smear and PCR-TB.

Disclosures
All Authors: No reported disclosures
1879. Paradoxical Reaction in Lymph Node Tuberculosis among HIV-negative Patients: Incidence, Predictive Factors, and Clinical Outcomes
Authors: Gupta Ankesh , Kumar Santosh , Jorwal Pankaj , Singh Binit K 
Published: November 2023

Abstract

Background
The aim of this study is to evaluate the occurrence of paradoxical reactions (PRs), cytokine levels and outcome in HIV-negative lymphnode tuberculosis (TB) patients.

Methods
This is a prospective observational study conducted at the All-India Institute of Medical Sciences in New Delhi, India from July 2019 to June 2021. 144 subjects with confirmed or probable lymph node TB, excluding MDR TB, were recruited. Baseline characteristics, clinical presentation, imaging, laboratory parameters, and TB diagnostic modalities were gathered. Patients were followed up to evaluate the occurrence of PRs, and cytokines IL2, IL6, IL18, and TNF alpha were analyzed using the sandwich ELISA principle at baseline and after PR development.

Workflow of the study.

Results
Total 144 subjects with confirmed tuberculosis were recruited. PRs developed in 5.5% of patients, with fever (58.74%) and weight loss (44.06%) being the predominant systemic symptoms. The median time for PR development was 37 days, with pain and swelling being the most common presentation (62.5%). Among the baseline cytokines, IL6 was the most elevated (20.83%), with IL2, IL18, and TNF alpha being elevated in 8.3%, 0.69%, and 1.38% of the subjects, respectively. On multivariate analysis, baseline elevation of interleukin 2 was statistically significant and predicted PRs. IL2 and IL6 were significantly elevated during the occurrence of PRs, while IL18 and TNF alpha were not. Most patients (75%) improved on NSAIDs, with a median symptom resolution duration of 30 days.
Comparison of patient parameters at baseline and after the development of paradoxical reactions.
Comparison of cytokine levels at baseline and after paradoxical reactions.

Paradoxical reaction features, tuberculosis diagnostic modalities and treatment modalities of paradoxical reaction.

Conclusion
Our study found that baseline elevation of IL-2 and worsening adenopathy and weight loss during treatment are potential predictors for paradoxical reaction in lymph-node tuberculosis. However, it is important to validate these findings through larger prospective studies.

Disclosures
All Authors: No reported disclosures
1896. Analysis of Virulence Factors and Antibiotic Resistance Genes in Mycobacterium abscessus Prophage Sequences genomes and Relationships with Clinical Patient Prognoses
Authors: Sichun Luan 
Published: November 2023

Abstract

Background
M. abscessus is known for its multiple resistance to antibiotics, and diseases caused by M. abscessus have limited methods to treat with. Little is known for prophages carried by M. abscessus, nor their role played in diseases.

Methods
Strains identified as M. abscessus from patients from December 2017 to August 2021 were included. Prophages, virulence factors and antibiotic resistance genes in genomes were analyzed. The correlation between prophages, virulence factors and antibiotic resistance genes contained, and clinical patient prognoses were analyzed. The sequence similarity between prophages and known phages were analyzed.

Results
A total of 145 prophage sequences were detected in 56 M. abscessus strains. The average number of intact prophages was 0.7 ± 0.6. The average number and gene proportion of virulence factors and drug resistance genes in prophages were higher than those in known mycobacteriophages. Differences of average prophage carried, virulence factors and drug-resistant genes, and their proportions between different prognoses were not statistically significant, except for virulence factors. The average similarity of prophage sequences in single patient was 99.86%; which was significantly higher of the average matching rate of 89.27% in different patients and the total similarity of 78.28% between prophages and known phages. No clear positive correlation between tested common virulence factors or virulence factors and clinical patient prognoses was observed.

Conclusion
M. abscessus commonly carries prophages, and they have higher contents of virulence factors and drug resistance genes than known phages. The prophage detected in patients with good prognosis carried more virulence factors, and its meaning was unclear. The composition of the prophage sequences in the strains isolated from the same patient is stable, with occasional base mutation or deletion. Prophages carried in strains of different patients were highly diverse, and shared low similarity with known mycobacterium phages.

Disclosures
All Authors: No reported disclosures
1900. Disseminated and Extrapulmonary Nontuberculous Mycobacteria (NTM): Disease Management, Adverse Treatment Reactions, and Outcomes
Authors: Wang Heather , Sobhanie Mohammad Mahdee , Nichols Courtney 
Published: November 2023

Abstract

Background
Guidelines for the management of pulmonary nontuberculous mycobacterial (NTM) infections are well defined; however, similar guidelines for the treatment of disseminated or extrapulmonary NTM infections are lacking. This study aimed to describe our institutional experience in the treatment of disseminated and extrapulmonary NTM infections, and to better characterize the disease course, management, and outcomes in this patient population.

