Histoplasmosis is an endemic mycosis caused by Histoplasma capsulatum. Infection develops by inhalation of microconidia from environmental sites inhabited by birds and bats. Disseminated disease is the usual presentation due to impaired cellular immunity. Common clinical manifestations include fever, fatigue, malaise, anorexia, weight loss, and respiratory symptoms. Histoplasma antigen detection is the most sensitive method for diagnosis. The sensitivity of the MVista ® Quantitative Histoplasma antigen enzyme immunoassay is 95-100% in urine, over 90% in serum and bronchoalveolar lavage (BAL) antigen and 78% in cerebral spinal fluid (CSF). A proven diagnosis can be established by culture or pathology with sensitivities between 70% and 80%. The sensitivity of antibody detection by immunodiffusion or complement fixation was between 60% and 70%. Diagnosis using molecular methods has not been adequately validated for implementation and FDA cleared assays are unavailable. Liposomal amphotericin B should be used for 1-2 weeks followed by itraconazole for at least one year until CD4 counts are above 150 cells/mm3, HIV viral load is below 400 copies/mL and Histoplasma urine antigen is negative. Serum itraconazole level should be monitored to avoid drug toxicity. Antigen should be measured periodically to establish that treatment is effective and to assist in identifying relapse. The incidence of immune reconstitution inflammatory syndrome is low but it must be considered in patients who are thought to be failing antifungal treatment as it does not respond to changing antifungal agents but rather to initiation of corticosteroid therapy. In this review, we discuss pathogenesis, clinical manifestations, diagnosis and treatment based on personal experience and relevant publications.

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Background Blastomycosis is an endemic fungal infection that causes pulmonary and systemic disease. It can occur irrespective of the patient's immune status. The risk factors associated with the severity of the disease are not well studied. Methods This is a retrospective study of patients admitted with blastomycosis at the University of Kentucky Hospital from 2004 to 2019. Logistic regression was used to identify variables associated with severe blastomycosis. Results A total of 76 patients were identified; 22 (28.9%) had at least one immunosuppressive condition. Pulmonary blastomycosis was reported in 49/76 (65%) of the patients and disseminated infection in 27/76 (35.5%). All diagnostic tests were not significantly different in diagnostic results in immunocompromised vs immunocompetent patients. Cultures and histopathology were positive in 56/61 (91.8%) and 54/63 (85.7%) respectively. Blastomyces or Histoplasma antigen test was positive in 13/17 (76.4%) in immunocompromised patients compared to 26/42 (61.9%) in immunocompetent patients. Immunocompromised patients were more likely to be admitted to the hospital and ICU compared to immunocompetent patients. In the multivariate analysis, pulmonary multilobar disease (RR 5.68; 95% CI 2.13–15.15), obesity (RR 2.39; 95% CI 1.26‐4.51), diabetes mellitus (RR 3.50; 95% CI 1.38‐8.90) and immunosuppression (RR 2.28; 95% CI 1.14‐4.56) were significant independent risk factors for severe blastomycosis. Inpatient mortality proportion was higher in immunocompromised patients but not statistically significant. Conclusion Pulmonary multilobar disease, obesity, diabetes mellitus and immunosuppression were risk factors associated with severe blastomycosis. Immunocompromised patients required more frequent hospitalisations compared to immunocompetent patients.

