Treatment Regimens Research Articles

Evaluation of the effect of some treatment regimens of dry cows with genital Mycoplasmosis on the protein metabolism of their offspring

Modern political realities force us to rely on the development of our own agricultural production in order to ensure the country's food independence. To achieve this goal, it is necessary to increase its production while increasing profitability. In industrial animal husbandry, the main reserve for the implementation of this task is to reduce the incidence of animals and obtain healthy offspring from them. In this regard, the development of inexpensive and effective ways of diagnosing treatment becomes relevant. This is of the greatest importance for a group of diseases characterized by a long latent period and erased symptoms, which include genital mycoplasmosis of cattle. The purpose of the research was to study the use of the antibacterial drug tulatromycin and its combination with the immunomodulator thymalin in pregnant cows with genital mycoplasma on the protein metabolism of their calves. To conduct the experiment, three experimental groups of calves from cows with genital mycoplasmosis were formed, calves from clinically healthy animals served as controls. The total protein, protein fractions, classes of immunoglobulins and their proportion in the globulin fraction were determined in all groups. During the experiment, it was found that calves from infected cows have pronounced dysproteinemia. The use of tulathromycin for the treatment of cows leads to a partial restoration of the content of immunoglobulins in their offspring, whereas the combination of both tulathromycin and thymalin applied to pregnant cows ensures the restoration of all studied indicators in calves born by them to the level of their healthy peers.

Natural compounds as modulators of miRNAs: a new frontier in bladder cancer treatment.

Bladder cancer (BC) is a major global health issue with a high recurrence rate and limited effective treatments. Over the past few years, it has become evident that miRNAs play a role in the carcinogenesis process, particularly in regulating genes that promote cancer cell proliferation and invasion. This review focuses on the extent to which natural products can act as potential miRNA modulators for the management of bladder cancer. Polyphenols, flavonoids, and other phytochemicals are natural compounds found to have inherent potential to modulate miRNAs and reform the oncogenic properties of bladder cancer cells regulating cell growth and death. In integration with the current cancer treatment regimes, such natural agents may safely substitute for the traditional chemical chemotherapeutic agents of the conventional approaches. To this end, this review presents the existing knowledge of natural compounds as regulators of miRNA, their mechanisms for the management of BC, the role of their nanoparticles, and future novel therapies. The use of these compounds is not only a therapeutic practice for the conditions of bladder cancer, but it also upholds new avenues for creativity.

Decoding the Implications of Zinc in the Development and Therapy of Leukemia.

Zinc plays a central role in the hematological development. Therapeutic interventions with zinc are shown to improve the health status of patients with malignancies by stimulating the immune system and reducing side effects. Despite the abnormal zinc homeostasis in leukemia, the role and mechanisms of zinc signaling in leukemia development remain poorly understood. Recently, some important breakthroughs are made in laboratory and clinical studies of zinc in leukemia, such as the role of zinc in regulating ferroptosis and the effects of zinc in immunotherapy. Zinc-based strategies are urgently needed to refine the current zinc intervention regimen for side-effect free therapy in chemotherapy-intolerant patients. This review provides a comprehensive overview of the role of zinc homeostasis in leukemia patients and focuses on the therapeutic potential of zinc signaling modulation in leukemia.

P-72. The Evaluation of Pressure Injury Associated Pelvic Osteomyelitis in Patients with Spinal Cord Injuries in a Veterans Affairs Population

Abstract Background Limited data, and thus no clinical guidelines, are available for the treatment of pelvic osteomyelitis with associated pressure injuries (PI) in spinal cord injury (SCI) patients. Treatment of SCI patients with PI-associated osteomyelitis at the Veterans Affairs (VA) involves a multidisciplinary team including SCI, infectious disease, wound care, and surgery specialists. Herein we describe the management and outcomes of an SCI cohort with PI-associated pelvic osteomyelitis. Methods A retrospective chart review of patients ≥ 18 years of age, with a culture-positive clinical diagnosis of PI-associated pelvic osteomyelitis, treated by the SCI service between January 1, 2018, and October 1, 2023, was conducted. Patient characteristics, treatment choice, duration, and surgical intervention were compared between those with treatment failure versus success. Treatment failure was defined as having either microbiologic relapse, chronic suppressive therapy, or death due to the osteomyelitis during treatment. Differences between groups were assessed by Fisher’s exact test. Results A total of 31 patients were identified, the majority were male (97%) with a median age of 66 years (Table 1). There were 17 patients with histopathology analyzed at diagnosis, of which 88% were positive. Majority of the cultures obtained were bone cultures (71%). The cultures were primarily polymicrobial with 45% growing MRSA (methicillin resistant Staphylococcus aureus) and low Pseudomonas aeruginosa rates (13%). Majority of patients underwent surgical debridement (61%) and received prolonged durations of antibiotics beyond 6 weeks (Table 2). A total 8 (26%) patients experienced treatment failure. Surgical management and prolonged durations of antibiotics did not differ significantly between the groups. Patients in the treatment success group had lower rates of beta-lactam as a component of their treatment regimen. Conclusion Only a quarter of the SCI patients with PI-associated pelvic osteomyelitis failed treatment. Significantly more patients in the treatment success group had non-beta lactam containing treatment regimens. Larger studies are warranted to shed light on optimal management of pelvic osteomyelitis in this population. Disclosures Jaclyn A. Cusumano, PharmD, BCIDP, Basilea Pharmaceutica: Grant/Research Support

