bluuebunny/crossref_metadata_2025 huggingface dataset:
P-641. Distinct Cytokine Profiles in Severe Community-acquired Pneumonia and Metabolic Dysfunction-associated Steatotic Liver Disease
Authors: Gjurasin Branimir , Radmanic Matotek Leona , Jelicic Mia , Papic Neven
Published: January 2025

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been identified as a risk factor for severe community-acquired pneumonia (sCAP) outcomes. While MASLD is associated with chronic systemic inflammation, cytokine responses in patients with sCAP and MASLD have not been characterized. The aim of this study was to analyze differences in concentrations and kinetics of cytokines in sCAP patients with and without MASLD.

Methods

A prospective cohort pilot study included patients hospitalized with sCAP defined according to IDSA criteria. Upon admission, clinical and laboratory data were collected, and liver fibroelastography was performed to determine the presence of liver fibrosis and steatosis. Serum concentrations of 13 cytokines (IL-4, IL-2, CXCL10, IL-1β, TNF-α, CCL2, IL-17A, IL-6, IL-10, IFN-γ, IL-12p70, TGF-β1 and IL-8) were analyzed using a multiplex bead-based assay by flow cytometry at admission and on day 5 of hospitalization.

Results

Thirty-eight patients (26 males, median age of 69, [IQR 61-79] years) with sCAP (SOFA 3 [IQR 2-4], PaO2/FiO2 186 [IQR 150-241]) were included. Of them, 18 (47.4%) had MASLD. There were no differences in age, sex and baseline disease severity between the groups. Patients with MASLD more frequently had components of metabolic syndrome. Etiology was identified in 66%, most commonly influenza (50%) and S. pneumoniae (18%). There were no differences in routine laboratory findings at admission, except for lactate, urea, AST, ALT and LDH which were higher in the MASLD group. While at admission we observed no differences in cytokine concentrations, on the 5th-day patients with MASLD had significantly higher concentrations of CXCL10, IL-10, TNF-α, and lower TGF- β1. Both groups had similar cytokine kinetics with significant decreases in CXCL10, CCL2, IL-10, IL-8 and IL-6. However, distinct temporal changes were observed for TGF-β1 and IL-2 which increased only in patients without MASLD.

Conclusion

In conclusion, MASLD is associated with distinct cytokine profiles and kinetics in sCAP. A better understanding of cytokine changes could potentially help elucidate the complex and aberrant immune responses in MASLD patients during sCAP.

Disclosures

All Authors: No reported disclosures
P-660. Exploring the Association Between Helicobacter Pylori Infection and Bronchiectasis: A Meta-analysis
Authors: Yadav Rukesh
Published: January 2025

Background

Helicobacter Pylori (H. pylori) is known to cause various malignancies, and autoimmune disorders. However, the potential association between H. pylori and bronchiectasis has been not analyzed in the literature before. Thus, we aimed to explore the potential association between bronchiectasis and H. pylori.

Forest plot showing the odds of association between H pylori seropositivity and bronchiectasis

Methods

Pubmed, Google Scholar and Embase databases were searched from inception till January 2024 for studies that investigated H. pylori seropositivity, anti H pylori IgG level, urea breath test (UBT) positivity, polymerase chain reaction (PCR) and culture to detect H pylori in gastric juice (GJ) and bronchoalveolar lavage fluid (BALF) in bronchiectasis and matched healthy controls. Outcomes included odds ratio of association between H. pylori and bronchiectasis, detection rate of H. pyroli in BALF, GJ or bronchial biopsies, standardarized mean difference (SMD) of serum anti H pylori IgG level between the bronchiectasis patients and the healthy controls. The analysis was performed in Revman 5.4 software.

Forest plot showing serum anti H. pylori IgG levels between bronchiectasis and healthy controls

Results

Five studies comprising 455 participitants were included in this analysis. H. pylori seropositivity was nearly significantly associated with increased odds of having bronchiectasis. [Odd’s ratio=2.13, Confidence Interval (CI)=1.00-4.53, I2=53%, P value =0.05]. Moreover, the serum anti H. pylori IgG levels were significantly higher in bronchiectasis patients as compared to healthy controls . [SMD=0.37, CI=0.03-0.72, I2=62%, P value =0.03]. However, none of the studies isolated H. pylori from bronchial biopsies in both the bronchiectasis patients and the healthy controls. Interestingly, a study by Teke et al. found that nine patients (22%) of the 41 bronchiectasis patients and three patients (18.8%) of the 16 the controls had positive BALF on PCR, but this was not significantly different between the two groups. The other study by Gulhan et al. however did not find H. pylori on BALF PCR in any of the 26 bronchiectasis patients.

Conclusion

Though the H pylori seropositivity was associated with bronchiectasis, further future studies of larger sample sizes need to be conducted. Further, newer methods to detect H. pylori in bronchiectasis patients need to be explored to prove the association owing to higher H. pylori seropositivity in the general population.

Disclosures

All Authors: No reported disclosures
P-671. Clinical and Laboratory Findings of Measles in Hospitalized Adolescents and Adults in Romania: A Retrospective Study
Authors: Neagu Daniela G , Mangaloiu David V , Molagic Violeta , Tiliscan Catalin , Stratan Laurentiu M , Staicu Isabela D , Adamescu Aida I , Daniel Miron Victor , Sandulescu Oana , Streinu Cercel Anca , Draganescu Anca C , Pitigoi Daniela , Paraschiv Simona , Apostolescu Catalin G , Arama Stefan S , Arama Victoria
Published: January 2025

Background

Despite the availability of efficient and safe vaccines, measles remains a significant public health threat worldwide. In Romania, there has been a resurgence of measles since March 2023, leading up to an outbreak in early December, with many cases reported including among the adult population. Consequently, this study aims to present the epidemiological, clinical, and laboratory data of adolescents and adults hospitalized for measles.Table 1.Patient demographics, clinical, paraclinical and complications characteristics.

