The disease caused by the new SARS-CoV-2, known as Coronavirus disease 2019 (COVID-19), was first identified in China in December 2019 and rapidly spread around the world. Coinfections with fungal pathogens in patients with COVID-19 add challenges to patient care. We conducted a literature review on fungal coinfections in patients with COVID-19. We describe a report of a patient with disseminated histoplasmosis who was likely infected with SARS-CoV-2 and experienced COVID-19 during hospital care in Buenos Aires, Argentina. This patient presented with advanced HIV disease, a well-known factor for disseminated histoplasmosis; on the other hand, we suspected that COVID-19 was acquired during hospitalization but there is not enough evidence to support this hypothesis. Clinical correlation and the use of specific Histoplasma and COVID-19 rapid diagnostics assays were key to the timely diagnosis of both infections, permitting appropriate treatment and patient care.
Introduction:Cryptococcosis is an opportunistic mycosis, especially in patients that are human immunodefi ciency virus (HIV)-positive, and frequently involves the central nervous system. Methods: We assessed the potential of ventriculoperitoneal shunting (VPS) in preventing mortality due to uncontrollable intracranial hypertension (ICH) in 15 patients with acquired immunodefi ciency syndrome (AIDS)-related cryptococcal meningitis. Results: After 2 weeks of antifungal therapy consisting of amphotericin B deoxycholate with or without fl uconazole, patients with persistent ICH underwent VPS, despite having persistent Cryptococcus neoformans infection. In 12 patients, the uncontrollable ICH was resolved by VPS. Conclusions: Patients with cryptococcal meningoencephalitis who have ICH must be considered for VPS even with positive cerebrospinal fl uid cultures.
Background
Chagas disease reactivation in HIV positive people is an opportunistic infection with 79–100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data is available, especially its concentration in CNS.
Methods
We report a series of HIV positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. An HPLC-MS/MS bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples.
Results
Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only 3 of the CSF samples had detectable BNZ levels, all under 1 μg/mL. Although this, 15 plasma samples had detectable BNZ, and 13 were above 2 μg/mL, which is the putative trypanocidal level.
Conclusions
We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or non-measurable in all patients, suggesting that usual BNZ doses may be suboptimal in HIV positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. The findings highlight the potential of therapeutic drug monitoring in BNZ treatment, and suggest that use of higher doses may be useful for Chagas disease CNS reactivations.
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