P-64. Variations in the treatment of Cutibacterium acnes Infections of the Bones and Joints and Associated Outcomes

Abstract Background Cutibacterium acnes is an emerging pathogen in bone and joint infections. While treatment guidelines recommend the use of β-lactam therapy for C. acnes infections, the lack of routine susceptibility testing may result in wide variation in treatment regimens among physicians. We assessed the treatment regimens chosen by physicians for patients with bone and joint infections with C. acnes and the treatment outcomes of β-lactam and non-β-lactam regimens. Methods This was a multi-center, historical cohort study comparing treatment regimens in patients diagnosed with C. acnes for both native and prosthetic bone and joint infection. The study included patients with monomicrobial cultures positive for C. acnes and diagnosed with septic arthritis, prosthetic joint infections, osteomyelitis, or discitis between 7/1/2018- 6/30/2023. Data collected included antimicrobial therapeutic regimens, surgical intervention, as well as treatment failure and success. Data were analyzed using chi square test, Student’s t-test, and the Mann-Whitney U test. Results Among 49 included patients, 65.3% of infections resulted from prosthetic joint infection, 26.5% from osteomyelitis, and 8.2% from septic arthritis. The most common intravenous antibiotics chosen to treat C. acnes were ceftriaxone (51%), vancomycin (16.3%), and penicillin (6.1%) with a mean treatment duration of 43.4 days. The most common oral antibiotic treatment was doxycycline (20.4%), amoxicillin (18.4%), cephalexin/cefadroxil (12.2%) with a median outpatient treatment duration of 38 days (range 5, 364). Overall, there were no difference in treatment outcomes between patients treated with β-lactams vs, non-β-lactams at six months, including cure (58.8% vs. 71.4%, p=0.53), persistence of symptoms (26.5% vs. 14.3%, p=0.49), recurrence (17.6% vs. 28.5%, p=0.51), and requiring suppressive therapy (23.5% vs. 28.6%, p=0.78), respectively. Conclusion Physicians preferred β-lactam antibiotics for treating patients with bone and joint infections caused by C. acnes. There were no differences in outcomes for treating C. acnes bone and joint infections between β-lactam and non-β-lactam antibiotic regimens. Further studies should be performed to confirm this observation. Disclosures All Authors: No reported disclosures

P-2027. Care at Home for Remdesivir Treatment of COVID-19: A Mixed Methods Study of Patient and Physician Experiences

Abstract Background Hospital in the home and virtual models of care were rapidly implemented during the COVID-19 pandemic. We sought to assess patient and provider perspectives of care at home integrating a three or five-day remdesivir (RDV) treatment regimen in a large integrated health care system in California.Figure 1.Patient Survey Recruitment Consort Flow Diagrama. Identified as unreachable prior to and during recruitment (deceased, no longer health system members, cognitive impairment, invalid contact information)b. Lost to follow- no response after exhausting all contacts Methods A mixed methods study was conducted to assess patient and physician experiences using an online/telephone survey questionnaire developed based on components of the Health Belief Model and Hospital Consumer Assessment of Healthcare Providers. Patients > 18 years of age who received RDV in the outpatient setting (N=1544) and prescribing physicians (N=406) from December 15, 2020-August 31, 2022 were eligible. Descriptive statistics were used to describe categorical responses. A cross-sectional analysis was performed to identify factors associated with patient adherence defined as taking > 80% of prescribed doses and physician adoption of treatment guidelines. Qualitative data were triangulated to determine whether patient/prescriber perceptions about value were validated by health outcomes measured as reduction of COVID-19 related readmission within 30 days of entry into treatment program.Figure 2.Provider Survey Recruitment Consort Flow Diagrama. No longer health system providersb. Lost to follow-up- no response after exhausting all contacts Results Of 540 patient respondents (response rate: 38%, mean age: 58.4 years (SD 16.2), 55.2% male), the majority was of Hispanic ethnicity (48.4.2%), followed by White (32.3%), and Black (12.6%). Of 140 physician respondents (response rate: 34%, mean age: 46.9 years (SD 8.4), 58% male), the majority was of Asian ethnicity (65.8%), followed by White (23%), and Hispanic (7.1%). Adherence was found in 99% of patients having completed > 80% of RDV doses. Adherent patients reported returning to their own home (95.2%), nurses always listened to them (87%), and high health literacy (65%). Feeling knowledgeable was significantly associated with physician prescribing of new unfamiliar medications while under emergency use authorization. (p=0.0007). Patients (80.3%) reporting “Very Satisfied” with medical follow-up were less frequently readmitted within 30 days. (p=0.045) Conclusion Patients and physicians responded favorably to value-based care at home integrating RDV for treatment of COVID-19. This finding is key to informing future design of alternative modes of health care delivery. Disclosures Julia K. Nguyen, PharmD, Gilead Sciences: Grant/Research Support Rulin C. Hechter, MD, PhD, MS, Gilead Sciences: Grant/Research Support William Towner, MD, GSK: Grant/Research Support|Janssen: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support

P-1496. Retrospective Study of Ceftazidime-Avibactam Treatment for Multidrug-Resistant Gram-Negative Bacterial Infections in King Chulalongkorn Memorial Hospital

