bluuebunny/crossref_metadata_2025_split huggingface dataset:
1883. Features and Outcomes of Tuberculosis in Documented versus Undocumented Migrants in Israel
Authors: Zohar Iris , Pomeranz Adam , Harari Orna Schwartz , Ben-David Debby , Maor Yasmin 
Published: November 2023

Abstract

Background
In countries with low tuberculosis (TB) incidence, most TB cases are observed in foreign-born individuals, including permanent immigrants, and undocumented migrants. There is limited information regarding the differences within these groups. In Israel, where TB prevalence is &lt; 2 cases/100,000 persons, 85% of TB cases occur in foreign-born people. We examined risk factors, clinical course, and outcomes between documented and undocumented immigrants hospitalized with active TB.

Methods
A retrospective analysis of medical records from foreign-born active TB patients admitted to a 700-bed hospital in the center of Israel between January 1st, 2019, to March 31st, 2023. We included patients who initiated TB treatment during hospitalization and were discharged by April 2023. Undocumented migrants were defined as non-Israeli citizens without medical insurance. We summarized their clinical characteristics, course, and outcomes.

Results
48 patients were included, 21 (43.8%) were undocumented migrants. Undocumented migrants were younger (mean age 40.9 vs. 53.0 years, P&lt; 0.001) and predominantly arrived from Africa (95.2% vs. 29.6%, P&lt; 0.001). The prevalence of HIV was similar between both groups. Presenting symptoms, duration of symptoms before admission, rates of bilateral and cavitary pulmonary disease, and extrapulmonary disease were comparable. Multi-drug resistant TB was rare (0% vs. 11.5%, P=0.242). Among patients with positive sputum smears and follow-up, undocumented migrants experienced a longer time to achieve negative sputum cultures (76.0 days vs. 36.8 days, P=0.004), and hospitalizations lasting over 30 days were also more common among undocumented migrants (71.4% vs. 40.7%, P=0.045). Multivariate analysis identified undocumented migrant status, thrombocytosis, and bilateral and cavitary pulmonary disease as risk factors for prolonged hospitalization.

Conclusion
Although the clinical features of TB were similar between documented and undocumented migrants, the response to treatment was slower, and hospital stays were longer among undocumented migrants. This may be due to undocumented migrants presenting with more advanced disease or lack of suitable conditions for isolation and treatment at home.

Disclosures
Yasmin Maor, MD, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Honoraria|Gilead: Honoraria|GSK: Honoraria|kamada: Honoraria|Medison: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria
1898. Optimizing selection of latent TB management strategies among immigrants from high TB burden settings to the United States
Authors: Sinha Pranay , Jacobson Karen R , Horsburgh C Robert , Linas Benjamin P , Acuña-Villaorduña Carlos 
Published: November 2023

Abstract

Background
Treatment for latent tuberculosis infection (LTBI) with rifampin and isoniazid is very effective but carries significant hepatotoxicity risks, increasing with age. Further, since the risk of progression to tuberculosis (TB) disease declines with increasing time from exposure, the risk is highest among recent immigrants. Current guidelines may therefore promote overtreatment of LTBI, particular in older immunocompetent individuals who immigrated many years previously.

Methods
Using observed data from the Boston Medical Center/Boston Public Health Commission TB clinic and best literature estimates, we designed a microsimulation model to simulate TB progression among immunocompetent adult immigrants from high TB burden countries without abnormal radiography, alcohol or tobacco use, or recent TB contacts over a 30-year horizon (Table 1). We assumed that the simulated individuals were exposed to TB immediately prior to immigration. TB progression rates are based on years since exposure (Table 1). We evaluated three strategies: 1. No treatment 2. Rifampin and 3. Isoniazid for new 35 years-old and 65 years-old immigrants and for 35 and 65 years-old immigrants who had immigrated 25 years previously. We simulated hepatotoxicity using published estimates (Table 2). The model calculates costs and outcomes (TB cases and disability-adjusted life years) associated with each strategy. We used deterministic and probabilistic sensitivity analyses to test robustness of our results.