Methods

We conducted a retrospective analysis which included 87 patients, aged over 14 years, with measles admitted to National Institute of Infectious Disease „Prof. Dr. Matei Balș”, Bucharest, Romania, between July 2023 and April 2024. For all included patients the diagnosis of measles was serologically confirmed. Demographic, epidemiological, clinical and laboratory data were collected for each patient.

Results

Our results are summarized in Table 1. In brief, the mean age of the participants was 30.82 ± 12.90 years and 57.5% were males. Most of them (89.8%) had no chronic conditions. The most frequent symptoms and signs presented at admission were rash (100%), fever (98.9%) and cough (94.3%). Koplik spots were found in 81.6% of patients. A total of 8% of patients had a full history of MMR vaccination, while 9.2% had been vaccinated with only one dose. The most common laboratory parameter findings were increased C-reactive protein (100%), lymphopenia (95.4%) and liver cytolysis (80.5%). The median duration of hospitalization was 5 days. Pneumonia (74.7%) was the most frequent complication and acute respiratory failure (ARF) was reported in 16.1% of patients. The presence of at least one chronic condition increased the risk of ARF 3.5-fold (p=0.036), and prolonged the duration of hospitalization by at least one day.

Conclusion

The ongoing measles outbreak in Romania highlights significant gaps in adolescents and adults vaccination and immunity. The data underline the severe impact of measles in adults, particularly those with unmanaged chronic conditions, leading to extended hospitalization and complications. This study emphasizes the need for improved vaccination strategies and public health policies to mitigate the measles threat effectively.

Disclosures

All Authors: No reported disclosures
P-713. Two Seasons of Admissions Screening for Influenza and RSV Among a Highly Immunocompromised Patient Population
Authors: Odom Robin T , Forrester LaToya A , Michelin Angela , Scaletta Joseph , Han Alison , Henderson David K
Published: January 2025

Background

To facilitate early detection and prompt isolation of infected patients during the 2022-23 and 2023-24 fall/winter seasons, the NIH Clinical Center, a clinical research hospital serving a significantly immunocompromised patient population, augmented symptom screening with Influenza and RSV testing of all patients on admission.

Methods

Nasopharyngeal (NP) swabs were collected on admission from November 2022-April 2023 and September 2023-April 2024. All samples were tested for Influenza and RSV by PCR on the Panther Fusion® SARS-CoV-2/FluA/B/RSV Assay (Hologic, Inc.) or the Xpert® Xpress CoV-2/Flu/RSV test. Patients who disclosed symptoms on admission were tested using the BioFire® Respiratory Panel. Medical chart reviews and discussions with patient care providers elucidated whether cases identified on admission were asymptomatic.

Results

Of 3197 NP swabs collected from patients admitted to our hospital, 31 swabs were from patients who were symptomatic on admission. Of the remaining 3166 NP swabs (from 2352 unique patients, as some patients had multiple admissions), 17 patients were found to be infected: 7 (0.22%) Influenza A, 1 (0.03%) Influenza B, and 9 (0.28%) RSV. Of these patients that were asymptomatic on admission, 8 (47%) subsequently disclosed symptoms (1 with recent confirmed diagnosis of Rhinovirus/Enterovirus infection), 2 (12%) disclosed a recent history of an unknown respiratory infection, and 7 (41%) were asymptomatic. Seven Influenza A and 8 RSV infections were detected between the months of November and January, yielding positivity rates of 0.57% and 0.66%, respectively, during these months when community transmission was highest.

Conclusion

Admission surveillance for Influenza and RSV during months of increased community transmission allowed us to isolate seventeen patients on admission who would likely not have been appropriately isolated based on symptom screening alone. Admission surveillance testing, in conjunction with symptomatic surveillance, is important to identify infected patients promptly during increased respiratory virus activity in the community, and especially for institutions serving immunocompromised patients.

Disclosures

All Authors: No reported disclosures
P-737. Highly Resistant Myroides Species Infections: Insights from a Comprehensive Case Series and Antibiogram Analysis
Authors: Toiv Avi , Doshi Neal , Ishak Angela , Lanfranco Odaliz Abreu
Published: January 2025

Background

Myroides species (spp.) are rare opportunistic gram-negative bacteria that are highly resistant to commonly used empiric antibiotics. Able to survive in natural and hospital environments, these microbes pose a growing risk of resistant nosocomial infections. Here we present a case series and antibiogram of Myroides infections at an academic medical center, highlighting this potential pathogen’s antibiotic sensitivity to aid clinicians in choosing effective antimicrobial therapies.

Antibiogram

Methods

Retrospective chart review of all patients diagnosed with Myroides spp. infection at Henry Ford Health between January 1, 2019 and December 31, 2023. Patient characteristics, treatments, and outcomes were analyzed. An antibiogram of Myroides spp. susceptibility to 10 antibiotics was generated.