Abstract Background Antimicrobial resistance, particularly among Enterobacterales, poses a significant healthcare threat. With the rise of carbapenem-resistant strains, alternative treatment strategies are necessary. This study explores the clinical experience of using ceftazidime-avibactam (CAZ-AVI) in treating infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB), including carbapenem-resistant pathogens.Table 1.Baseline characteristics of the patients who received CAZ/AVI Methods A single-center retrospective observational study was conducted at King Chulalongkorn Memorial Hospital, Thailand, from Jan. 2019 to Dec. 2022. The study included adult patients aged ≥18 years, who receiving ≥48 hours of CAZ-AVI for documented MDR-GNB infections. Data on demographics, comorbidities, treatment regimens, and outcomes were extracted from electronic medical records. The primary outcome was all-cause mortality at 14 days. Secondary objectives included clinical and microbiological responses at 14 days, and all-cause mortality at 28 days.Table 2.Clinical outcomes of the patients who received CAZ/AVI Results Among 85 patients receiving CAZ-AVI, 75 met inclusion criteria. The mean age was 65.27 years, with 54.7% being male. Hospital-acquired infections accounted for 82.7%, and 56% were ICU patients. Underlying conditions included chronic kidney diseases/end-stage renal diseases (28%), solid tumors (24%), cirrhosis (13.3%), hematologic malignancies (10.7%), and solid organ transplantation (10.7%). K. pneumoniae was the most common organism (69.3%), followed by P. aeruginosa (20%). All (100%) of K. pneumoniae and E. coli were carbapenem resistance. CAZ-AVI susceptibility was observed in 93.6% of isolates. The 14-day all-cause mortality rate was 25.3%. Clinical and microbiological response rates were 70.7% and 65.3%, respectively. Infection by CAZ-AVI-susceptible organisms correlated with lower mortality rates (p=0.017). No adverse drug effects were reported.Table 3.Clinical outcomes of the patients who received CAZ/AVI Conclusion This study highlights the promising role of CAZ-AVI in treating MDR-GNB infections, offering an alternative to conventional therapies. While challenges remain, including the complexity of empirical therapy and variations in patient outcomes, CAZ-AVI demonstrates efficacy with a favorable safety profile. Disclosures KAMONWAN JUTIVORAKOOL, MD, Msc, Pfizer, Thailand: Grant/Research Support|Pfizer, Thailand: Honoraria Rongpong Reinprayoon, MD, MSc, Pfizer: Grant/Research Support

P-459. Length Of Hospital Stay, In-patient Mortality And Factors Associated With Mortality Among HIV-Cryptococcal Meningitis Patients Receiving Liposomal Amphotericin B At Tertiary Hospitals in Uganda

Abstract Background Cryptococcal meningitis (CM) remains the second lethal opportunistic infection among People Living with HIV (PLWHIV) in sub-Saharan Africa. Currently, the patients are managed on single high-dose liposomal amphotericin B and flucytosine. However, there is no sufficient data on whether the new treatment regimen has an effect on reducing inpatient mortality and length of hospital stay in the real-world setting. We aimed to investigate the proportion of inpatient mortality, length of hospital stay (LOS), and factors associated with mortality among patients with HIV-associated CM receiving liposomal amphotericin B-flucytosine regimen. Methods This was a cross-sectional study conducted to review medical records of patients admitted between December 2022 and May 2023 at 11 tertiary hospitals in Uganda. Medical records of 173 HIV-CM patients were reviewed. Univariate descriptive statistics were used to summarize the background characteristics. Modified Poisson regression was used to ascertain factors associated with mortality at bivariable and multivariable levels. Associations were presented through adjusted prevalence ratios with their 95% confidence intervals. Data were analyzed using STATA v15. Results Of the 173 patients’ medical records reviewed, 58.4% were males with a median age of 38 years (IQR= 30, 48) and over 55.5% were married. Patients with altered mental status (GCS< 15) were 40%. Overall, inpatient mortality for liposomal amphotericin B was 35.8% and this varied by health facility. The median LOS was 7 days (IQR = 3, 12). Factors associated with mortality were convulsion [APR, 1.86, 95%CI (1.21-2.86), p-value=0.005)], altered mental status [APR; 1.66, 95%CI (1.07-2.57), p-value=0.023], and a comorbid condition [APR, 2.26 95%CI (1.44-3.53), p-value=0.006]. Therapeutic lumbar punctures were significantly associated with reduced mortality [APR; 0.47, 95%CI (0.29-0.73), p-value=0.001]. Conclusion Liposomal amphotericin B regimen has lower mortality than deoxycholate in the real-world setting. Patients on average spend more than a week in hospital. Male sex, convulsion, altered mental status, and comorbid conditions were independently associated with mortality. Therapeutic LPs significantly reduced inpatient mortality. Disclosures All Authors: No reported disclosures

P-290. Clinical and microbiological characteristics of patients infected with ceftazidime/avibactam-resistant Klebsiella pneumoniae carbapenemase-producing K. pneumoniae strains

Abstract Background Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae with ceftazidime/avibactam (CZA) resistance emerged after the widely use of CZA. The most common resistance mechanism was mutations in blaKPC. We aimed to study the clinical and microbiological characteristics in patients infected with CZA-resistant KPC-producing K. pneumoniae, and focus on the comparison between the strains with or without KPC variants (wild-type KPC). Methods A retrospective study was conducted in Taipei Veterans General Hospital from February 2019 to July 2023. Hospitalized unique adult patients infected with CZA-resistant KPC-producing K. pneumoniae were included. Clinical characteristics and outcomes were collected, and genes encoding carbapenemases were detected by polymerase chain reaction followed by Sanger sequencing. Results A total of 44 cases with CZA-resistant KPC-producing K. pneumoniae infections were identified, and most of them were critically ill with the median APACHE II score 23.0 (IQR, 19.3-29.8). Pneumonia was the most common infection (n=18). Only 15 patients (34.1%) received appropriate treatment regimens, and tigecycline (n=8) and meropenem-based therapy (n=5) were the common regimens. Twenty-seven strains (61.4%) harbored KPC variants, and a total of 16 different types were identified. KPC-33 (n=10) was the most common, followed by KPC-35 (n=3). The overall 28-day mortality was similar between patients infected with and without KPC variants (22.2% vs 23.5%, p=1.000). A previous isolation of carbapenem-resistant K. pneumoniae and exposure to CZA were more common in KPC variants group compared with wild-type KPC group (92.6% vs 58.8%, p=0.017, 92.6% vs 41.2%, p< 0.001, respectively). KPC variants-producing strains also had a higher proportion of CZA MIC > 16 mg/L (85.2% vs 41.2%, p=0.002) and restored meropenem susceptibility (MIC≤ 4 mg/L) (70.4% vs 5.9%, p< 0.001) than that in wild-type KPC strain. Conclusion CZA-resistant KPC variants-producing K. pneumoniae has the tendency of restored meropenem susceptibility and higher level of CZA resistance compared with the wild type KPC-producing strain. The optimal therapy in these patients needs further study. Disclosures All Authors: No reported disclosures

Effect of Low-Dose Methylprednisolone in Promoting Neurological Function Recovery after Spinal Cord Injury: Clinical and Animal Studies.

Subgroup analysis of a retrospective clinical and animal trial [Study of different doses of methylprednisolone on functional recovery of spinal cord injury]. The aimed to investigate the efficacy of low-dose methylprednisolone regimens in promoting neural repair after SCI. Spinal cord injury (SCI) can result in sensory, motor, and autonomic nerve dysfunction, often leading to disability or death. Methylprednisolone (MP) is a preferred medication for clinical treatment of SCI. Low-dose regimen may be a safer and more effective approach. A subgroup comprising 705 patients with traumatic cervical SCI from four medical centers between January 2015 and December 2020 was retrospectively analyzed. Patients were stratified based on treatment regimen: low-dose methylprednisolone, high-dose methylprednisolone, or no methylprednisolone use. All patients underwent spinal decompression surgery. The degree of neurological recovery and the incidence of complications during follow-up were compared among these three groups. Additionally, we investigated the disparities in neurological function recovery, neuronal death, and neural axon regeneration between the low-dose and high-dose methylprednisolone treatment regimens using a SCI rat model. Patients receiving the low-dose methylprednisolone regimen exhibited superior neurological recovery compared to those receiving the high-dose regimen and those not receiving methylprednisolone (82.0% vs. 74.0%, P=0.030; 82.0% vs. 63.4%, P=0.001). Moreover, patients in the low-dose methylprednisolone group demonstrated the lowest rates of perioperative pulmonary infections and gastrointestinal bleeding among these three groups. Evaluation of the SCI rat model through Basso-Beattie-Bresnahan (BBB) score, footprint analysis, electrophysiological tests, hematoxylin and eosin (H&E) staining, immunofluorescence staining, and Nissl staining further corroborated that the low-dose methylprednisolone treatment regimen enhanced transport function recovery, reduced neuronal death, and promoted neural axon regeneration. The low-dose methylprednisolone regimen may have a more positive therapeutic effect on the recovery of neurological function after SCI than other regimens.

P-1937. Multisystem inflammatory syndrome in children (MIS-C) - Accurate Diagnosis for Targeted Treatment

Abstract Background Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory post-acute COVID-19 condition that clinically overlaps with Kawasaki disease (KD). However, the recommended first-line therapy differs for these two conditions. The Centers for Disease Control (CDC) and centers for state and territorial epidemiologists (CSTE) updated the surveillance case definition for MIS-C in 2023 to improve specificity. Since it has been suggested that 15%-20% of children identified using the 2020 definition will not meet the updated definition. While the incidence of MIS-C has decreased, waning immunity and low vaccine uptake in children requires continued vigilance and research. The objective of this study is to determine the utility of the 2023 CSTE/CDC definition to identify children with MIS-C at a quaternary care pediatric center. Methods Children diagnosed and treated for MIS-C at the Children’s of Alabama (COA) between January 2020 and December 2022 were enrolled in a prospective follow-up study. Demographic, clinical, and laboratory data, and treatment regimens were abstracted from the electronic medical record (EMR). The CDC 2020 and the 2023 CTSE/CDC criteria were applied to the cohort. Results The study cohort includes 126 children diagnosed and treated for MIS-C at COA between 2020 and 2022. The demographic and clinical features are summarized in Table 1. Of the 126 children, 92.8% (117/126) and 93.6% (118/126) respectively met the 2020 and the updated 2023 definition for MIS-C. While 81.7% (103/126) of children were treated with IVIG + steroids, 18% (23/126) were treated with IVIG only. In addition, 12 children required immunomodulators (Anakinra /Remicade /Infliximab) for resolution of symptoms after treatment with IVIG + steroids. Favorable short and mid-term outcomes were documented in all children in this cohort. Conclusion Over 90% of children with MIS-C met the criteria for MIS-C diagnosis with either the 2020 or the revised 2023 definition. The lack of definitive clinical or laboratory biomarkers and significant clinical overlap with other entities makes it challenging to identify all children with MIS-C highlighting the need for a better understanding of the pathogenesis, biomarker discovery, and effective therapies. Disclosures Swetha Pinninti, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Suresh Boppana, MD, GSK: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support

P-1464. Clinical Outcomes of patients with Infection Secondary to VancomycinResistant Enterococci (VRE)

Abstract Background Daptomycin dose dependent VRE infection is a growing clinical challenge to patients and healthcare providers. In this study, we sought to describe patients with infections secondary to Daptomycin-susceptible and dose-dependent VRE. Methods We conducted a retrospective cohort study of adult patients admitted at Ochsner LSU Health Shreveport- Academic Medical Center who were diagnosed with VRE infections between 2019 and 2024. We evaluated risk factors, comorbidities, treatment regimens and clinical outcomes of VRE infections with daptomycin MIC 4 mcg/ml (group 1) vs those with VRE daptomycin MIC < 4 mcg/ml (group 2). Results Out of 85 patients with different VRE infections, 42 (49.41%) had a daptomycin MIC = 4, while 41 (48.23%) had a daptomycin MIC < 4. Different sources of VRE infections were identified among the two groups. Polymicrobial infection rates were 54.76% in group 1 and 60.97% in group 2. History of previous infection with vancomycin-sensitive Enterococcus was observed in 12% of group 1 and 17% of group 2. The majority of Enterococcus isolates were E. faecium: 97.6% in group 1 and 58.5% in group 2. Comparable factors between the two groups included the presence of external lines, coexisting chronic kidney disease (CKD), and previous beta-lactam use. The targeted antibiotics included daptomycin only, linezolid only, or a combination of either one with ceftaroline or a beta-lactam. The duration of daptomycin treatment was 23.86 days in group 1 and 21.8 days in group 2. In group 1, 80.95% received a daptomycin dose higher than the standard dose of 6 mg/kg, compared to 46.34% in group 2. A dose of 10 mg/kg was significantly observed in 33.3% of group 1 and 9.8% of group 2. The 30-day mortality rate in group 1 (MIC = 4) was 11.90%, whereas in group 2 (MIC < 4), it was 14.63%. Conclusion Our data revealed a higher incidence of VRE infections with a MIC = 4 mcg/ml among Enterococcus faecium species. Additionally, VRE infections with a higher MIC = 4 were associated with comorbidities such as chronic kidney disease and the presence of external devices and central venous catheters. Understanding these risk factors can aid in identifying high-risk patient populations and implementing targeted preventive measures. Disclosures All Authors: No reported disclosures

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

Abstract 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-177. Contemporary Clinical Characteristics and Outcomes of Leprosy— a Multicenter Network Analysis

Abstract Background Leprosy, also known as Hansen's disease, is a chronic infectious disease caused primarily by Mycobacterium leprae, endemic to tropical countries. In 2022, WHO registered 165,459 cases of leprosy. We lack more contemporary clinical descriptions and outcomes of the disease. Understanding its clinical characteristics is essential for improving diagnosis, treatment, and patient outcomes. We aim to describe the clinical manifestations and outcomes associated with leprosy using a "real-world" database. US Map of the proportion of captured cases by region Methods We queried TriNetX, a global research network database (https://trinetx.com/), to identify patients with Leprosy by ICD-10 code. We captured demographics, comorbidities, clinical manifestations, treatments, and outcomes within 1 year. Clinical characteristics and outcomes of leprosy patients by region Results We captured 1,237 patients, with 965 (78%) originating from the US health system. The mean age was 48, and most were women (60.4%). US patients were predominantly from the South and West (Figure 1) and were predominantly White, Native Hawaiian, or Asian (table 1). The most common clinical manifestations included neuralgia, rash, neuropathy, and malaise. Blindness, corneal abrasions, and burns were present among 2-3% of US patients. Orchitis, iritis, and the Lucio phenomena were relatively uncommon. Rifampin, dapsone, and minocycline were most commonly used. However, significant geographical differences were noted in treatment regimens. Notably, clofazimine use was minimal. Steroids were used in 60% of cases, with a higher prevalence in US-based patients. Other immunosuppressants were uncommon, although methotrexate use was more frequent internationally. TB co-infection was 2%. The overall 1-year mortality was 24.3%. Clinical characteristics and outcomes of leprosy patients by region Conclusion Women from the southern and western US were the most significantly affected demographic groups. Severe complications like blindness, corneal abrasions, and burns, though less frequent, underscore the potential impact on quality of life. The presence of conditions like TB co-infection and the use of steroids in treatment point to the need for comprehensive preventive care strategies. With an overall 1-year mortality of 24.3%, our findings stress the importance of early diagnosis and treatment to improve outcomes and reduce mortality rates. Clinical characteristics and outcomes of leprosy patients by region Disclosures All Authors: No reported disclosures

P-2336. Efficacy of Treatment Regimens in Achieving Virological Response in Patients with Hepatitis D Virus Infection: A Network Meta-analysis

Abstract Background Despite the availability of treatment options for hepatitis D virus (HDV) management, choosing the most appropriate drug scheme for achieving virological response (VR) has not been adequately studied. Methods We conducted a systematic review and network meta-analysis of randomized trials in PubMed, EMBASE, and Web of Science databases reporting rates of VR (defined as undetectable HDV RNA or decrease by ≥ 2 log10 IU/ml at the end of treatment compared with baseline measurements). Available treatment regimens included interferon-alpha (IFN-alpha), pegylated IFN-alpha (PEG-IFN-alpha), nucleoside analogs (NA), bulevirtide (BLV), lonafarnib (LNF), combination therapy or placebo. We used random effects model and estimated odds ratio (OR) with 95% confidence interval (CI) to compare treatments based on VR. To identify the best treatment, we estimated the surface under the cumulative ranking (SUCRA) curve. Analyses were performed using the meta and netmeta packages in R (version 4.3.3). *Denotes statistically significant associations Results A total of 1322 patients from 21 studies were included in the analysis and were randomized in one of 11 treatment interventions, as described in Figure 1. Treatment duration ranged from 24 to 96 weeks. BLV + PEG-IFN-alpha was ∼6 times more likely to result in VR compared with BLV alone (OR, 5.55 [95%CI: 1.60, 19.25]). Treatment with BLV + PEG-IFN-alpha was ∼17 times more likely to result in VR compared with PEG-IFN-alpha monotherapy (OR, 16.7 [95%CI: 5.6, 49.5]) (Table 1), the main agent recommended by official guidelines for HDV management. Based on probability ranking, the most effective drug schemes for achieving VR at the end of treatment were BLV + PEG-IFN-alpha (99.7%), BLV + NA (84.4%), BLV (78%), and PEG-IFN-alpha (61.3%). Conclusion BLV + PEG-IFN-alpha is superior in achieving VR at the end of HDV treatment compared with all other available drug schemes. Further research to determine whether BLV + PEG-IFN-alpha can maintain long-term VR after end of treatment is needed. Studies should also evaluate the impact of different BLV dosages on VR. Disclosures Eleftherios Mylonakis, MD, PhD, BARDA: Grant/Research Support|Basilea: Advisor/Consultant|Chemic Labs/KODA Therapeutics: Grant/Research Support|Cidara: Grant/Research Support|Leidos Biomedical Research Inc./NCI: Grant/Research Support|NIH SciClone Pharmaceuticals: Grant/Research Support|NIH/NIAID: Grant/Research Support|NIH/NIGMS: Grant/Research Support|Pfizer: Grant/Research Support|Regeneron Pharmaceuticals, Inc.: Grant/Research Support

Orbital inflammatory disease: a joint clinical experience in rheumatology and ophthalmology.

This retrospective study aimed to characterize the clinical features, histopathological findings, and treatment outcomes of patients diagnosed with orbital inflammatory disease (OID) co-managed by the rheumatology and ophthalmology departments in a tertiary hospital. Medical records of 14 patients with OID were analyzed. Data on demographics, clinical presentation, laboratory investigations, radiological imaging, histopathological results, treatment regimens, and disease outcomes were collected and reviewed. The mean age of the patients was 34.5years, with a female (71.4%) predominance. Periorbital pain (62.5%), periorbital edema (50%) and diplopia (50%) were the most common presenting symptoms. Histopathological evaluation revealed diverse subtypes, including non-specific orbital inflammation (NSOI) (42.8%), orbital myositis (28.5%) and IgG4-related disease (14.3%). Initial treatment with systemic corticosteroids achieved remission in 14.3% of patients, while 85.7% required additional immunosuppressive therapy. Radiotherapy was effective in one patient unresponsive to steroid and azathioprine treatment. OID presents with diverse clinical manifestations and histopathological subtypes, often requiring multidisciplinary management. While corticosteroids remain the first-line therapy, adjunctive immunosuppressive agents or radiotherapy may be necessary in refractory cases.

P-566. Long-term virologic outcomes of oral two-drug vs three-drug antiretroviral regimens in children, adolescents and adults living with HIV

