bluuebunny/crossref_metadata_2025_split huggingface dataset:
2900. Clinical Utility of Repeat Magnetic Resonance Imaging Studies Among Children with Acute Hematogenous Osteomyelitis
Authors: Thorne Abby , Moss Angela , Sanders Julia S , Stein Jill , Searns Justin B 
Published: November 2023

Abstract

Background
Magnetic resonance imaging (MRI) is the diagnostic study of choice for children with acute hematogenous osteomyelitis (AHO). However, there is limited guidance for whether repeat MRIs are clinically impactful for children with AHO who fail to improve after initial treatment. This study aimed to determine whether repeat MRIs changed clinical management among children with AHO.

Methods
Children admitted to a quaternary care pediatric hospital with a discharge diagnosis of osteomyelitis were identified during a 9-year period. Patients with chronic symptoms, non-hematogenous infections, or significant contributing comorbidities were excluded. Medical records were retrospectively reviewed for all MRIs performed 3 weeks prior to admission to 24 months after discharge. An MRI was considered clinically impactful if it identified a new infectious process (e.g., abscess not seen on initial MRI) or if it resulted in surgical intervention within 24 hours. Categorical variables were compared using Fisher’s Exact or chi-square tests and continuous with Wilcoxon Rank-Sum tests.

Results
Among 239 included patients, 41 (17%) had more than 1 MRI performed during clinical care for their AHO. Twenty-nine repeat MRIs occurred during initial hospitalization and 27 during outpatient follow up. Children who underwent repeat inpatient MRIs had longer hospitalizations (9 vs 5 days, P&lt; 0.01) and higher C-reactive protein levels (20 vs 7 mg/dL, P&lt; 0.01), and were more likely to be critically ill (20% vs 6%, P=0.02) or to experience a therapeutic failure (20% vs 3%, P&lt; 0.01). Among repeat inpatient MRIs, 19 (66%) were clinically impactful; 9 (31%) led to repeat surgical procedures and 13 (45%) identified new diagnoses. Repeat outpatient MRIs were more likely to be performed in children with vertebral AHO or multifocal infections (P=0.02). Among repeat outpatient MRIs, 7 (25%) were clinically impactful. Six (22%) led to repeat operative procedures and 3 (11%) identified new diagnoses.

Conclusion
When used judiciously among ill children with complicated AHO, repeat MRI can be clinically impactful in both the inpatient and outpatient setting. Prospective studies are needed to better define which children with AHO benefit from repeat MRI.

Disclosures
Julia S. Sanders, MD, OrthoPediatrics Corp: Advisor/Consultant
1890. Evaluating the effect of respiratory isolation for TB on patient- and public health-important outcomes- a systematic review
Authors: Pearl Abarna , Biewer Amanda M , Delrooz Naveed , Subramanian Advaith , Miller Sarah E , Mukasa Leonard , Young Laura R , Mase Sundari R , Munsiff Sonal , Nardell Edward , Nathavitharana Ruvandhi 
Published: November 2023

Abstract

Background
The duration of respiratory isolation for infectious tuberculosis (TB) is based on limited data and expert opinion. Yet the impact of isolation on persons with TB and public health programs is significant. This systematic review synthesized evidence on public health and patient-important outcomes of respiratory isolation for TB to inform revised National TB Controllers Association guidelines.

Methods
We searched PubMed, EMBASE, CINAHL, Web of Science, Cochrane Central and WHO-Global Index Medicus using terms for TB and respiratory isolation (Figure). Eight reviewers screened abstracts, full-texts, and extracted data in pairs. Inclusion criteria were data on effects of respiratory isolation compared to no isolation or masking. Studies were stratified by outcomes: TB infection or TB disease in contacts, mortality, hospitalization duration, patient and health system costs, and impact on mental health or stigma. A convergent mixed methods approach was used to integrate quantitative and qualitative findings and assess limitations.

Results
After screening 3640 publications, 17 studies: randomized controlled trial (1), quasi-experimental (1), cohort (1), modelling (3), mixed-methods studies (3), and qualitative (8), were included. The trial (conducted in the 1950s) suggested treatment in isolation in a sanatorium versus at home did not affect TB infection (22% versus 23%) or disease incidence (11% versus 10.5%) in contacts (Table 1). Modelling studies suggest isolation may reduce transmission, including drug-resistant TB, but highlighted isolation is rarely implemented without other interventions, including treatment or masking. Many studies described adverse impacts of isolation on employment, education, food/housing security, and mental health due to transmission fears, stigma and social isolation (Tables 2 & 3). Impacts were compounded in marginalized groups such as indigenous and incarcerated persons.