Results

A total of 43 patients (median age 62 yr; range 30-94) presented with 46 Myroides spp. infections. Positive cultures were evenly distributed between hospitalizations (50%) and outpatient (50%) settings. Of the 46 infections, 35 (76%) were in a lower extremity wound. Of the 43 patients, 17 (40%) had sepsis at presentation, including 8 (13%) with Myroides bacteremia. Most Myroides spp. cultures (83%) grew additional organisms, including E. faecalis (34%), S. aureus (21%), Proteus mirabilis (21%), and Pseudomonas spp. (16%). Empiric antibiotics were prescribed in 35/46 cases (76%), mostly vancomycin (17/35) and cefepime (9/35); however, Myroides spp. were sensitive to the empiric agents in only 4 cases (11%). Antibiogram analysis showed 100% susceptibility to meropenem and 0%-50% susceptibility to 9 other agents (Table). A total of 5 (12%) patients died, and 6 patients (14%) required readmission within 1 month of treatment.

Conclusion

Myroides spp. exhibited significant resistance to most empiric antibiotics. Our antibiogram analysis revealed meropenem as the sole effective empiric antibiotic for this opportunistic pathogen. We recommend the prompt empirical use of meropenem when Myroides spp. are identified on antimicrobial culture.

Disclosures

All Authors: No reported disclosures
P-744. Admission Avoidance: A Protocol for Using Dalbavancin in the Emergency Department for Acute Bacterial Skin and Skin Structure Infections
Authors: Weller Katherine , Bland Christopher M , Jones Bruce M
Published: January 2025

Background

Dalbavancin is a glycopeptide with a 14.4 day terminal half-life that has been used previously in our institution to facilitate early discharge for acute bacterial skin and skin structure infections (ABSSSI). We have expanded this program with a pharmacist-driven protocol for use in the emergency department (ED) to avoid admission in ABSSSI for selected patients. The goal of this study was to evaluate the protocol for dalbavancin use in the ED for patient selection and financial impact.

Dalbavancin Emergency Department Protocol

Inclusion/Exclusion criteria for assessment to receive dalbavancin

Methods

This was a retrospective, multi-center, study performed in a community health system from June 2022 through March 2024 of patients who presented to the ED with ABSSSI, evaluated by pharmacist and physician, and discharged directly after receiving dalbavancin. Inclusion and exclusion criteria were based on the patient's symptoms, type of infection, and comorbidities (Figure 1). Data collected included clinical signs/symptoms of infection, previous antibiotic use, history of substance abuse or methicillin-resistant Staphylococcus aureus (MRSA), renal function, and readmissions. Direct costs and reimbursement, as well as if they received patient assistance, were also tracked. The primary objective was to evaluate adherence to the protocol for use of dalbavancin in the ED. The secondary objective was to analyze the financial impact to the health system.

Table 1 & Table 2

Patient Demographics & Clinical Signs/Symptoms

Results

A total of 57 patients met inclusion/exclusion criteria and were evaluated. Patient demographics associated with adherence to protocol are summarized in Table 1. A majority of patients had failed oral therapy and were expected to be admitted for > 3 days. Six patients (10.5%) were re-admitted within 30 days, similar to national averages. Only 2 patients self-reported as persons who inject drugs (PWID). Table 2 summarizes clinical signs/symptoms associated with diagnosis of ABSSSI for the included population. Most patients met multiple diagnostic criteria, with erythema, tenderness, & swelling all reported >75%. For the secondary objective, patients as part of the ED visit had ∼$3800 average reimbursement per patient not including direct and indirect costs of care.

Conclusion

Pharmacists can help identify and facilitate appropriate patients to receive dalbavancin within a structured protocol to help prevent admissions for ABSSSI.

Disclosures

Christopher M. Bland, PharmD, FCCP, FIDSA, BCPS, Merck: Honoraria|Nestle/Seres: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria Bruce M. Jones, Pharm.D., FIDSA, BCPS, AbbVie: Advisor/Consultant|AbbVie: Honoraria|Ferring: Honoraria|Innoviva: Honoraria|Paratek: Honoraria
P-749. Prognostic Determinants in Patients with Necrotizing Fasciitis in a Referral Hospital in Nicaragua
Authors: Hernández-Hernández Francisco , Porras-Cortés Guillermo D
Published: January 2025

Background

Necrotizing fasciitis is a serious condition in which timely diagnosis and therapeutic approaches, both medical and surgical, play an essential role in prognosis. In Nicaragua, the prognostic determinants for this clinical condition in different hospital institutions have not been formally evaluated. The aim of this study was to establish factors that could be determinant for the prognosis of patients with necrotizing fasciitis in a national referral hospital.Table 1.Organ Failure at the Admission in Patients with Necrotizing Fasciitis

Methods

This is a retrospective, cross-sectional, analytical study. It was conducted with patients over 15 years of age with a diagnosis of necrotizing fasciitis hospitalized between January 201 and December 2023 in Dr. Fernando Vélez Paiz Hospital in Managua, Nicaragua. Clinical factors such as comorbidities or organ failure on admission, as well as the LRINEC score, and the times of administration of the first dose of antibiotic and surgical intervention were analyzed and correlated with the clinical outcome of the patients.Table 2.Potentials Prognosis Determinants in Necrotizing Fasciitis that were Evaluated

Results

A total of 45 patients were included in the study, 60% of whom were women. The mean age was 56.0 ± 14.6 years-old. 86.7% of patients had at least one comorbidity. At the time of diagnosis, 31.1% of patients had renal insufficiency, 24.4% had shock, and 15.6% had altered state of consciousness (Table 1). 25 patients died for a mortality rate of 44.4%. The mean time from suspected diagnosis and administration of the first dose of antibiotics was 2.5 ± 1.4 hours (Table 2). Only 20% of patients received the first dose of the antibiotic at the first hour. 17.8% of patients underwent surgery within 6 hours of diagnosis. There was no association between prognosis and the time of initiation of antibiotic therapy and the time of initiation of surgical treatment after diagnosis of necrotizing fasciitis, probably due to a problem of sample size. 60% of the deceased had LRINEC ≥ 8 points, while only 28% in the group of survivors, OR(95%CI): 3.85 (1.10-13.46) (Table 3).Table 3.LRINEC and Mortality in Patients with Necrotizing Fasciitis

Conclusion

Patients with necrotizing fasciitis mostly have comorbidity, mainly diabetes, and almost a quarter of them have shock and a third have renal failure. A LRINEC score greater than or equal to 8 points significantly increases the risk of death in this type of patient.

