Disseminated and Relapsing Cryptococcosis: What We Still Have to Learn—a Case Series and Review of Literature

AbstractTwo cases of disseminated cryptococcosis are described. The first was an HIV-infected patient where cryptococcosis was diagnosed as "unmasking immune reconstitution syndrome"; the second was an immunosuppressed patient with multiple myeloma. In both cases, a definitive healing could not be reached despite long therapeutic approaches. This review summarizes both the most recent and relevant studies about disseminated and refractory form of cryptococcal infections and identifies research gaps. Given the limited data, we draw some conclusions with respect to management from literature: not clear and accepted indication are available regarding disseminated cryptococcosis, no specific schemes were identified, and the duration of therapy is usually decided case by case and supported only by case reports. In this perspective, usually standard therapeutic schemes and duration of induction depend on multiple factors (e.g., neurologic deficit, non-HIV/non transplant status, CSF culture positivity at 2 weeks, etc.). We found that there are no empiric and literature data that support a role of cryptococcal serum antigen (CRAG) in guiding the antifungal therapy; with the data collected, we think that although is possible, it is very rare to find disseminated cryptococcosis with negative CRAG. We looked also for the more important risk factor of recurrence. Some possible causes explored are risk of azole resistant strains, pre-existent conditions of patients that play a permissive role and the common situation where flucytosine is unavailable that led to suboptimal induction phase of therapy. Herein, we discuss disseminated cryptococcosis with a particular attention to antifungal therapy, role of cryptococcal antigen, and risk factors for recurrence of disease

Refractory mucocutaneous leishmaniasis resolved with combination treatment based on intravenous pentamidine, oral azole, aerosolized liposomal amphotericin B, and intralesional meglumine antimoniate

Introduction: Mucocutaneous leishmaniasis (MCL) is a complication of tegumentary leishmaniasis, causing potentially life-threatening lesions in the ear, nose, and throat (ENT) region, and most commonly due to Leishmania (Viannia) braziliensis. We report a case of relapsing MCL in an Italian traveler returning from Argentina. Case description: A 65-year-old Italian male patient with chronic kidney disease, arterial hypertension, prostatic hypertrophy, and type-2 diabetes mellitus was referred for severe relapsing MCL acquired in Argentina. ENT examination showed severe diffuse pharyngolaryngeal edema and erythema, partially obstructing the airways. A nasopharyngeal biopsy revealed a lymphoplasmacytic inflammation and presence of Leishmania amastigotes, subsequently identified as L. (V.) braziliensis by hsp70 PCR-RFLP analysis and sequencing. Despite receiving four courses of liposomal amphotericine B (L-AmB) and two courses of miltefosine over a 2-year period, the patient presented recurrence of symptoms a few months after the end of each course.After the patient was referred to us, a combined treatment was started with intravenous pentamidine 4 mg/kg on alternate days for 10 doses, followed by one dose per week for an additional seven doses, intralesional meglumine antimoniate on the nasal lesion once per week for six doses, oral azoles for three months, and aerosolized L-AmB on alternate days for three months.The treatment led to regression of mucosal lesions and respiratory symptoms. Renal function temporarily worsened, and the addition of insulin was required to maintain glycemic compensation after pentamidine discontinuation. Conclusions: This case highlights the difficulties in managing a life-threatening refractory case of MCL in an Italian traveler with multiple comorbidities. Even though parenteral antimonial derivatives are traditionally considered the treatment of choice for MCL, they are relatively contraindicated in cases of chronic kidney disease.The required dose adjustment in cases of impaired renal function is unknown, therefore the use of alternative drugs is recommended. This case was resolved with combination treatment, including aerosolized L-AmB, which had never been used before for MCL

People with HIV pioneers of injectable cabotegravir and rilpivirine long acting in Italy: who are they?

Injectable cabotegravir and rilpivirine long-acting therapy is a revolutionary new antiretroviral treatment (ART) option for HIV infection in virologically suppressed adults on a stable ART. The aim of this study from SCOLTA multicenter observational prospective database is to describe the first people living with HIV (PWH) who started this regimen in Italy, assessing adherence to eligibility criteria, describing clinical-epidemiological characteristics compared to registration trials-population and describe early treatment-discontinuations