Results
Among new immigrants both 35 and 65 years-old, rifampin provides better outcomes at lower cost than both the isoniazid and no treatment strategies (Table 3). Among those who immigrated 25 years ago, Rifampin remains the preferred strategy in 75% of simulations for 35 years-old individuals and no treatment was preferred in 100% of iterations for 65 years-old patients. For those unable to receive rifampin due to drug interactions, no treatment became the preferred strategy for a broader range of individuals (Figures 1a and 1b).

Conclusion
Age and time since immigration must be considered to determine whether LTBI therapy is indicated in immunocompetent immigrants from high TB burden countries. Our results could help clinicians optimize strategies for LTBI treatment and minimize harm.

Disclosures
All Authors: No reported disclosures
1901. High Prevalence of Latent Tuberculosis Infection in a Malaysian Prison
Authors: Zhang Lu , Shenoi Sheela , Kamarulzaman Adeeba , Dhaliwal Sangeeth , Ahmad Ahsan , Altice Frederick 
Published: November 2023

Abstract

Background
Given the rising tuberculosis (TB) incidence and mortality, strengthening the identification and treatment of those with latent tuberculosis infection (LTBI) is urgently needed. Prisons are a TB hotspot but there is a paucity of data on LTBI in prisons. This study characterized LTBI in the largest prison in Malaysia.

Methods
From 22nd October 2019 to 19th January 2023, adults newly admitted (&lt; 2 days) to the Kajang men’s prison without current active TB (excluded by negative culture, Acid-Fast Bacillus smear, or GeneXpert results) or a history of active TB in the past 2 years, were invited to participate. Enrollees underwent tuberculin skin tests (TST), chest X-ray, and blood tests for HIV, hepatitis C (HCV), hepatitis B, and c-reactive protein (CRP). Sociodemographic variables and drug use history were collected by questionnaires. LTBI was defined as TST size ≥ 5mm for people living with HIV and ≥ 10mm for people living without HIV, without evidence of active TB. Multivariable logistic regression was performed to identify independent correlates of LTBI by stepwise backward regression with inclusive factors from univariate analysis (p&lt; 0.1). Multicollinearity was checked by the variance inflation factor (VIF).

Results
We enrolled 601 eligible people deprived of liberty, with a median age of 42 (IQR 36-50), 8.8% living with HIV, 43.4% with HCV infection. The prevalence of LTBI was 68.2% (95%CI: 64.4%-71.8%). The independent risk factors for LTBI overall (Table 1) included opioid use disorder, history of homelessness, and HCV. Marijuana use was associated with decreased risk of LTBI among all cases and among people with HIV. For people without HIV, HCV and CRP≥ 5mg/ml were independent risk factors for LTBI, while methamphetamine use was associated with a reduced risk of LTBI.

Conclusion
The prevalence of LTBI in a Malaysian prison was high, necessitating the implementation of TB preventive therapy. The high prevalence of HCV may increase the risk of hepatotoxicity during LTBI treatment. Further data is needed on the risks of TB preventive therapy among people deprived of liberty.

Disclosures
All Authors: No reported disclosures
2902. Dalbavancin Use in Bone and Joint Infections
Authors: Sanikommu Srivani , Alderson Liam P , Bailey Brett , Stambough Jeffrey , Stronach Benjamin , Mears Simon , Dare Ryan K 
Published: November 2023

Abstract

Background
Dalbavancin (DAL) is currently FDA-approved to treat acute bacterial skin and soft tissue infections. Use of DAL for off-label indications have been reported in difficult-to-treat infections, including osteomyelitis and prosthetic joint infections. Once weekly DAL dosing is an attractive alternative to daily intravenous (IV) infusions decreasing risks of prolonged home IV therapy. However, effectiveness for treatment of bone and joint infections is unknown

Methods
This single-center, retrospective, observational study included adult patients who received at least one dose of DAL from 09/2019-03/2023 for bone and joint infections. Patient demographics including state and national area of deprivation index (ADI) data, underlying infection, dalbavancin indication, surgical and medical treatments, and clinical outcomes were obtained. Risk factor analyses were performed for 1-year infection recurrence using Stata 15.0 statistical software.