Disclosures

All Authors: No reported disclosures
P-783. Bedaquiline for the Treatment of Non-tuberculous Mycobacterial Infections: Retrospective Analysis from a Large Healthcare System
Authors: Hysell Kristen , Albin John , Shen Edmund , Hurtado Rocio M
Published: January 2025

Background

Infections from non-tuberculous mycobacteria (NTM) cause significant morbidity and mortality. NTM species are typically highly drug-resistant, requiring prolonged courses of multiple antimicrobials with toxicities and side effects. Bedaquiline, a diarylquinolone approved for treatment of multidrug-resistant tuberculosis, has been shown to have bacteriostatic activity against NTM and appears clinically effective in small case series. We aimed to describe clinical characteristics, tolerability, and treatment outcomes in patients treated with bedaquiline for NTM infections at Mass General Brigham (MGB).

Survival time after starting bedaquiline

Methods

The study was approved by the MGB Institutional Review Board. Electronic medical records were manually reviewed to include all patients treated with bedaquiline between January 2012 through December 2023 for culture-positive pulmonary NTM infection. Kaplan-Meier estimates were used for duration of treatment and survival.

Time from bedaquiline start to stop

Results

There were 31 patients treated with bedaquiline for NTM infection; 21 patients had pulmonary infection and 10 had non-pulmonary infection (6 skin/soft tissue, 2 bone/joint, 2 disseminated). Median age at start of treatment was 56 years (IQR 44, 64). 11 patients (35%) were male, 20 patients (65%) were female. 7 patients (23%) were immunocompromised. 39% had Mycobacterium avium complex and 52% had Mycobacterium abscessus. Bedaquiline was used as salvage therapy for 15 patients (48%) and as oral step-down from an intravenous regimen for 13 patients (42%). Median time from first positive culture to any NTM treatment initiation was 1.3 months (IQR 0.5, 4.6) and median time from first positive culture to bedaquiline start was 29 months (IQR 6.7, 65). 19 patients (61%) underwent surgery in addition to medical management. Culture clearance was documented in 14 patients (45%). 6 patients (19%) experienced drug toxicity while on bedaquiline. 9 patients (29%) died during the follow up period.

Conclusion

This is the largest case series reported to date on the use of bedaquiline for NTM infection. While limited by the retrospective nature and single institutional experience, this analysis suggests bedaquiline may have an evolving role in a multidrug treatment regimen and further analysis in larger cohorts is warranted.

Disclosures

All Authors: No reported disclosures
P-786. Rates of Treatment Discontinuation over Time with Rifampin versus Isoniazid for Latent Tuberculosis Infection: A 6-year Experience at a Large Safety-Net Clinic
Authors: Martins Maria F , Teran Plasencia Juan M , Sinha Pranay , Acuña-Villaorduña Carlos
Published: January 2025

Background

Treatment of latent tuberculosis infection (LTBI) is a crucial component of tuberculosis (TB) eradication plans in the United States (US). It is estimated that 80% of active TB cases arise from LTBI reactivation. Numerous gaps have been identified in the LTBI care cascade, leading to low rates of treatment initiation and completion. Treatment duration has shown to be a significant factor influencing completion rates for LTBI treatment. Since 2020, the Center for Disease Control and Prevention (CDC) recommends 4 months of daily rifampin (4R) as the preferred regimen for LTBI, while 6 to 9 months of isoniazid (9H) is now considered an alternative regimen.Table 1.Characteristics of the Patients by Drug Used

Methods

We conducted a retrospective cohort analysis including all patients treated for LTBI with 4R or 9H (May 2015 - September 2021) at the Boston Medical Center/Boston Public Health Commission TB Clinic. The primary objective was to compare completion rates between patients with LTBI treated with 4R versus 9H. For this, completion of 95% of the planned course was considered sufficient. We also compared rates of treatment discontinuation by plotting a survival curve. Data analysis was performed with R statistical software (version 4.3.2). The study was approved by the Institutional Review Board (IRB) of Boston University.Figure 1.Rates of Treatment Discontinuation over Time for Rifampin versus Isoniazid

Results

A total of 2178 patients with a median age of 40 years-old were treated for LTBI during the study period, 958 (43.99%) with 4R and 1220 (56.01%) with 9H (Table 1). The completion rates differed significantly, with 652 (68.1%) completing 4R compared to 550 (45.1%) completing 9H (p < 0.001). A Kaplan-Meier curve showed similar rates of discontinuation over time between the 2 regimens (Figure 1). After adjusting for key confounders using multivariable logistic regression model, the sole variable significantly associated with LTBI treatment completion was the use of 4R with an odds ratio of 2.805 (95% CI: 2.313 - 3.406) (p < 0.001) (Table 2).Table 2.Factor's Association with Treatment CompletionOR: odds ratio; CI: confidence interval

Conclusion

Our findings confirm that 4R has better completion rates than 9H. Importantly, treatment completion on the survival curve was similar in the first 4 months of therapy, supporting the notion that treatment duration is a key factor determining LTBI treatment completion rate regardless of the drug used.