Conclusion
Data to support current isolation practices, particularly once effective treatment is started, to reduce TB transmission in communities are limited. Public health guidance should consider the negative impacts on persons with TB against the potential for transmission reduction to facilitate evidence-based decisions about respiratory isolation.

Disclosures
All Authors: No reported disclosures
1891. Descriptive Epidemiology of African-American Patients with Tuberculosis in in Detroit
Authors: Sandhu Avnish , Pollock Erin , Smith Shona , Sunstrum James , Kissner Dana 
Published: November 2023

Abstract

Background
Knowing local risk factors for tuberculosis (TB) facilitates identification of individuals with latent or active TB. The purpose of this study is to describe the epidemiology of TB among patients seen in the Detroit Health Department. We will refer to our study population as Detroit TB cases.

Methods
A retrospective descriptive study was conducted in collaboration with the Michigan Department of Health and Human Services. TB data submitted to MDHHS from Detroit between January 2017 and December 2022 was evaluated. Information on demographics, genotype clusters, and clinical / lifestyle risk factors was collected

Results
One-hundred forty-one TB cases were verified in Detroit during the study period and will be referred to as the study population. See Table 1 for baseline demographics. Sixty percent (85) of cases were males. Fifty-eight % (81) were Black / African American (B/AA). Sixty-two % (87) of cases were born in the U.S. Of persons with positive cultures for TB, 45% (37) were in a genotype cluster. Please see figure 1 for example of genotype cluster. The major clinical risk factors were diabetes mellitus in 31% (43) of cases, followed by incomplete treatment of latent TB infection (LTBI) in 11% (16). Major life-style risk factors included any substance use in 24% (34), non-injecting drug use in 18% (26), and excess alcohol use in 13% (18) of cases.

Conclusion
This study highlights epidemiologic differences between individuals with TB in Detroit and the US. Almost 60% of the 141 Detroit TB cases were B/AA. Nationally, 10% of non-US-born individuals and 30% of US-born ones were B/AA in 2022. More than 60% of the Detroit cases were US-born. This is in stark contrast to the U.S., where 37% of cases in 2022 were US-born. A significant number of Detroiters belonged to a genotype cluster, indicating continued transmission of TB. Alcohol and drug use were major lifestyle risk factors, suggesting increased contact in shared venues contributing to transmission of TB. Knowing these local risk factors for TB should lead to earlier detection and treatment of TB and LTBI and eliminate opportunities for transmission.

Disclosures
All Authors: No reported disclosures
2901. Associations between climate and diabetic foot infection microbiology: a systematic review and meta-analysis
Authors: Rabin Benjamin , Lockwood Sophie M , Martinson Ellen , Urquhart-Foster Kyra , Bhanushali Priyanka , Raymond Julia , McAloon Meg , Dunbar Jillian , Otchere Baffour , White Mia S , Schechter Marcos 
Published: November 2023

Abstract

Background
Diabetic foot infections (DFIs) are the leading cause of preventable limb loss globally. The International Working Group on Diabetic Foot Infection guidelines advise an empiric antibiotic regimen choice for DFI partly based on climate: gram-negative and P. aeruginosa active antibiotics are recommended for people residing in subtropical and tropical climates with moderate and severe DFIs. However, there is limited data supporting this recommendation. Our systematic review and meta-analysis aimed to understand the prevalence of gram-negative and P. aeruginosa DFIs across solar climate zones (temperate, subtropical, and tropical).

Methods
We searched PubMed, Embase, AIM, IMSEAR, IMEMR, LILACS, and WPRIM for studies published in any language between 2010-2020 reporting ≥5 unique patients with a DFI (Figure 1). Two reviewers independently assessed studies for eligibility, and we used double data entry. The senior author resolved disagreements. We assigned climate zone based on study center location and built Forest plots to depict the proportion of patients with (1) ≥1 gram-negative bacteria and (2) with P. aeruginosa­ in foot soft tissue and/or bone cultures. We reported common and random effects models.