Results
Fifty-eight patients were treated with DAL with a mean age was 44.3 years, with males comprising 71% with a mean BMI of 28.6. This vulnerable patient population had an Arkansas ADI decile of 6.1 and a national ADI percentile of 81.2. Osteomyelitis (81%), prosthetic joint infections (PJIs) (10.3%,), and native joint infections (8.6%) were included. Twenty-five (43.1%) patients had infected hardware involved. The majority (86.2%) of patients underwent surgical debridement and 17 (29%) required hardware removal, leaving 8 (13.8%) with retained hardware. Staphylococcus aureus was the most common organism identified with 39.7% and 31.0% MRSA and MSSA respectively. The most common DAL indication was IV drug use (43%). Recurrence of infection occurred in 8 patients (13.7%) within 90 days and 10 patients (17.2%) at one year. Hardware retention was noted to be a significant risk factor for recurrence (p=0.024), and hardware removal decreased risk of recurrence (p= 0.026). There was no recurrence in PJIs and there were no deaths noted.

Conclusion
Our evidence suggests that DAL is an effective treatment option for bone and joint infections with debridement and hardware removal. Hardware retention increased risk for 1-year recurrence. Further evaluation with prospective, randomized controlled trials is needed.

Disclosures
All Authors: No reported disclosures
2128. In Vitro Activity of Ceftibuten-Avibactam and Comparator Agents Against Resistant Enterobacterales from UTIs Collected Globally as Part of the ATLAS Surveillance Program, 2022
Authors: Hackel Meredith , Stone Gregory , Sahm Daniel F 
Published: November 2023

Abstract

Background
Increasing resistance among agents commonly prescribed to treat urinary tract infections (UTIs) indicate that new orally bioavailable agents are needed. Ceftibuten (CTB) is an orally administered third-generation cephalosporin and is in early clinical development being combined with an oral prodrug of avibactam (AVI). AVI is a non-β-lactam inhibitor of Ambler class A β-lactamases, including ESBLs and KPCs, class C (AmpC) β-lactamases, and some class D (OXA-48) β-lactamases. Ceftibuten-avibactam prodrug (CBA) is in early clinical development as a potential oral treatment for complicated urinary tract infections. This study evaluated the in vitro activity of CBA and oral comparators against Enterobacterales from UTIs with drug-resistant phenotypes collected globally as part of the 2022 Antimicrobial Testing Leadership and Surveillance (ATLAS) program.

Methods
4,265 non-duplicate clinical isolates from UTIs were collected in 2022 in 55 countries. Susceptibility testing with CBA tested at a fixed concentration of 4 µg/mL AVI and comparators was performed by CLSI broth microdilution and interpreted using CLSI 2023 breakpoints. Nonsusceptible (NS)/resistant (R) phenotypes were based on 2023 CLSI breakpoints. MDR was defined as R to ≥1 agent from ≥3 drug classes.

Results
CBA was the most active compound tested against all Enterobacterales, with the MIC90 value decreasing from 32 µg/mL to 0.12 µg/mL. A total of 96% of all isolates were inhibited at a CBA MIC of ≤1 µg/mL. Percent susceptible of oral comparators ranged from 63.4% to 76.8%. CBA maintained activity against NS/R subsets of Enterobacterales (MIC90 range, 0.25 to 4 µg/mL; 85.0% to 93.2% inhibited at ≤1 µg/mL), including MDR isolates (MIC90, &gt;64 µg/mL; 81.7% inhibited at ≤1 µg/mL).