Disclosures

All Authors: No reported disclosures
P-791. Contribution of tuberculin skin test for diagnosing tuberculosis disease in pediatric patients in Bangladesh
Authors: Sosa Soto Giordano , Hossain Farzana , Rahman Toufiq , Rahman Mahfuzur , Kulkarni Suchitra , Roy Tapash , Malik Amyn , Brooks Meredith
Published: January 2025

Background

Bangladesh has a high tuberculosis (TB) burden, accounting for 4% of pediatric patients estimated to have TB globally. Obtaining microbiological confirmation of disease in children is challenging; in lieu of this, diagnosis often relies on the presence of symptoms, exposure history, physical examination, and a variety of other test results, such as chest x-rays and tuberculin skin tests (TST). We evaluate the contribution of TST to pediatric TB diagnoses.

Methods

An enhanced patient-finding initiative was implemented across 109 facilities in Mymensingh division, Bangladesh (2018-2021) to improve pediatric TB detection. Among children who screened positive on systematic verbal symptom screening and whose subsequent evaluation for TB disease included TST, we report the discriminatory properties of TST for TB diagnosis. We compare patient characteristics between children with positive and negative TST results using chi-squared/Fisher’s exact test.

Results

Of 20,209 children who screened positive on verbal symptom assessment and were further evaluated for disease, 7,318 (36.2%) patients had TST, of which 1598 (21.8%) were diagnosed with TB disease. Discriminatory properties of TST were: sensitivity of 42.2% (95% Confidence Interval: 39.8-44.7%), specificity of 92.4% (91.7-93.1%), PPV of 60.9% (58.3-63.4%), and NPV of 85.1% (84.6-85.7%) (Table 1). A total of 648 (40.6%) children with TB and 364 (6.4%) children without TB had an induration diameter of >10mm (Table 2). Among children diagnosed with TB, fewer males (p=0.01) and children aged 5-9 years (p< 0.01), and more children aged 10-14 years (p< 0.01), underweight (p< 0.01), presenting with night sweats (p=0.02) and decreased appetite (p=0.04), and had a chest x-ray (p< 0.01) or smear (p=0.01) suggestive of TB disease had a positive-TST result compared to children with negative-TST results. Among children with a negative TST result, those who were underweight were diagnosed with TB more often than those not underweight (p< 0.01) (Table 3).

Conclusion

TST can be a clinically helpful part of diagnostic algorithms for children. Given its high specificity and NPV, TST can be combined with an evaluation of clinical symptoms and diagnostic studies to help diagnose or rule out disease in children at risk of TB.

Disclosures

Amyn Malik, MBBS, MPH, PhD, Analysis Group, Inc: Former Employee. Worked as a consultant with Pharma and Biotech for research studies
P-792. Evaluation of the efficacy and safety of a short-course, daily, 4-month regimen including isoniazid, pyrazinamide, rifapentine and moxifloxacin (2HZPM/2HPM) for the treatment of drug-susceptible pulmonary tuberculosis in Taiwan (ESCAPE-TB): A multicenter study
Authors: Feng Jia-Yih , Shu Chin-Chung , Lin Shu-Min , Weng Ya-Wei , Chen Jui-Kuang , Wu Kuan-Sheng , Tsai Hung-Chin , Chen Yao-Shen , Lin Hsi-Hsun , Shin-Jung Lee Susan
Published: January 2025

Background

The world is not on track to end the TB epidemic by 2030. Efficacious, safe, and shorter treatment regimens may significantly improve treatment success rates, and reduce TB incidence and mortality. The aim of this study is to evaluate the efficacy and safety of a short-course, 4-month regimen (2HZPM/2HPM) in the Asian population.

Methods

A prospective, 3-year, interventional study (Jan 2021-Dec 2023) enrolled adults with pulmonary TB, compared to historical controls (1:2 ratio) matched by age and sex, receiving standard 6-months treatment. The primary outcome was TB disease-free survival at 12 months after treatment assignment and proportion of grade 3 or 4 adverse events. A short-course regimen included a 2-months daily isoniazid(H), pyrazinamide(Z), rifapentine(P), and moxifloxacin(M), and 2 months of HPM. Sputum cultures were collected to assess early bactericidal effect at 2 months and to detect relapse at 12 months post-treatment.Fig 2.Treatment Duration of short-course, 4-months vs standard 6 months anti-tuberculous treatment: intent-to-treat analysis

Results

109 subjects received short-course therapy, (80 males), with a mean age of 63.4 +/- 15.9 years; and 218 controls. Rates of adverse events were higher in the treatment group but were mostly Grade 1 (54.3% vs 28.7%, p < 0.001), and not significant for Grade 2 (p=0.28), Grade 3 (p=0.59) or Grade 4 (p=0.39). A higher discontinuation rate was found in the treatment group (65.7% vs 35.7%, p < 0.001). Reasons for discontinuation included: hyperbilirubinemia, GI upset, dizziness and others. Currently, 74.1% of the treatment group has completed treatment, 14.8% are under treatment, and 3.7% died, not related to TB. 2-months sputum culture conversion was 86.5 vs 93.4% (p=0.15), in the treatment versus control group, respectively. Survival at 12 months post-treatment was not significantly different between the treatment versus control group (91.7% vs 90.6%, p=0.17). Significant risk factor for treatment discontinuation included age >=55 years (adjusted HR 3.23, 95% CI: 1.27-8.19, p=0.01).

Conclusion

A short-course, 4 months regimen containing HPZM may be as efficacious as current standard, 6-month, anti-TB treatment regimens in Asian patients. Our study demonstrated a high rate of treatment discontinuation in Asian patients. This may be due to the older age of subjects with lower tolerability to adverse events.