Results
293 studies out of 4101 studies met our inclusion criteria. Of these, 53 studies representing 4,970 patients reported the proportion of patients with gram negative infections, and 270 studies representing 36,026 patients reported the proportion with P. aeruginosa. A random effects model found the proportion of patients with gram negative infection varied by climate zone: 40% (95% confidence interval 33% – 54%) in temperate regions; 58% (95% CI 51% – 65%) in sub-tropical regions; and 67% (95% CI 49% – 61%) in tropical regions (Figure 2). The proportion of DFI with P. aeruginosa was 14% (95% CI 12% - 17%) in temperate areas; 15% (95% CI 13% - 17%) in subtropical regions; and 16% (95% CI 14 – 17%) in tropical regions (Figure 3).Figure 2:Meta analysis of the proportion of gram negative DFI infection by solar climateFigure 3:Meta analysis of the proportion of Pseudomonas aeruginosa DFI infection by solar climate

Conclusion
Our meta-analysis suggests that gram-negative infections occur at higher proportions in tropical and sub-tropical areas compared to temperate regions. Future studies should aim to elucidate the interactions between other risk factors for gram-negative and/or P. aeruginosa DFIs (e.g., antibiotic exposure, infection severity) and climate.

Disclosures
All Authors: No reported disclosures
1893. Mathematical modeling the impact of the age-dependent latent tuberculosis treatment on active tuberculosis in South Korea
Authors: Seong Hye , Lee Yunjeong , Seo Jiyeon , Hyun Hakjun , Yoon Jin Gu , Nham Eliel , Noh Ji Yun , Cheong Hee Jin , Kim Woo Joo , Lee Jeehyun , Song Joon Young 
Published: November 2023

Abstract

Background
As most of the tuberculosis (TB) cases occur from latent TB (LTBI) reactivation, effective therapeutic interventions for LTBI are crucial to national TB control. Age is one of the important factors affecting LTBI treatment and management. This study assessed the impact of the age-dependent intervention on the treatment rate, the probability of treatment success for LTBI, and the overall incidence of active TB cases in South Korea.

Methods
We developed an age-structured dynamic compartmental model to describe the person-to-person transmission of TB focused on latent TB in South Korea. We calibrated the model to an annual number of active TB cases from 2011 to 2018 reported by Korea Disease Control and Prevention Agency. The model estimated averted active TB cases for 30 years, and sensitivity analysis was performed by changing the treatment coverage and success rates for LTBI, stratified by age groups.
The mathematical model for tuberculosis transmission in South Korea

Results
In the model simulation, the number of new active TB cases gradually decreased in 19-34 and 35-64 age groups but gradually increased in the elderly. Among three age groups, the intervention of LTBI in 35-64 age group markedly reduced total active TB cases by reducing both acute infection and reactivation from LTBI cases. When the LTBI treatment rate increased by 4-times in 35-64 age group, the 32,785 active TB cases were averted, while in 19-34 and ≥65 age groups, 11,597 and 5,678 cases were averted, respectively. When changing the probability of treatment success, similar results were shown also. The 19-35 age group was most affected by the change in the LTBI treatment success rate compared to other age groups. Assuming the probability of treatment success approached 100%, 1,290, 3,208 and 822 active TB cases were averted in 19-34, 35-64 and ≥65 age groups, respectively.
The incidence rates are plotted for all ages (top left), 19-34 (top right), 35-64 (bottom left), and 65+ (bottom right) age groups.
The incidence rates are plotted for all ages (top left), 19-34 (top right), 35-64 (bottom left), and 65+ (bottom right) age groups.
Active TB cases in 2048 year according to changes of LTBI treatment rate for each age group

Conclusion
The model simulation suggested that changes in the treatment coverage and success rates of LTBI may have different effects by the age group. LTBI control measures affected the 35-64 year age group more significantly than the other age groups.

Disclosures
Hee Jin Cheong, M.D.,Ph.D., Sequiris: Advisor/Consultant
1895. Omadacycline for the Treatment of Non-Pulmonary Mycobacterial Infections: a Single-Center Retrospective Review
Authors: Shen Edmund , Albin John , Hysell Kristen , Hurtado Rocio M 
Published: November 2023

Abstract

Background
Infections due to rapidly growing mycobacteria (RGM) such as M. abscessus, M. chelonae and M. fortuitum typically require long and toxic regimens, with complex resistance patterns and limited oral options further producing suboptimal efficacy. Since its approval in 2018, however, the tetracycline derivative omadacycline has established new options in antibiotic management. We report here clinical experience with the use of omadacycline for non-pulmonary RGM infections within the Mass General Brigham (MGB) system.