Methods
This single-center retrospective study was conducted at The Ohio State University Wexner Medical Center in patients who were diagnosed with disseminated or extrapulmonary NTM infection from November 1, 2011 to November 1, 2021. Only index cases were included in patients with a documented culture positive for an NTM, and patients with a positive pulmonary culture were only included if they had a documented extra-pulmonary site as well.

Results
58 patients met inclusion criteria and 54 were started on antibiotic therapy. 41.4% (N=24) and 31.0% (N=18) were started on two and three antibiotics as initial therapy, respectively. 32 (59.3%) patients required changes to their initial regimen, of which 31.3% (N=10) were changed due to intolerance or adverse event. The mean time to onset of antibiotic intolerance or adverse drug events was 129.4 days (6-404 days). 67.2% (N=39) of patients had documented resolution of their infections, with 7 patients currently on antibiotic therapy at the end of the study period (38.9%).
The most common antibiotic classes used included macrolides (64.8%), carbapenems (35.2%), ethambutol (25.9%), and aminoglycosides (22.2%). The antibiotic classes with most frequent intolerances were linezolid (42%), aminoglycosides (31.6%) and clarithromycin (21.0%) at a mean duration of 39.3, 72.2, and 32 days, respectively.
Table 1. NTM infection characteristics, including infection site, species breakdown, and disease outcome.
Table 2. NTM treatment regimen details and reasons for changing and/or not completing planned antibiotic regimen for all study patients.

Table 3. Breakdown of antibiotic classes used in initial treatment regimens for dNTM-infected patients, along with antibiotics that caused patient intolerances. For each antibiotic class that caused intolerance, average time to develop intolerance listed.

Conclusion
Treatment of disseminated and extrapulmonary NTM infections typically requires a complicated treatment course due to prolonged durations of multiple antibiotics, patient intolerances to antibiotic classes, and difficulty with determining appropriate end of therapy timing. Additional studies are needed to better outline the ideal antibiotic regimens and duration for disseminated and extrapulmonary NTM infections.

Disclosures
All Authors: No reported disclosures
2129. Antimicrobial Activity of Cefepime in Combination with Taniborbactam Against Resistant Clinical Isolates from the United States 2018-2021
Authors: Hackel Meredith , Wise Mark G , Sahm Daniel F 
Published: November 2023

Abstract

Background
Taniborbactam is a novel, investigational broad-spectrum β-lactamase inhibitor with direct inhibitory activity against both serine- and metallo-β-lactamases. Taniborbactam restores the activity of cefepime (FEP) against many difficult to treat organisms, including cephalosporin- and carbapenem-resistant Enterobacterales (EB) and Pseudomonas aeruginosa (PA). The activity of cefepime-taniborbactam (FTB) and comparator agents was evaluated against nonsusceptible (NS)/resistant (R) clinical isolates of EB and PA from the United States (US) collected in global surveillance.

Methods
MICs of FTB (taniborbactam fixed at 4 µg/mL) and comparators were determined using the CLSI reference method against EB (n=4,220) and PA (n=1,222) from the US collected in 2018-2021. NS/R phenotypes were based on 2023 CLSI breakpoints (EUCAST breakpoint for meropenem-vaborbactam [MEV] against PA). Multidrug R (MDR) was defined as R to ≥1 agent from ≥3 drug classes.

Results
Overall, 13.1% and 10.3% of EB isolates were NS to FEP and piperacillin-tazobactam (TZP), respectively (Table). FTB had potent activity against all EB (MIC50/90, 0.03/0.12 µg/mL; 99.9% inhibited at ≤16 µg/mL). FTB maintained activity against NS/R subsets of EB (MIC90 range, 1 to 8 µg/mL; 90.0% to 99.3% inhibited at ≤16 µg/mL) including MDR isolates (MIC90, 2 µg/mL; 98.4% inhibited at ≤16 µg/mL). FTB was the most active tested agent against PA overall (MIC50/90, 2/8 µg/mL; 97.7% inhibited at ≤16 µg/mL). Among meropenem (MEM)-NS isolates, 91.2% were inhibited by FTB at ≤16 µg/mL compared to 76.6% susceptible to ceftolozane-tazobactam (CT). FTB at ≤16 µg/mL inhibited 74.2% of CT NS isolates of PA whereas 47.2% of isolates of this phenotype were susceptible to ceftazidime-avibactam (CZA). Against MDR PA (13.4% of all PA), FTB (MIC50/90, 8/32 µg/mL) inhibited 85.4% of isolates at ≤16 µg/mL compared to 59.1% that were susceptible to CT.

Conclusion
Cefepime-taniborbactam had potent in vitro activity against recent EB and PA from the US, including MDR isolates and isolates NS to FEP, MEM, TZP, CZA, CT, and/or MEV. These data support continued development of cefepime-taniborbactam as a potential treatment option for challenging infections due to resistant Gram-negative pathogens.

Disclosures
Meredith Hackel, PhD, Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Mark G Wise, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation