Daniel B. Chastain’s research while affiliated with Albany College of Pharmacy and Health Sciences and other places

Fidaxomicin may exhibit cross-reactivity in patients with known macrolide allergies. In this analysis, compared to patients without macrolide allergies, the odds of fidaxomicin allergy were 2.31, 8.37, and 1.58 times higher in patients with azithromycin, clarithromycin, and erythromycin allergies, respectively; the absolute risk of fidaxomicin allergy was 0.033, 0.01, and 0.039 in patients with azithromycin, clarithromycin, and erythromycin allergies, respectively. The highest risk of anaphylaxis and angioedema was observed within 1 year of a non-fidaxomicin macrolide allergy.

Anthropogenic climate change, primarily driven by greenhouse gas emissions, is reshaping ecosystems and creating conditions that affect 58% of all known human infectious diseases, including fungal infections. Specifically, increasing temperatures, changing precipitation patterns, and extreme weather events are influencing fungal growth, distribution, and virulence. These factors may expand the geographic range of pathogenic fungi, exposing populations to novel, potentially more virulent, or drug-resistant strains. Simultaneously, human factors such as declining immunity, aging populations, and increased use of immunosuppressive therapies are enhancing host susceptibility. This review explores the intricate relationship between climate change and fungal infections, highlighting pathogens that may demonstrate increased virulence and antifungal resistance, along with emerging novel pathogens. The clinical implications are profound, with increased morbidity, mortality, and the spread of fungal infections into new regions. Immediate action is required to develop policies, educational initiatives, and novel antifungal therapies, enhance early diagnostic capabilities, and address healthcare disparities to mitigate the growing burden of fungal infections.

Background Sporotrichosis is a fungal infection affecting thousands in South America, yet is uncommon globally, where it is not a reportable disease. This leads to a limited understanding of its epidemiology and clinical features. The study aimed to identify and characterize the clinical features, geographic distribution, risk factors, and outcomes of sporotrichosis across a multicenter United States (US)-based network to improve diagnostic and treatment strategies. Methods The study used the TriNetX global research network database to identify patients with sporotrichosis defined by ICD-10-CM code B42. A manual chart review was conducted to verify the reliability of the code in 60 patients. Data collected included demographics, comorbidities, lab results, and outcomes. The primary outcome was mortality and hospitalization. Bivariate analysis was performed to compare survivors with non-survivors in one year. Results The study included 2,124 patients with sporotrichosis, with a manual chart diagnosis validation rate of 95%. The average age was 52, with 56% women and 40% Caucasian. Common comorbidities were neoplasms, diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD). Most cases were unspecified, but among those with a specified subtype, lymphatic was the most common (9.4%), followed by disseminated (1.1%). Itraconazole was the most common first-line treatment. The one-year mortality was 17% (Table 1). The Southeast had the most frequent cases in the US (Figure 1). Age, unmarried marital status, and location in south or international regions were significantly associated with mortality. Higher ferritin levels, lower hematocrit, and higher leukocyte count also indicated increased mortality (Table 2). There were 17 patients with both sporotrichosis and HIV; 82% were men with an average age of 56. The average CD4 count was 65.5, with a one-year mortality of 17.6% (Table 3). Conclusion Patients with sporotrichosis had low rates of extracutaneous disease. Age, unmarried marital status, geographic location, and specific comorbidities such as neoplasms, DM, and COPD are significant factors affecting sporotrichosis survival. Despite their compromised immune status, patients with HIV did not have worse outcomes than the general sporotrichosis population. Disclosures George R. Thompson, III, MD, Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant

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

Background Coccidioidomycosis (cocci) poses therapeutic challenges due to the variability in disease presentation and severity, particularly for immunocompromised patients. Treatment approaches for cocci have not changed in decades. Fluconazole may remain ineffective as a first-line option in refractory cases or in more invasive disease. We aim to identify a cohort of patients diagnosed with cocci and their treatment pathways using a "real world" international global health network database.Table 1.Characterization of patients undergoing treatment for coccidiomycosis including clinical characteristics and clinical outcomes. Methods We conducted a multicenter retrospective study by querying TriNetX, a global research network, identifying patients with cocci by ICD-10-CM codes and linking to antifungal therapy. We investigated comorbidities diagnosed before infection and outcomes of interest after 1 year. Treatment pathways were assessed within 3 months post-diagnosis. A line of treatment was defined as receipt of the same medication within 3 days of cocci diagnosis, and was considered complete once absent from the patient’s record for 3 consecutive days. Graphs were designed with R Studio (3.6.0).Figure 1.Treatment pathways in coccidioidomycosis Sunburst diagram of initial treatment choices for cocci. A. Treatment pathways for the entire patient cohort diagnosed with coccidioidomycosis B. A subset of the treatment pathway analysis that removes patients with fluconazole monotherapy to better visualize other treatments that were used. Each ring represents a line of treatment. The inner side of the ring is the initial treatment choice, while subsequent rings represent switches. Each switch was defined by taking the same medication for 3 days within coccidioidomycosis diagnosis followed by the receipt of a different medication for at least 3 consecutive days. Results We captured 1909 patients diagnosed with cocci, of which 1581 (82.9%) had treatment pathway information. Most patients were white females around 51 years of age, presenting with pulmonary cocci (52%). Common comorbidities included T2DM (38.3%), CKD (30.9%), concurrent neoplasm (25.1%), and post-transplant-status (18.9%) (Table 1). Candidiasis was present in 14.9% of patients and CMV in 7.2%. Overall, 1-year mortality was 11%. Fluconazole was the most common initial therapy (87.4%) followed by amphotericin B (6.45%), echinocandins (2.34%), and itraconazole (1.83%). Of these, 11.2% of patients were switched to at least one new agent, with the most common switch being fluconazole to amB (1.6%) and amB to fluconazole (1.8%); 1.5% of patients were treated with ≥ 3 total antifungal agents (Fig 1). Conclusion Fluconazole remains the preferred initial agent to treat cocci; only 12.6% of patients received an alternative agent. Most initial switches favored amB, raising concern for treatment failure with fluconazole. Unveiling clinical characteristics of those patients may reveal possible clinical predictors of failure or situations where amB may be preferred. Disclosures George R. Thompson, III, MD, Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant

Background Current research on risk factors for invasive fungal infections (IFIs) in multiple myeloma (MM) has limitations due to heterogeneous patient populations, including post-transplant, or reliance on subgroup analyses. This study aimed to address this gap by evaluating the incidence of IFIs and identifying risk factors in patients with MM receiving treatment before or ineligible for transplant. Methods We analyzed data from the Merative MarketScan Database (2017-2021) to identify adults (≥ 18 years) diagnosed with and treated for MM with proteasome inhibitors, lymphodepleting agents, thalidomide or derivatives, anti-SLAMF7 monoclonal antibodies, or exportin 1 inhibitors, with or without dexamethasone. We evaluated the incidence and risk factors for IFIs following anti-MM therapy initiation. All patients were followed for at least one year. Patients without an IFI were censored at the end of the study period. Results Among 3054 individuals with MM, 6% (n=195) were diagnosed with an IFI. Candidiasis was most common (87%), followed by pneumocystis (6.2%) and aspergillosis (3.6%). Patients with an IFI were younger with a higher burden of comorbidities compared to those without an IFI (table 1). Notably, neutropenia, thrombocytopenia, chronic heart failure, chronic liver failure, hypercalcemia, and hyperglycemia were significantly more common in the IFI group. Anti-MM therapies were similar between groups, with a high prevalence of both thalidomide or derivatives and dexamethasone (table 2). Antifungal prophylaxis was uncommon while nearly half of each group received antibacterial prophylaxis. Patients with an IFI were more likely to have received multiple lines of anti-MM therapy. Multivariate analysis identified recent dexamethasone use (HR 5.85, 95% CI: 4.08-8.40), neutropenia (HR 2.77, 95% CI: 1.87-4.11), and a greater number of anti-MM therapies within the preceding year (HR 2.15, 95% CI: 1.71-2.69) as significant risk factors for IFI. Conclusion Candidiasis was the most common IFI in patients with MM. Younger age, higher comorbidity burden, and neutropenia were associated with IFIs. Additionally, recent dexamethasone use and a higher number of prior anti-MM therapies significantly increased the risk of IFIs. Disclosures All Authors: No reported disclosures

