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.

Histoplasmosis is a common opportunistic infection in people with HIV (PWH); however, no study has looked at factors associated with the long-term mortality of histoplasmosis in PWH. We conducted a single-center retrospective study on the long-term mortality of PWH diagnosed with histoplasmosis between 2002 and 2017. Patients were categorized into three groups based on length of survival after diagnosis: early mortality (death < 90 days), late mortality (death ≥ 90 days), and long-term survivors. Patients diagnosed during or after 2008 were considered part of the modern antiretroviral therapy (ART) era. Insurance type (private vs. public) was a surrogate indicator of socioeconomic status. Out of 54 PWH infected with histoplasmosis, overall mortality was 37%; 14.8% early mortality and 22.2% late mortality. There was no statistically significant difference in survival based on the availability of modern ART (p = 0.60). Insurance status reached statistical significance with 38% of survivors having private insurance versus only 8% having private insurance in the late mortality group (p = 0.05). High mortality persists despite the advent of modern ART, implicating a contribution from social determinants of health, such as private insurance. Larger studies are needed to elucidate the role of these factors in the mortality of PWH.

Antibiotics have been extensively used in COVID-19 patients without a clear indication. We conducted a study to evaluate the feasibility of procalcitonin along with the “Clinical Pulmonary for Infection Score” (CPIS) as a strategy to reduce inappropriate antibiotic use. Using procalcitonin and CPIS score (PCT-CPIS) successfully reduced inappropriate antibiotics use among severe-critically ill COVID-19 pneumonia patients (45% vs. 100%; p<0.01). Compared to “non PCT-CPIS” group, “PCT-CPIS” group was associated with a reduction in the incidence of multidrug-resistant organisms and invasive fungal infections (18.3% vs. 36.7%; p=0.03), shorter antibiotic duration (2 days vs 7 days; p<0.01) and length of hospital stay (10 days vs. 16 days; p<0.01).

We report a case of Nocardia farcinica ruptured intracranial mycotic aneurysm associated with bortezomib and corticosteroid treatment in a multiple myeloma patient. The patient was treated with trimethoprim-sulfamethoxazole and moxifloxacin together with surgical repairment of intracranial mycotic aneurysm.