Conclusion
Ceftibuten-avibactam demonstrated potent in vitro activity against multidrug-resistant Enterobacterales collected globally. Ceftibuten -avibactam prodrug could be an effective oral therapy for difficult-to-treat infections caused by multidrug-resistant Enterobacterales.

Disclosures
Meredith Hackel, PhD, Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Gregory Stone, PhD, Pfizer: Stocks/Bonds Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation
2135. Epetraborole in vitro Activity Against Mycobacterium avium complex Recent Clinical Isolates from Japan
Authors: White Tiffany Keepers , Aono Akio , Igarashi Yuriko , Chikamatsu Kinuyo , Takaki Akiko , Mitarai Satoshi 
Published: November 2023

Abstract

Background
Epetraborole (EBO) is a boron-containing, oral inhibitor of bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis. EBO demonstrates potent activity against nontuberculous mycobacteria and is currently under clinical development for treatment of treatment-refractory Mycobacterium avium complex (MAC) lung disease. The objective of this study was to evaluate the in vitro activity of EBO against recent MAC isolates from Japan.

Methods
Minimal inhibitory concentration (MIC) values for EBO, amikacin (AMK), clarithromycin (CLR), rifabutin (RFB), and ethambutol (EMB) were determined using broth microdilution assays according to Clinical and Laboratory Standards Institute M24-A3 guideline (2018) against 110 MAC clinical isolates collected from Japanese patients in 2020. MAC isolates were of respiratory origin and included 55 M. avium and 55 M. intracellulare isolates.

Results
EBO (MIC) values ranged from 0.25 - 16 µg/mL and the EBO MIC50 and MIC90 were 2 and 4 µg/mL, respectively (Table 1). The CLR MIC range was 0.125 - &gt; 32 µg/mL and included 4 CLR-resistant isolates (MIC ≥ 32 µg/mL). CLR MIC50 and MIC90 were 1 and 4 µg/mL, respectively. All isolates were susceptible to AMK and had an MIC range of 2 - 32 µg/mL; the MIC50 and MIC90 were 8 and 16 µg/mL, respectively. The EMB MIC range was 2 - &gt; 32 µg/mL; the MIC50 and MIC90 were 4 and 16 µg/mL, and the RFB MIC range was ≤0.03 - 2 µg/mL and MIC50 and MIC90 were 0.06 and 0.25 µg/mL. EBO maintained activity with MIC values of 0.25 - 2 µg/mL against the 4 CLR-resistant isolates.
Epetraborole and comparator antimicrobial minimum inhibitory concentration values against 110 recent Mycobacterium avium complex clinical isolates from Japan
MIC=minimal inhibitory concentration; MIC50=minimal inhibitory concentration for 50% of isolates tested; MIC90=minimal inhibitory concentration for 90% of isolates tested.

Conclusion
EBO demonstrated potent in vitro activity against 110 recent MAC isolates collected from Japanese patients. Furthermore, EBO demonstrated in vitro activity against CLR-resistant MAC isolates suggesting that CLR-resistance does not impact EBO activity. These data are similar to results obtained against U.S. isolates and support the continued clinical evaluation of the use of EBO in the treatment of MAC lung disease in Japan.

Disclosures
Tiffany Keepers White, PhD, AN2 Therapeutics: Employee|AN2 Therapeutics: Stocks/Bonds Satoshi Mitarai, MD, PhD, AN2 Therapeutics, Inc.: Grant/Research Support
2141. Preclinical Evaluation of PA-001: A Novel, Potential Macrocyclic Peptide-Based Treatment for COVID-19 Which Binds to the S2 Subunit of SARS-CoV-2 Spike Protein
Authors: Kawamura Tatsuro , Ohuchi Masaki , Nagasawa Takayuki , Ohashi Hirofumi , Iwata-Yoshikawa Naoko , Shiwa-Sudo Nozomi , Sakai Yusuke , Matsui Katsuma , Matsumoto Masatoshi , Kurasaki Haruaki , Nagatomo Kazutaka , Ito Shoko , Kawamura Naoki , Masuya Keiichi , Nagata Noriyo , Watashi Koichi , Suzuki Tadaki , Kitamura Hidetomo , Murakami Masato 
Published: November 2023