Background Candidemia remains a critical concern in healthcare settings due to its high mortality rates and increasing prevalence of multidrug-resistant strains. Understanding the impact of different Candida species on patient outcomes is crucial for effective management and treatment strategies. This study aims to comprehensively analyze the association between Candida species and mortality in candidemia cases. Percentages of 1-year mortality by Candida species. Methods We queried TriNetX, a global research network database (https://trinetx.com/), to identify patients with positive candidemia in blood by PCR testing from 2020-2023. We captured mortality as the primary outcome at one year in patients with candidemia categorized by Candida species. The time to death within the one year period was assessed using Kaplan-Meier plots, along with the non-parametric log-rank and Peto-Peto tests. Additionally, Cox proportional hazards (PH) models, both unadjusted and adjusted for demographic and comorbidity covariates, were employed for comparative analysis. Unadjusted Kaplan-Mier Survival analysis with failure estimates in candidemia by Candida species Results We captured 1,233 candidemia episodes during the study period. The distribution of Candida species was C. albicans (498, 40.4%), C. glabrata (333, 27%), C. auris (151, 12%), C. parapsilosis (121, 9.8%), C. tropicalis (59, 5%), C. krusei (28, 2%), and poly-candidemia (44, 4%) (Table 1). The one-year mortality varied across species, ranging from 15.3% to 36.6% (Figure 1). The unadjusted Kaplan-Mier Survival analysis showed that poly-candidemia, followed by C. tropicalis, had a worse survival than C. auris, which had the lowest risk (Figure 2). Adjusted Cox PH model found C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and poly-candidemia had statistically significantly higher mortality rates than C. auris. Additionally, age, non-Hispanic ethnicity, residence in the Western US region, and a higher Charlson comorbidity index value emerged as independent predictors of increased mortality (Table 2). Clinical features by Candida species Conclusion Among patients with candidemia, we found an overall 1-year mortality of 28%. The associated resistance of C. auris may translate into a decreased virulence and a survival advantage. Additionally, older age and a higher comorbidity burden were associated with 1-year mortality. Disclosures George R. Thompson, III, MD, Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant

Background Cases of candidemia surged during the COVID-19 pandemic, possibly due to the intensive treatments used in critically ill patients. This study aims to explore the impact of the pandemic on risk factors and clinical outcomes associated with candidemia. Methods We retrospectively analyzed patients ≥ 18 years diagnosed with candidemia at a single facility in Albany, Georgia, between January 2017 and May 2023. Patients were categorized into three groups based on their COVID-19 status and admission date (January 21, 2020, marking the first US case): 1) pre-pandemic (before January 21, 2020), 2) pandemic with COVID-19 (after January 21, 2020), and 3) pandemic without COVID-19 (after January 21, 2020). We compared risk factors for candidemia and in-hospital mortality across these groups. Results A total of 89 patients were included, with 44% pre-pandemic and 56% during the pandemic (half with COVID-19) (Table 1). Baseline characteristics were similar, except for a higher median number of comorbidities in the pre-pandemic group (p=0.008). Notably, the COVID-19 group had a significantly higher proportion of patients with no comorbidities (12%) compared to the pre-pandemic (0%) and pandemic without COVID-19 (4%) groups (p=0.01). Patients with COVID-19 were predominantly diagnosed with candidemia in the ICU (92%) compared to pre-pandemic (49%) and pandemic without COVID-19 (44%) groups (p< 0.001). Additionally, mechanical ventilation and vascular catheters were more frequent in the COVID-19 group (88% and 96%, respectively) compared to the pre-pandemic (31% and 62%) and pandemic without COVID-19 (40% and 68%) groups (p< 0.001 for both) (Table 2). While immunosuppressive medications were uncommon, glucocorticoid use was significantly higher in the COVID-19 group (76%) compared to the pre-pandemic (18%) and pandemic without COVID-19 (24%) groups (p=0.008). In-hospital mortality was highest among patients with COVID-19 (76%) compared to patients before the pandemic (44%) and those without COVID-19 during the pandemic (32%) (p< 0.005). Conclusion Patients with COVID-19 displayed a higher prevalence of candidemia risk factors and significantly worse clinical outcomes, including higher in-hospital mortality, compared to the other groups. Disclosures All Authors: No reported disclosures

Understanding the impact of different Candida species on patient outcomes is crucial for effective management and treatment strategies. This study aims to comprehensively analyze the association between Candida species and mortality in documented candidemia. We queried TriNetX, a global research network database, to identify patients diagnosed with candidemia through polymerase chain reaction from 2020-2023. The primary outcome was mortality in candidemia patients, categorized by Candida species at 90 days and one year. The time to death was assessed using Kaplan-Meier plots. Cox proportional hazard (PH) models were also used for comparative analysis, unadjusted and adjusted for demographic and comorbidity covariates. We captured 1,234 candidemia episodes during the study period. The 90-day and 1-year mortality rates for the various Candida species were as follows: C. tropicalis (33.9% and 35.6%), C. glabrata (28.3% and 34%), multispecies (27.7% and 36.4%), C. parapsilosis (25.8% and 31.8%), C. krusei (21.4% and 28.6%), C. albicans (21.1% and 23.9%), and C. auris (13.3% and 15.9%). The unadjusted Kaplan-Meier Survival analysis showed that multispecies candidemia, followed by C. tropicalis, had the lowest survival. The adjusted multivariable Cox PH model found that C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, and multispecies candidemia had significantly higher mortality rates than C. auris. Age and a higher Charlson comorbidity index value emerged as independent predictors of increased mortality. Among patients with candidemia, we found an overall 1-year mortality of 28%. Multispecies candidemia, C. tropicalis, older age, and a higher comorbidity burden were associated with the highest mortality rates.