Methods
The study was approved by the MGB Institutional Review Board (2022P001578). Electronic ambulatory notes in the MGB Research Patient Data Registry (RPDR) from 2012-present were filtered by the term “omadacycline,” and manual chart review was conducted for individuals treated for non-pulmonary RGM infections.
Flow diagram of chart review procedure for identification of non-pulmonary RGM patients

Results
Chart review revealed 25 patients with omadacycline-treated non-pulmonary RGM infections. The median age was 50, 52% female and 48% male. In total, 16 were infected with M. abscessus (64%), 8 with M. chelonae (32%), and 1 with M. immunogenum. 18 cases were skin and soft tissue infections (72%), 4 cases were bone and joint infections (16%), and 3 cases were disseminated infections (12%). Most patients (88%) received omadacycline as part of a step-down or a salvage regimen; 3 (12%) received omadacycline in initial treatment. 17 patients (68%) had completed regimens as of April 2023. Among these cases, the median duration of omadacycline use was 5 months (range=0.25-16). Patients within this cohort generally experienced clinical improvement. Adverse effects–most commonly nausea–were noted in 6 (24%) cases. No patients were discontinued due to the severity of these effects, though one regimen was temporarily paused due to hyperlipasemia.
Non-pulmonary RGM patient cohort demographics, Mycobacterial species, and site of infection.

Conclusion
Omadacycline is an increasingly common component of the treatment of RGM infections, with use in multidrug regimens appearing generally effective and well-tolerated. Limitations of this study include its retrospective nature and evaluation within a single health system. To our knowledge, however, this is the largest series on omadacycline in RGM infections reported to-date. This analysis provides support for the further evaluation of omadacycline outcomes among patients with RGM infections.

Disclosures
All Authors: No reported disclosures
2107. Anti-Biofilm Potential of Virulence Factor EsxB of Staphylococcus aureus against its own Sensitive Strain: Molecular Evidences
Authors: Ashraf Faryal , Maharjan Rukesh , tul-Wahab Atia , Choudhary Iqbal 
Published: November 2023

Abstract

Background
Staphylococcus aureus express different proteins that modulate intracellular bacterial survival and increase antimicrobial resistance with higher mortality rate. The EsxA and EsxB, substrates of the ESAT-6 like secretion system (Ess) are important during intracellular S.aureus infection. The genes EsxA and EsxB are present in close proximity with 6 other genes, including EsaA, EssA, EsaB, EssB, EssC, and EsaC.

Methods
EsxB virulence gene from vancomycin resistant S. aureus was cloned and transformed into expression cell line E.coli BL21(DE3) cells under IPTG induction. The expressed proteins were purified using affinity and size exclusion chromatography. Purity and protein structures were checked by using NMR spectroscopy and circular dichroism. Further, purified proteins were evaluated for it's hemolytic and antibiofilm property against S. Aureus (ATCC 6538).

Results
he purified EsaB protein showed well spread spectra of 1H- NMR spectrum, however, the 15N, 1H-HSQC spectrum showed overlapped peaks or contours in the region of 6.5-10 ppm indicating the absence of well folded 3D conformation in solution state. Circular dichroism showed the presence of beta sheets in structure of EsxB virulence factor. EsxB protein showed antibiofilm activity against S.aureus (ATCC 6538) when treated exogenously. It also showed non hemolytic activity indicating it's non-cytotoxic nature.

Conclusion
This study explains the evidence that bacterial virulent protein EsxB possess antibiofilm activity against its own sensitive strain.

Disclosures
All Authors: No reported disclosures
2903. Early Experience With Omadacycline For The Treatment Of Diabetic Foot Infections
Authors: Crotty Matthew P , Akins Ronda L , Dominguez Edward A , Alexander Julie , Alexander Nebu 
Published: November 2023

Abstract

Background
Diabetic foot infections (DFI) are often polymicrobial and increasingly caused by resistant pathogens. Progression of resistance requires utilization of broad-spectrum agents, further exacerbating the problem and resulting in collateral damage. Frequently used regimens are often complicated by adverse effects of acute kidney injury (AKI) and Clostridioides difficile infection (CDI). The unique spectrum of activity of omadacycline (OMC), availability both intravenously (IV) and orally, along with its safety profile may provide an optimal treatment for DFIs.