Abstract

Background
Despite the approval of a few COVID-19 drugs, various mutations of SARS-CoV-2 continue to emerge and pose as a threat to the efficacy of COVID-19 treatments. To address the unmet clinical need for broad-spectrum treatments, we identified and performed preclinical evaluation of PA-001, a macrocyclic peptide that targets the highly conserved S2 subunit (S2) of the spike protein of SARS-CoV-2, as a potential therapeutic agent with a new mechanism of action.

Methods
A diverse macrocyclic peptide library was constructed and screened for S2 binders employing PeptiDream’s proprietary technology, Peptide Discovery Platform System (PDPS). In vitro antiviral activity was evaluated in VeroE6/TMPRSS2 cells infected with SARS-CoV-2 using RT-qPCR. In vivo efficacy was evaluated in a lethal BALB/c mouse model infected with a mouse-adapted SARS-CoV-2 strain, QHmusX, where PA-001, the remdesivir metabolite GS-441524, alone or in combination, or molnupiravir were therapeutically administered for 3 consecutive days started at 1-day post-inoculation (Fig. 1).Figure 1.Schematic design of the in vivo efficacy study

Results
PA-001 was identified as a S2 binding peptide through PDPS. PA-001 showed in vitro antiviral activity against wild-type and variant strains of SARS-CoV-2 including Omicron (IC50: 1.7 – 9.6 nM). Therapeutic administration of PA-001 completely rescued mice from SARS-CoV-2-caused death at the anticipated clinical dose, while 80% of molnupiravir-administered mice died (Fig. 2A). In addition, treatment with PA-001 alone significantly suppressed body weight loss (Fig. 2B), decreased lung weight-to-body weight ratio (an indicator of lung inflammation), and reduced inflammatory cytokines secretion including IL-6 in lungs, and these effects were enhanced when combined with GS-441524.Figure 2.Survival rate and body weight change of SARS-CoV-2-infected mice

Conclusion
The S2-targeting peptide PA-001 showed potent in vitro antiviral activity and in vivo preclinical therapeutic efficacy. These data support the possibility that PA-001 could become a novel drug with a unique mechanism of action for the treatment of COVID-19. Currently, IND submission for PA-001 is in preparation to initiate clinical trials.

Disclosures
All Authors: No reported disclosures
2145. Antagonistic Activity of Lacticseibacillus rhamnosus R3 Against Carbapenem-Resistant Acinetobacter baumannii Strain: A Promising Therapeutic Alternative
Authors: Rodriguez Cecilia , Ramlaoui Dema , Georgeos Nardin , Gasca Briea , Leal Camila , Salzameda Nicholas , Bonomo Robert A , Raya Raul , Ramirez Maria Soledad 
Published: November 2023

Abstract

Background
Acinetobacter baumannii (AB) is a recognized nosocomial pathogen of critical importance Most circulating AB strains are carbapenem-resistant (CRAB), which severely complicates therapeutics with available antibiotics. Probiotic lactic acid bacteria constitute a promising therapeutic alternative. Previously, we determined that Lacticaseibacillus rhamnosus R3 (LR-R3) exerts a strong inhibitory capacity on the model strain A118 (susceptible to antibiotics). In this analysis, the antimicrobial activity of LR-R3 against type CRAB hypervirulent strain AB5075 was evaluated.
Figure 1
A) Transwell migration assay. AB5075 viability after 24h exposure to LR-R3 CFCM. B) CFCM activity obtained from 96h culture of LR-R3 on CRAB strains.