Background The Intravenous Drug Use (IVDU) epidemic has been developing into a public health crisis in the last twenty years. As a result, the incidence of severe bacterial infections such as infective endocarditis (IE) has been rising dramatically. Methods Cross-sectional study, we reviewed records of all admissions to University of Kentucky hospitals with IVDU associated ICD9/10 codes who received an Infectious Diseases consult during 2018 and focused on the cases with a diagnosis of IE. We describe associated epidemiologic, clinical, and microbiological features Results We include 391 patients in this cohort, among those 157 patients were for IE. Patients had a median age of 34 years old (range: 20 - 62); 81 (51.5%) were female, and five (6.1%) were pregnant and 153 (97.4%) identified as white. A previous episode of infective endocarditis was reported in 55 (35%) cases. The most common illicit substances used were heroin 68 (43.3%) and methamphetamine 65 (41.45%). Tobacco abuse was reported in 134 (86.4%) cases. Fever reported in 93 (59.8%) cases, shortness of air in 43 (28.0%) cases, and chest pain in 44 (28.6%) cases were the most common symptoms. Hepatitis C antibody was positive in 115/149 (73.2%) and 3/143 (1.9%) were HIV positive. Right-sided IE was more frequent, the tricuspid valve was involved in 94 (59.8%) patients. Gram-positive pathogens were isolated in 139 (88.5%) patients, Staphylococcus aureus was isolated in 102 (64.9%) patients, of which 67 (65.7%) were methicillin resistant. Gram-negative pathogens were isolated in 18 (11.2%) patients. Eighty-eight (56.4%) patients had an addiction medicine consult during their admission, (22.9%) patients left against medical advice and 20 (12.7%) patients needed to be readmitted within 30 days after discharge. Overall mortality was 12.7% and was significantly associated with infection by gram-negative pathogens (RR: 2.5; CI 95% 1.05 – 6.25, p=0.037). Conclusion Infectious endocarditis is a frequent complication in PWID which carries a high risk of mortality and often involves the tricuspid valve. The most common pathogen isolated was S. aureus, isolation of gram-negative pathogens was associated with increased mortality. Disclosures All Authors: No reported disclosures

Background Blastomycosis is an endemic dimorphic fungal infection caused by Blastomyces dermatitidis. The risk factors associated with severe presentation are not well defined. Methods Retrospective study of patients treated for blastomycosis at the University of Kentucky Hospital from 2004-2019. Statistical analyses were performed with STATA version 12.0 (College Station, Texas). Logistic regression was used to identify variables associated with severe infections. Results Among 82 patients, median age was 48 years old (range: 16 - 89); 66 (80.5%) were male and 71 (92.2%) were white, 25/77 (32.4%) were obese, 24 (29.2%) were diabetic, 21 (25.6%) had COPD, 26 (31.7%) had at least one immunosuppressive condition. The median duration of illness was 86 (3-365) days. 37 (45.1%) had cough and 35 (42.6%) had dyspnea 19 (23.1%) patients were treated in the ICU, 42 (51.3%) in non-ICU inpatient wards, and 21 (25.6%) in an outpatient setting. Cultures were obtained in 69 cases, 59 (85.5%) reported as positive, KOH stain positive in 30/61 (49.1%). Histopathology was positive in 48/66 (72.7%) samples. Urine Histoplasma or Blastomyces antigen was positive in 41/58 (70.6%), and Serum Histoplasma or Blastomyces antigen was positive in 22/34 (64.7%). Among 64 (78.0%) patients with pulmonary blastomycosis, acute and chronic pneumonia were 16 (25.0%) and 12 (18.7%) cases respectively, and nodular lung lesions were reported in 36 (56.2%). Initial antifungal treatment was amphotericin B liposomal in 38/80 (47.5%), overall mortality was 11 (13.4%). A multivariable analysis was performed to find predictors of severe blastomycosis infection, no association was seen with factors as male sex (IRR 1.96; 95%CI 0.84 – 4.55), and was confirmed that significant independent associated risk factors for severe infection were age older than 50 (IRR 3.5; 95%CI 1.42-8.83), obesity (IRR 3.1; 95% CI 1.41-6.87), diabetes (IRR 2.5; 95% CI 1.16-5.50), leukocytosis (IRR 1.03; 95%CI 1.00-1.07) and anemia (IRR 3.0; 95% CI 1.55-5.85). Conclusion Pulmonary Blastomycosis is the most common presentation. Culture and histopathology are more sensitive than antigen assay. Independent factors associated to severe disease were older age, obesity, diabetes, and anemia at admission. Disclosures All Authors: No reported disclosures