Methods
This is a prospective, open-label, two-center study (NCT04714411) to assess the safety of OMC use in the treatment of hospitalized subjects with moderate to severe DFI with or without acute osteomyelitis (AOM, defined as initial diagnosis) who are at high risk for development of CDI, AKI, and/or resistant pathogens. Adults (≥18 years) hospitalized with DFI were eligible. All subjects received OMC 200 mg IV once on day 1 followed by either 100 mg IV or 300 mg by mouth once daily for 14-21 days without AOM or 42 days with AOM. Clinical success was defined as infection resolution or sufficient clinical improvement requiring no other antibiotics.

Results
11 patients were enrolled and received OMC for DFI treatment (Table 1). Most patients had AOM (8/11, 72.7%) and systemic inflammatory response syndrome criteria were met in 5 of 11 (45.5%). All patients were converted to oral therapy with median time of 4 days (IQR, 2-5 days). Median hospital stay was 11 days (IQR, 9-15). 8 patients completed treatment with all achieving clinical success at end of therapy (EOT; Figure 1). At test-of-cure (TOC; EOT + 30 days), 6/8 (75%) patients had clinical success. Among two patients not achieving clinical success, one received additional antibiotic therapy during a subsequent hospitalization and the other had growth of Proteus mirabilis from local culture. At long-term follow-up (LFU; EOT + 60 days), 6/8 (75%) achieved clinical success. No instances of AKI or CDI were observed. Adverse effects were reported by two patients (nausea and burning sensation at injection site).

Conclusion
Early experience with OMC suggests it may be a potential treatment for some patient with DFI including AOM. Continued investigation for this indication is warranted.

Disclosures
Matthew P. Crotty, PharmD, BCIDP, Paratek Pharmaceuticals Inc.: Grant/Research Support Ronda L. Akins, PharmD, Paratek Pharmaceuticals, Inc.: Grant/Research Support
2118. Comparative Analysis of Cefiderocol Mono- and Combination Therapy for Multi-Drug Resistant Gram-negative Infections
Authors: Ghali Amer El , Kunz-coyne Ashlan , Lucas Kristen , Tieman Molly , Purdy Andrew , Iturralde Gabriela , Garcia Esther , Holger Dana , Lau Suet-Ping , Xhemali Xhilda , Veve Michael P , Rybak Michael J 
Published: November 2023

Abstract

Background
Multi-drug resistant gram-negative infections are a growing concern, necessitating the development of novel treatments. Cefiderocol (CFDC) is a new siderophore cephalosporin that targets the iron transport mechanism used by many gram-negative pathogens. We aimed to compare the clinical outcomes of CFDC monotherapy and combination therapy in various infection types.

Methods
We performed a retrospective cohort analysis at 5 academic medical centers from May 2022 to April 2023. Patients were included if they were ≥18 years old and received CFDC for ≥48 hours, excluding subsequent courses not separated by ≥90 days. The primary objective was composite clinical success (30-day survival, absence of 30-day infection recurrence and resolution of signs and symptoms), with secondary objectives including individual components of clinical success, on-treatment resistance, 30-day readmission, and adverse reactions. Descriptive statistics and logistic regression were used.

Results
We analyzed 70 patients, with 35 in each treatment group. The cohort was predominantly male (64.3%), had a mean age of 55.5 years (17.6), and 67% were admitted to the Intensive Care Unit. The mean (SD) APACHE II scores were 12.8 (7.5) for monotherapy and 14.9 (6.7) for combination therapy (p=0.22), while the mean (SD) Charlson comorbidity scores were 5.0 (3.6) and 4.5 (3.5) for the respective groups (p=0.61). The most common infection source was respiratory tract (54.3%), with Pseudomonas aeruginosa (55.7%) and Acinetobacter baumannii (25.7%) as the most frequently isolated pathogens. The median (IQR) CFDC mean inhibitory concentration (MIC) was 0.5 µg/mL (0.25-1.0). The 30-day mortality rates for the monotherapy and combination groups were 20% and 28.6%, respectively. There was no significant difference in composite clinical success between the groups (p=0.59).

Conclusion
Our preliminary data suggest that there is no difference in clinical success between CFDC monotherapy and combination therapy with another antibiotic. Further studies are needed to confirm these findings and evaluate the optimal use of CFDC in a variety of clinical settings.

Disclosures
Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Merck, Paratek, Shionogi, Entasis, La Jolla, T2 Biosystems: Advisor/Consultant