Methods
The inhibitory activity of cell pellet and its cell-free supernatants (CFCM) were determined, respectively, by the soft-agar overlay method, CFCM activity, and transwell migration assay. Also, killing assays and scanning microscopy imaging were performed under co-culture conditions. Lastly, AB5075 transcriptional response when exposed to LR-R3 was assessed by RT-qPCR.

Results
The lactic acid bacteria LR-R3 demonstrated a strong inhibitory capacity on AB5075 strain (inhibition halo diameter, DHI &gt;20 mm), with loss of cell viability at 4h of co-culture conditions. The CFCM of LR-R3 also showed similar antimicrobial activity on AB5075 (Fig 1A) and against others CRAB strains (Fig 1B), suggesting that the inhibitory effect observed is due to the presence of a compound or metabolite produced and secreted by the lactobacillus.
Microscopy images showed increase formation of outer membrane vesicles (OMVs) and the presence of nanotubes. In addition, significant changes in the expression levels of the studied genes were observed in AB5075 in co-culture with LR-R3: increase in the expression of genes involved in biofilm (csuAB, csuB, ompA); and decrease in the expression of genes involved in the synthesis and utilization of iron (bauA, exbD, bfnA, basE, pirA), and genes related to fatty acid and lipid metabolism (paaA, paaB).

Conclusion
The results obtained allowed the identification of Lcb. rhamnosus R3 as a probiotic strain with antagonistic activity on the nosocomial pathogen A. baumannii. In addition, it was shown that LR-R3 alters iron and fatty acid metabolism, by virtue of this interaction. This work constitutes the basis for future studies necessary to elucidate the mechanism involved.

Disclosures
Robert A. bonomo, MD, Entasis, Merck, VenatoRx, Wockhardt: Grant/Research Support
2195. Impact of Optimizing Urine Culture Susceptibility Reports on Prescribing of Antimicrobials in Outpatients at the Atlanta VA Health Care System (AVAHCS)
Authors: Gale Christopher , Goolsby Tiffany , Webster Andrew S 
Published: November 2023

Abstract

Background
To encourage appropriate prescribing in uncomplicated urinary tract infections (UTIs), the AVAHCS optimized urine susceptibility reports by adding comments guiding selection of narrow-spectrum beta-lactams for Enterococcus spp and certain Enterobacterales (E. coli, K. pneumoniae, Proteus spp) and hiding the susceptibility of levofloxacin for Enterococcus spp. The purpose of this study is to determine the impact of these changes on antibiotic selection in outpatients.

Methods
This study was a retrospective chart review of patients with positive urine cultures for the target organisms from March - December 2019 and March - December 2022. Patients were included if they had urine cultures that resulted with one of the target organisms and received UTI treatment. Those excluded had positive blood cultures or were hospitalized at the time of sample collection, had a previous urine culture or received treatment for UTI within 30 days, had a urological procedure in the preceding 12 months, or had a polymicrobial culture result. The primary outcome was the percent change in the use of quinolones before and after implementation. Secondary outcomes included the percent change in the use of aminopenicillins and cephalosporins for Enterococcus spp and Enterobacterales, respectively.

Results
For Enterococcus spp, there was a 29.2% decrease in the selection of quinolones as definitive therapy. There was a 37.1% increase in the use of aminopenicillins as definitive therapy. For Enterobacterales, there was a 15% decrease in the selection of quinolones as definitive therapy. There was a 13.3% increase in the use of first-generation cephalosporins as definitive therapy.

Conclusion
For Enterococcus spp UTI, following suppression of levofloxacin from the C&S reports and addition of provider comments, quinolones were less likely to be prescribed and aminopenicillins were more likely to be prescribed. In Enterobacterales UTI, following addition of prescriber comments, quinolones were less likely to be prescribed and first-generation cephalosporins were more likely to be prescribed, though the increase was less pronounced than was seen in the Enterococcus spp group. These results suggest the combination of susceptibility suppression and comments was more impactful than a comment alone.

Disclosures
All Authors: No reported disclosures