Abstract Background Despite the availability and efficacy of two-drug regimens (2DR) for HIV treatment, three-drug regimens (3DR) are mostly used by people with HIV (PWH). We evaluated virologic outcomes of initiating or switching to a 2DR vs 3DR among PWH in Washington, DC. Adjusted Cox Proportional Hazard Regression Model for Virologic Non-Suppression (viral load > 200 copies/mL) among PWH by Two- and Three-Drug Regimens in the DC Cohort, 2019-2023 Methods We included DC Cohort treatment-experienced participants initiating or switching to a 2DR or 3DR on or after July 2019 with ≥2 years of follow-up. Descriptive statistics for demographic and clinical factors at regimen initiation, including HIV viral load (VL) and CD4 count (cells/µL), were stratified by 2DR or 3DR. Multivariable Cox proportional hazard modeling was performed among participants virally suppressed (VS; VL< 200 copies/mL) at regimen initiation to assess the time to non-virologic suppression (non-VS) using adjusted hazard ratios (aHR) and 95% CI adjusting for demographics, HIV risk, and regimen. Among participants who were not VS at the time of regimen initiation, we conducted a sub-analysis of the time to VS. Results We analyzed 1782 participants (72.8% 3DR, 28.2% 2DR (161 switched from a 3DR); age 54.3 years (IQR 43.8-61.3), 68.8% male; 78.1% Black) with a median CD4 621 (IQR 409-868) at regimen initiation. Participants on 2DR were older (56.4 vs 53.6 years; p< 0.001) and had higher VS rates (93.8% vs 88.2%; p< 0.001) at regimen initiation and shorter regimen times (3.2 vs 3.8 years; p< 0.001) compared to 3DR. 2DR participants were more likely to have public vs private insurance and receive hospital vs community-based care. The risk of non-VS was higher among those with CD4 < 200 and 200-500 (aHR 1.5(1.0-2.1) and aHR 2.0(1.1-3.6), respectively) compared to those with CD4 >500. Those with public insurance were also more likely to experience non-VS (aHR 1.5; p< 0.05). While regimen type was not a significant predictor of non-VS, there was an elevated risk among those on 3DR (aHR 1.2) compared to 2DR [Figure]. Among those non-VS at regimen initiation (n=146), the median time to VS was similar among PWH on 2DR (14.1 months) and 3DR (13.8 months; p=0.76). Conclusion Non-VS PWH have similar time to VS regardless of whether they receive 2DR or 3DR, suggesting similar efficacy of 2DR and 3DR in these populations. Patients with CD4 < 500 had higher risk of non-VS on 2DR, supporting the usefulness of the CD4 criteria factor when selecting 2DR vs 3DR. Disclosures All Authors: No reported disclosures

P-581. Racial/Ethnic Disparities of Renal Outcomes in People with HIV (PWH) on Tenofovir Alafenamide (TAF) Based Antiretroviral Treatment (ART) Regimens in the Real World

Abstract Background The risk of chronic kidney disease (CKD) is higher in PWH than HIV-negative persons. Black communities are not only disproportionately affected by HIV but also more at risk for kidney disease than other races. Despite Black PWH generally being underrepresented in clinical trials, the BRAAVE trial showed switching to bictegravir/emtricitabine/TAF demonstrated non-inferior efficacy and similar tolerability, including renal safety, compared to prior ART regimens in this group. With this analysis, we aim to assess whether these trial results translate to the real-world setting among Black PWH using a retrospective cohort analysis. Methods The descriptive analysis was conducted using IQVIA ambulatory electronic medical record (EMR) database (November 2015 – July 2023). The study population included PWH (≥ 18 years) who were newly prescribed with ART regimens. Study endpoints evaluated the incidence of azotemia, Fanconi syndrome, renal tubular acidosis (RTA), renal toxicity, acute kidney injury (AKI), and CKD stages using diagnosis codes, stratified by racial group (Black and non-Black) and treatment with TAF-based regimens using prescription codes. Incidence rates were reported. The analysis was conducted using ATLAS Version 2.12.1. Results Overall, 4,562 Black and 5,946 non-Black PWH were identified on TAF-containing regimen, with 7,933 and 10,198 person-years of follow-up, respectively (Table 1). Compared to non-Black PWH, Black PWH were more likely to be female, have diabetes and hypertension. Black PWH on TAF had a higher incidence of advanced CKD and similar incidence rates of azotemia, renal toxicity, AKI, and RTA compared to non-Black PWH on TAF (Table 2). When stratified by baseline hypertension, no significant differences in the incidence of renal disease were observed between Black and non-Black PWH. There were no cases of Fanconi syndrome in the study cohort. Conclusion Despite the inherent limitations of real-world data, this analysis included a large cohort of Black PWH on TAF-containing ART and showed a low incidence of RTA and AKI, despite predisposition to increased rates of renal decline or safety outcomes in Black PWH starting ART. Disclosures Samir K. Gupta, MD, Gilead Sciences, Inc.: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support Sarjita Naik, PharmD, MPH, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Xiwen Huang, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Amy Weinberg, DNP, MS, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Lauren Temme, PharmD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Li Tao, MD, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Betty Chiang, MD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Anand Chokkalingam, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Jihad Slim, MD, FACP, AbbVie: Grant/Research Support|AbbVie: Honoraria|AbbVie: Speaker Bureau|Gilead Sciences, Inc.: Grant/Research Support|Gilead Sciences, Inc.: Honoraria|Gilead Sciences, Inc.: Speaker Bureau|Merck: Grant/Research Support|Merck: Honoraria|Merck: Speaker Bureau|Theratechnologies: Advisor/Consultant|Theratechnologies: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Speaker Bureau