Disclosures

All Authors: No reported disclosures
P-795. Unravelling the Enigma: Evaluating False Positive and Invalid Results in Urinary TB LAM Test among HIV Patients with Opportunistic Infections
Authors: Sharma Shivang , Kumar Deepak
Published: January 2025

Background

Various studies suggested that successful implementation of urine Lateral Flow –Lipoarabinomannan (LF LAM) testing could greatly improve TB diagnosis and treatment in HIV patients.Studies from India are scarce regarding urine LF-LAM testing. One should be careful while interpreting the positive test as this test can be positive in NTM, or nocardiasis. This case study highlights the false positive test result of LF-LAM testing and its impact on clinical decision-making in HIV TB co-infection.

Methods

In,this prospective observational hospital based study total 95 adult patients had been included consecutively regardless of their presenting symptoms or CD4 count.During this study, all recruited patients were underwent for relevant investigation for diagnosing opportunistic infections including TB and simultaneously urine LF-LAM assay tests were performed during hospitalisation.Urine LF- LAM testing had been conducted using the Determine Ag assay and interpreted using the 4-grade scale provided by the manufacturer.

Results

Out of total 95 patients, 31 were diagnosed with TB, and 25 tested positive for LAM. However, among the 25 LAM-positive patients, five were found to have false-positive results, while two patients received invalid results. Among the six cases of false-positive TB LAM results, three patients had confirmed NTM (Non-tuberculous mycobacterial) infections, one case was culture-positive for nocardiosis, and another had Cryptococcal infection. One case involved urosepsis with Diabetic Ketoacidosis. All five cases were negative for ZN stain, GeneXpert, and TB culture, and no ATT was administered. Tragically, two patients among these five expired. Additionally, both patients with invalid results had chronic kidney disease.

Conclusion

There can be false-positive TB LAM results with several clinical conditions like NTM infections,Nocardiosis,cryptococosis.These clinical conditions are close differential diagnosis of TB and requires invasive or advance testing methods. While urinary TB LAM testing demonstrates promising sensitivity in diagnosing tuberculosis among hospitalized HIV patients, the occurrence of false-positive results and invalid result outcomes alert clinicians and one should exercise caution in interpreting TB LAM results.

Disclosures

All Authors: No reported disclosures
P-801. Epidemiology and Clinical features of 101 Patients with Aeromonas Bacteremia
Authors: Masuda Daisuke , Furukawa Keiichi
Published: January 2025

Background

Recently pts with Aeromonas bacteremia have been increasingly recognized at our hospital. We investigated epidemiology and clinical features of pts with Aeromonas bacteremia at Asahi General Hospital (980 beds, acute care general hosp. Japan).

Methods

We retrospectively reviewed the medical records of all pts with positive blood cultures for Aeromonas from Jan1, 2018 to Sept30, 2023. We investigated characteristics of the pts , history of well water use , focus of infections, species , antimicrobial susceptibility, therapy, and 30-day mortality.

Results

Total 101 pts with Aeromonas bacteremia were included. We had average 20 A. bacteremia cases per a year and the number was much higher than other reports. Well water was used at home in 66%(21/32) of the pts. Male 69%(p=0.23),Median age 79 (42-97), Almost all pts(98%) had baseline diseases : malignancy 54%, cancer of biliary tract or liver 36%, diabetes mellitus 26%,steroid or immunosuppressant use 5%chr. renal diseases 5%, chr. liver disease 3%. Community acquired infect. was 81%. Hepatobiliary tract infect. was the most common 77%, (cholangitis 67%, cholecystitis7%, liver abscess 2%), septic shock unknown focus 6%, urinary infect. 3%, peritonitis 2%, skin soft tissue infect. 2% , others 11%. A.caviae was predominant 63%, A.veronii 20%, A.hydrophila17%. Mixed bacterial infect. 58%. Antimicro. suscept.(%) : PIPC/TAZ97, CMZ78, CTX89, CFPM100, MEPM97, LVFX100. The 30-days mortality rate(%) was 20 (21/101) in total and was relatively high in PIPC/TAZ therapy 34(15/44), followed by CTX 17, CTRX17, MEPM17, CMZ8,and CFPM0, LVFX0, CPFX0. The 30-days mortality rates by species(%): A.hydrophila 29, A.veronii25, A.caviae 17, Mixed infect. 22.

Conclusion

We had many pts with Aeromonas bacteremia , which might be related to well water use of many pts in our district. Most of the pts were elderly, having baseline diseases including cancer(54%) and hepatobiliary tract infect. was most common. The 30-day mortality rate was lowest in the therapy group with CFPM or LVFX .

Disclosures

All Authors: No reported disclosures
P-805. Factors associated with mortality and morbidity of patients with methicillin-resistant Staphylococcus aureus bacteremia in a regional hospital
Authors: Choy Annabel K T , Tang Tommy H C , Wu T C , Leung W S
Published: January 2025

Background

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is a critical health issue. This retrospective study aimed at identifying factors associated with adverse clinical outcomes in MRSA bacteremic patients admitted to Kwong Wah Hospital, an 800-bed regional hospital in Hong Kong, China. It was approved by the Kowloon Central/Kowloon East Cluster Research Ethics Committee, Hospital Authority (KC/KE-23-0107/ER-4).

Methods

Patients aged 18 years or above with MRSA bacteremia between 2020 and 2022 were identified. Their demographics and clinical background were summarized in Table 1. The primary and secondary outcomes were 30-day all-cause mortality and intensive care unit (ICU) admission, respectively.

