Background Itraconazole is the preferred azole for histoplasmosis in the current Infectious Diseases Society of America guidelines. Voriconazole is increasingly used as treatment for histoplasmosis; it has in-vitro activity against Histoplasma capsulatum and has shown success in case reports and small case series but may have a lower barrier to resistance. No comparative studies have been published. Methods We constructed a single-center retrospective cohort of adult patients diagnosed with histoplasmosis from 2002 to 2017. Individual charts were reviewed to gather clinical information including demographics, clinical features, immune status, treatments, and mortality. Patients were categorized based on initial choice of azole, either as initial treatment or as step-down therapy from amphotericin B. Initial therapies with other azoles were excluded. Mortality was compared using a multivariable Cox proportional hazards with Heaviside function at 42 days. Results We identified 261 cases of histoplasmosis from 2002 to 2017. After excluding patients not treated with itraconazole or voriconazole, 194 patients remained. 175 (90%) patients received itraconazole and 19 (10%) received voriconazole. There were no significant demographic differences between patient populations receiving either azole as their initial azole treatment. Death at 180 days occurred in 41 patients (23.4%) in the itraconazole group and 6 patients (31.6%) in the voriconazole group. Patients on voriconazole had a statistically significant increase in mortality during the first 42 days after initiation of treatment when compared to patients receiving itraconazole (HR 4.30 [95% CI 1.3-13.9, p 0.015]) when controlled for other risk factors. Conclusion Voriconazole in histoplasmosis was associated with increased mortality in the first 42 days compared to itraconazole.

Few large cohorts have examined histoplasmosis in both immunocompromised and immunocompetent patients. We describe the differences in presentations and outcomes of histoplasmosis by immune and dissemination status. We assembled a retrospective cohort of adult patients diagnosed with histoplasmosis from 2002 to 2017. Patients were grouped by immune status: people living with HIV (PLWH), patients who were HIV negative but had other-immunocompromise (OIC), and immunocompetent patients. Patients were further classified into asymptomatic lung nodule (ALN), localized and disseminated disease groups, and outcomes were compared across patients by these immune status categories We identified 261 patients with histoplasmosis: 54 (21%) PLWH, 98 (38%) OIC, and 109 (42%) immunocompetent. Disseminated disease was more common among PLWH than among other groups (P < .001). In localized disease, median time from symptom onset to diagnosis was longer in immunocompetent patients than in other groups (P = .012), and was not significant in disseminated disease. The 90-day mortality was higher in PLWH (25%) and OIC (26%) with localized disease compared to the immunocompetent group (4%) (P = .009), but this difference was not seen in disseminated disease. Patients with localized disease had lower 90-day mortality (14%) compared to those with disseminated disease (21%) (P = .034). We conclude that immunocompetent individuals present with fewer typical symptoms, laboratory findings, and radiographic features of Histoplasma infection, leading to potential delays in diagnosis in this group. Despite this, immunocompetent patients have lower 90-day mortality in localized disease, and do not experience increased 90-day mortality in disseminated disease. Lay Summary This article examines how the signs and symptoms of histoplasmosis vary by immune status and dissemination status. Immunocompetent patients with localized disease present with fewer typical signs and symptoms, are diagnosed later, but despite this have lower 90-day mortality.

Background Histoplasmosis is a common opportunistic infection afflicting people living with HIV (PLWH) globally. There are no data on long term survival of PLWH with histoplasmosis. Methods We conducted a single-center retrospective cohort study of PLWH diagnosed with histoplasmosis between 2002 and 2017. Data collected included demographics, clinical characteristics, treatment, and mortality. Patients were categorized into three groups based on length of survival after diagnosis: early mortality (death within 90 days), late mortality (death at or after 90 days), and survivors. Between group differences in demographic and clinical characteristics were assessed using Chi square for categorical variables and Mann-Whitney U non-parametric tests for continuous variables. Mortality was compared using Cox proportional hazards. Insurance type (i.e. private versus public option) served as a surrogate indicator of socioeconomic status (SES). Patients diagnosed with histoplasmosis in or after 2008 were considered a part of the modern ART era, regardless of treatment regimen. Results Our review found 54 PLWH infected with histoplasmosis from 2002-2017. Overall mortality was 37%, with 14.8% early mortality and 22.2% late mortality. Median survival time in the early mortality group was 13.5 days (IQR 2.5-41 days), and 338 days (IQR 180.5-803.3) in the late mortality group. Compared to the late mortality group, survivors were over 6 times more likely to have suppressed HIV viral load at last observation (HR 6.19, p=0.013). Median HIV viral load at last observation was lower among the survivors (2 log copies/ml, IQR 0, 4.5) compared to the late mortality group (4.1 log copies/ml, IQR 2.6,5.5) (p=0.010). Survivors were twice as likely to have private insurance, but this did not reach statistical significance (HR 2.19, p=0.14). There was no statistically significant difference in survival based on the availability of modern ART (p=0.85). The year of diagnosis made no difference with regards to survival (p=0.914). Baseline Characteristics of PLWH with Histoplasmosis HIV-related Characteristics of PLWH with Histoplasmosis Conclusion Histoplasmosis continues to be associated with high mortality among PLWH. Improved long-term survival is seen in patients with suppressed HIV viral loads. Disclosures Andrej Spec, MD, MSCI, Astellas (Grant/Research Support)Mayne (Consultant)Scynexis (Consultant)

BackgroundThe guideline-preferred azole for histoplasmosis (HP) is itraconazole (IC). While voriconazole (VC) has shown success in in-vitro and in retrospective analyses, there has not been enough data to include newer generation azoles as first-line treatment for infections with Histoplasma capsulatum.MethodsWe conducted a single-center retrospective cohort study of adult patients diagnosed with HP from 2002 through 2017. Data included demographics, clinical features and sites of infection, immune status, treatments, and mortality. Patients were categorized into two groups based on initial choice of azole (IC or VC) and mortality was compared between these two groups. The treatment groups were defined based on the first azole received, either IC or VC, as initial or as step-down therapy from amphotericin. Patients initiated on other azoles were excluded.ResultsWe identified 263 cases of HP from 2002 to 2017. After excluding patients initiated on other azoles, 194 patients remained. 175 (90%) patients were started on IC and 19 (10%) were started on VC, either as stepdown or initial choice of antifungal. There were no significant demographic differences between patients receiving IC compared with VC as their initial azole treatment. Patients with hematologic malignancies tended to be prescribed VC more frequently but this was not statistically significant (OR 3.1 [0.77–12.4]). Death occurred in 40 (23%) patients from the IC and 5 (26%) patients from the VC group. The hazard ratio for mortality with the use of VC was 1.21 (CI 0.4–3.6, P = 0.73).ConclusionIC is the mainstay in the treatment for HP. It appears that VC has comparable outcomes to IC and can be considered an alternative treatment option for HP, at least for patients with contraindications to IC treatment. Disclosures All authors: No reported disclosures.

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