P-173. An Exploration of the Reported Cases of Acanthamoeba Keratitis

Abstract Background Acanthamoeba keratitis (AK) is a rare manifestation of infection caused by this ubiquitous protozoan parasite. Treatment is complicated by the absence of FDA approved treatments. Here we aim to review reported cases of AK to identify case characteristics and potential successful treatments. WHO Region wise distribution of Acanthamoeba Keratitis Methods All cases of AK from 2012-2024 reported on PubMed (684) and Embase (816) were identified using relevant keywords, MeSH terms and Emtree terms. Rayyan.ai was used to screen cases using PRISMA protocol. Cases meeting inclusion criteria were uploaded to CureID. All AK cases in CURE ID (170) were then analyzed in aggregate. Outcomes in Patients with Acanthamoeba keratitis Results Most cases occurred in the Americas (44.1%), followed by Europe (22.4%) and the least number of cases were contracted in the Eastern Mediterranean (5.3%) region (Figure 1). 76/170 cases of AK showed partial response to the treatment and 12/170 remained unchanged (Figure 2). Table 1 shows the most commonly used medications and their respective outcomes. Figure 4 represents the correlation between type of contact lens used and severity of disease presentation for the 90 cases where this information was available. Most commonly used medications and their respective outcomes Conclusion Although majority of the patients responded to treatment, most did not fully recover, and 4 patients died. This underscores the significant morbidity caused by this disease. We noticed diagnostic delays due to misdiagnoses as fungal or viral eye infections. Improved diagnosis will be vital to improving outcomes. Outcomes appeared to be better with combination therapies that included Chlorhexidine, Propamidine and PHMB. This finding supports the inclusion of these drugs in a standardized regimen for treatment of AK. Conversely, Miltefosine produced mixed results and should be excluded. It also appears that severity of AK may be related to contact lens use and soft contact lenses may be associated with higher severity of AK. We speculate that higher incidences in the Americas and Europe may also be related to higher lens usage. Our aim is to further investigate these correlations through a full manuscript. Lens use V/S No Lens use and severity in presenting symptoms Disclosures All Authors: No reported disclosures

P-529. Comparison of Renal Outcomes by Tenofovir Alafenamide Fumarate (TAF) vs. Tenofovir Disoproxil Fumarate (TDF) Containing Regimens for Prevention, and Treatment of HIV and/or HBV Treatment: A Systematic Literature Review and Meta-Analysis

Abstract Background Tenofovir is one of the most widely used agents for human immunodeficiency virus (HIV) and hepatitis B virus (HBV) treatment, and pre-exposure prophylaxis (PrEP). Two forms of tenofovir are currently available: tenofovir disoproxil fumarate (TDF) and its prodrug, tenofovir alafenamide (TAF). TAF is associated with improved renal safety and non-inferior efficacy when compared to TDF. We aimed to comprehensively synthesize the evidence on renal outcomes of TDF and TAF regimens for treatment of HIV-1, HBV, or PrEP. Methods A systematic search of randomized controlled trials (RCTs) that compared TDF vs. TAF for the treatment of HIV-1, HBV, or PrEP and reported changes in estimated glomerular filtration rate (eGFR) or serum creatinine (SCr) from treatment initiation was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Trial Registry. This search was performed on 12/6/2023 and supplemented a previous review by Gupta et al. (2019). Renal outcomes were pooled using mean differences with 95% confidence intervals (CIs). The heterogeneity was assessed using I2 test and explored via subgroup analyses of disease state and duration of follow-up. Results Out of 9,014 studies screened, 24 RCTs (total 21962 participants; 12756 in TAF; 9206 in TDF) reported eGFR outcomes and 21 RCTs (total 18454 participants; 10293 in TAF; 8161 in TDF) reported SCr outcomes. Compared to TDF, the use of TAF was associated with an improvement of 3.69 mL/min/1.73m2 (95% CI: 1.89 – 5.49) in eGFR from treatment initiation (I2 = 95.83%) (Figure 1). Subgroup analyses of disease state and study duration for eGFR are described in Table 1. The effect sizes were consistent across subgroups, low levels of heterogeneity were observed for analyses lasting > 48 weeks and for HBV. TAF was also associated with an improvement of SCr of 0.03 mg/dL (95% CI: 0.02 to 0.04) from treatment initiation compared to TDF (I2 = 82.47%) (Figure 2). Conclusion This synthesis of RCT results supports a comparative renal safety advantage of TAF over TDF when evaluated across a broad and diverse range of people including those diagnosed with HIV-1, HBV, HIV and HBV coinfection, and those receiving PrEP. Further exploration of sources of heterogeneity and the evaluation of observational study data are needed. Disclosures Kyu Yun Park, PharmD, Gilead Sciences, Inc.: Grant/Research Support Connor Willis, PharmD, ARUENA: Grant/Research Support|AstraZeneca: Grant/Research Support|Bayer: Grant/Research Support|Boehringer Ingelheim: Grant/Research Support|DexCom: Grant/Research Support|Gilead: Grant/Research Support|Gilead Sciences, Inc.: Grant/Research Support|Grail, Inc.: Grant/Research Support|Jazz: Grant/Research Support|Mainstay Medical: Grant/Research Support|Novartis: Grant/Research Support|PEAR Therapeutics: Grant/Research Support Rachel Rogers, Gilead Sciences, Inc.: Employee; Medical writing support provided by Aspire Scientific (Bollington, UK)|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Amy Weinberg, DNP, MS, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Julia Green, MS, APRN, AGNP-C, ACRN, AAHIVE, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Aileen Chi, PharmD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Private Company) Nathorn Chaiyakunapruk, PhD, Gilead Sciences, Inc.: Grant/Research Support