Results

Of the 115 patients included, 112 (97.4%) received intravenous vancomycin as the first line antibiotic, 59 (51.3%) developed complicated bacteremia and 17 (14.8%) necessitated second line antibiotics (Figure 1). Thirty-six (31.3%) died within 30 days of positive blood culture for the first time and 14 (12.2%) needed ICU care.

Among the 44 (38.3%) patients attended by an infectious disease (ID) doctor, there was a higher chance to receive echocardiogram (77.3% vs 56.3%), computed tomography (52.3% vs 8.45%), surgical removal of infective foci (43.2% vs 12.7%), and numerically lower deaths (20.5% vs 38.0%) compared to those who were not.

ID consultation, along with younger age, lower Charlson comorbidity index, longer duration of antibiotics, and those without altered mental status or hypothermia, were noted to favor survival in univariate analysis (Table 2). By multivariate logistic regression, older age, higher C-reactive protein, altered mental states, and shorter antibiotic duration were significantly associated with mortality while ID consultation, vancomycin MIC >= 1 μg/mL, and congestive heart failure were associated with ICU admission (Table 3).

Conclusion

MRSA bacteremia resulted in high mortality. ID consultation might have contributed to a greater effort in searching for surgically removable infective foci and a numerically lower death rate. Its association with ICU admission might suggest that sicker patients require greater expertise from ID doctors.

Disclosures

All Authors: No reported disclosures
P-806. How close are we to achieving the trifecta of optimal treatment duration, route of therapy, and repeat blood culture testing for uncomplicated gram-negative bacteremia?
Authors: Son Andrea H , Morelli Morgan K , Hecker Michelle T
Published: January 2025

Background

A 2021 consensus document outlined recommendations for treatment duration, oral antibiotic use, and need for repeat blood cultures in patients with uncomplicated gram-negative bacteremia. Data support 7 days of effective therapy and oral step-down therapy in clinically stable patients. Repeat blood cultures were not recommended except for patients with concern for endovascular infection. We sought to evaluate the percentage of our gram-negative bacteremia cases that would be defined as uncomplicated and how well our practices for these cases aligned with the 2021 recommendationsTable 1.Antibiotic days of therapy

Methods

This retrospective cohort study included adult patients hospitalized between 1/1/2022 and 12/31/22 who had a blood culture with growth of a gram-negative organism and who received ≥ 4 days of antibiotics for the bacteremia. Effective therapy required both use of an antibiotic to which the organism was susceptible and source control. Unnecessary IV therapy was defined as continuation of IV therapy in patients with clinical stability for ≥ 24 hours who had an oral treatment option available.Table 2.Repeat blood cultures

Results

During 2022, 251 unique patients were hospitalized with gram-negative bacteremia and received ≥ 4 days of antibiotics, 130 (52%) of whom were classified as having uncomplicated bacteremia. The average duration of effective therapy was 11.8 days and 74.6% of patients received ≥ 10 days. Unnecessary IV therapy was continued for an average of 3.8 days and 33 (34%) were not transitioned to an orally available option by day 4 of clinical stability. Repeat blood cultures were done in 86 (66%) patients but were indicated in only 18 (14%). Twenty-two (26%) repeat blood cultures were collected < 48 hours after the initial positive blood culture

Conclusion

Using the 2021 consensus recommendations as a guide, more than half of patients with uncomplicated gram-negative bacteremia at our institution received longer than recommended durations of therapy, were not transitioned to an oral option when clinically stable and had repeat blood cultures done when not indicated. A multifaceted intervention to achieve the trifecta of optimal treatment duration, route of therapy, and repeat blood culture testing for uncomplicated gram-negative bacteremia is planned.

Disclosures

All Authors: No reported disclosures
P-807. Evaluation of Risk Factors for Carbapenem-Discordant Enterobacterales Bacteremia at a Large Academic Cancer Institution
Authors: Stabler Alex , Vuong Nancy , Borjan Jovan , Hwang Hyunsoo , Feng Chun
Published: January 2025

Background

Carbapenem resistance in non-carbapenemase producing Enterobacterales is thought to be mediated by increased beta-lactamase production and outer membrane porin mutations. Cases of phenotypic discordance of carbapenem susceptibility (ertapenem-nonsusceptible, meropenem-susceptible) are documented. Given limited clinical data in immunocompromised patients, we aim to characterize risk factors that may lead to carbapenem-discordant Enterobacterales (CD-E) bloodstream infection (BSI) in patients with cancer.

Methods

This is a retrospective, single-center study comparing adults > 18 years of age from January 2016 through November 2023 with a history of a ceftriaxone-resistant Enterobacterales (CRO-R-E) BSI subsequently having either a CRO-R-E or CD-E BSI of the same index organism within one year. Fisher’s exact test was used to compare categorical variables. Wilcoxon rank-sum test was used for continuous variables. Univariate logistic regression models were used to evaluate risk factors associated with CD-E BSI development.

Results

We evaluated 829 patients with CRO-R-E BSI. 9.4% had a subsequent CRO-R-E BSI and 1.6% developed CD-E BSI with the same index organism. The most common organisms identified were Escherichia coli (n=70, 76.9%) and Klebsiella species (n=16, 17.6%). There was no difference in age and most patients had a hematologic malignancy (n=83, 91.2%). Subsequent CRO-R-E or CD-E BSI occurred most often within 90 days of the index BSI (n=61, 78% and n=11, 85%, respectively). Ceftazidime-avibactam (CZA) and latter generation cephalosporin exposure were each significantly associated with CD-E BSI (OR 10.29; p< 0.001 and OR 1.05; p=0.03, respectively). Severe neutropenia (absolute neutrophil count < 500 K/µL) trended towards significance for CD-E BSI development (OR 3.41, p=0.06). Of the 13 CD-E BSI, development of nonsusceptible carbapenem-concordant phenotype with the same organism in the following year occurred in 5 patients (38.5%).

Conclusion

These data suggest that risk factors associated with CD-E BSI development include exposure to CZA or latter generation cephalosporins. Severe neutropenia may also be an indicator, but further studies are warranted to validate this and other CD-E BSI risk factors.

Disclosures

All Authors: No reported disclosures
Mock Court simulations—what is their influence on preparing police officers for the reality of presenting testimony in a court case?
Authors: Davies Amanda , McCarthy Catherine
Published: January 2025

The preparation of police recruit officers as police witnesses in judicial hearings is critical in contributing to the accuracy and completeness of information in the prosecution of alleged offenders and ultimately to judicial decisions. There is a paucity of studies focused on strategies for preparing police officers for their role in court hearings. This article presents the evaluation of the design and delivery of a Mock Court simulation exercise in preparing police recruits for the reality of this future operational role. The findings from participant surveys and interviews indicate the Mock Court simulation exercises enable participants to more adequately transition theory to practice and is an essential experience for building competence and confidence for their future policing duties. The key elements of the Mock Court simulation design and environment that evoke engagement, presence, and immersion in the simulation are discussed to contribute to the wider police education community endeavours.
BASDAI and ASDAS disease states in relationship to ASAS40 response: post-hoc analysis of ixekizumab in radiographic axial spondyloarthritis
Authors: Rudwaleit Martin , Navarro-Compán Victoria , Russ Hagen , Panni Tommaso , Filippi Erica , Nassab Mani Haschemi , Liu-Leage Soyi , Goëb Vincent , Ciccia Francesco , Dudler Jean
Published: January 2025

Objectives

To explore the relationship between Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Axial Spondyloarthritis Disease Activity Score (ASDAS) used in clinical practice and the Assessment of SpondyloArthritis international Society 40 (ASAS40) response, the primary endpoint in clinical trials in axial spondyloarthritis (axSpA).

Methods

Data from COAST-V, a phase 3 trial of ixekizumab versuss placebo in biologic-naïve radiographic axSpA (r-axSpA) patients, were analysed. Patients treated with ixekizumab every 4 weeks were categorized using ASAS40 response at week 16 and 52. The association between BASDAI and ASDAS disease states, respectively and ASAS40 response achieved/not achieved was investigated. Additionally, back pain, fatigue, Bath Ankylosing Spondylitis Functional Index, ASAS Health Index, and 36-item Short Form Health Survey Physical Component Summary scores corresponding to these states were assessed. Results were reported descriptively.

Results

After 16 weeks, 48.1% (39/81) patients achieved an ASAS40 response. Among them 71.8% (n = 28) and 43.6% (n = 17) achieved BASDAI < 3 and BASDAI < 2, respectively; 76.9% (n = 30) and 33.3% (n = 13) attained ASDAS < 2.1 and ASDAS < 1.3, respectively. Among ASAS40 responders at week 52 (53.1%; 43/81), 83.8% (n = 36) and 51.2% (n = 22) patients achieved BASDAI < 3 and BASDAI < 2, respectively; 93.1% (n = 40) and 41.9% (n = 18) attained ASDAS < 2.1 and ASDAS < 1.3. Lower BASDAI and ASDAS disease states corresponded well with less back pain, fatigue, functioning impairment, and better health-related quality of life.

Conclusions

More than 70% of biologic-naïve r-axSpA patients who achieved an ASAS40 response, also attained low disease activity or inactive disease as measured by BASDAI or ASDAS. Findings may help clinicians translate results from clinical trials into daily practice.
Cross-trait GWAS in COVID-19 and systemic sclerosis reveals novel genes implicated in fibrotic and inflammation pathways
Authors: Rosa-Baez Carlos , Borrego-Yaniz Gonzalo , Rodriguez-Martin Inmaculada , Kerick Martin , Acosta-Herrera Marialbert , Martín Javier , Ortiz-Fernández Lourdes
Published: January 2025

Objectives

Coronavirus disease 2019 (COVID-19) and SSc share multiple similarities in their clinical manifestations, alterations in immune response and therapeutic options. These resemblances have also been identified in other immune-mediated inflammatory diseases where a common genetic component has been found. Thus, we decided to evaluate for the first time this shared genetic architecture with SSc.

Methods

For this study, we retrieved genomic data from two European-ancestry cohorts: 2 597 856 individuals from The COVID-19 Host Genetics Initiative consortium, and 26 679 individuals from the largest genomic scan in SSc. We performed a cross-trait meta-analyses including >9.3 million single nucleotide polymorphisms. Finally, we conducted functional annotation to prioritize potential causal genes and performed drug repurposing analysis.

Results

Our results revealed a total of 19 non-HLA pleiotropic loci, including 2 novel associations for both conditions (BMP1 and PPARG) and 12 emerging as new shared loci. Functional annotation of these regions underscored their potential regulatory role and identified potential causal genes, many of which are implicated in fibrotic and inflammatory pathways. Remarkably, we observed an antagonistic pleiotropy model of the IFN signalling between COVID-19 and SSc, including the well-known TYK2 P1104A missense variant, showing a protective effect for SSc while being a risk factor for COVID-19, along with two additional novel pleiotropic associations (IRF8 and SENP7). Finally, our findings provide new therapeutic options that could potentially benefit both conditions.

Conclusion

Our study confirms the genetic resemblance between susceptibility to and severity of COVID-19 and SSc, revealing a novel common genetic contribution affecting fibrotic and immune pathways.