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Norepinephrine/oseltamivir Lack of efficacy and invasive pulmonary aspergillosis secondary to off-label use: case report

A 71-year-old man developed invasive pulmonary aspergillosis during off-label treatment with oseltamivir for COVID-19, and exhibited lack of efficacy during treatment with norepinephrine for haemodynamic instability [duration of treatment to reaction onset and outcome not stated; not all routes stated]. The man, who had a history of type II diabetes mellitus, chronic kidney disease and hypertension, was hospitalised to the Hospital e Pronto-Socorro Delphina Rinaldi Abdel Aziz, Brazil with cold extremities and cyanosis. He was transferred from another hospital, where he had already been diagnosed with COVID-19. On admission in the ICU, he was placed under orotracheal intubation and was treated with unspecified vasoactive drugs. He was haemodynamically unstable. Hence, he was treated with norepinephrine 1.41 µg/kg/min and placed on mechanical ventilation. The partial pressure of arterial oxygen/percentage of inspired oxygen (PaO2/ FiO2 ratio) was 86.6. He received off-label treatment with chloroquine 450mg twice on the first day and oseltamivir 75mg twice daily via a nasoenteral tube, IV ceftriaxone 2 g/day, IV furosemide 20mg three times daily and IV azithromycin 500 mg/day along with prophylactic enoxaparin sodium [enoxaparin]. Laboratory tests revealed elevated urea level 360.7 mg/dL, creatinine 8.46 mg/dL, CRP 12 mg/L, leucocyte count 6530 /µL, Hb level 11.2 g/dL, platelet count 285 x 109 /µL, haematocrit 34.5%, lymphopenia 12.8% and neutrophilia 84%. Chest X-ray revealed nodular and infiltrate consolidation in the right lower lobe. On hospitalisation day 3, his condition progressed with haemodynamic worsening and refractory shock, with bradycardia and irreversible hypotension. The following day, he died due to refractory shock, bradycardia and irreversible hypotension. An autopsy was performed. Macroscopic visualisation of the lung revealed focal areas of consolidation in the right lower lobe. Microscopic visualisation of the lung revealed the presence of Aspergillus structures, including fungal spores and hyphae, and Aspergillus head with phialides, conidia, and spores, as well as fibrin thrombi occluding an artery, bronchopneumonia, and squamous metaplasia. The peripheral blood tested positive for the galactomannan antigen (index 4.290). A diagnosis of invasive pulmonary aspergillosis secondary to oseltamivir was made. The nucleotide sequencing confirmed the Aspergillus spp. Santana MF, et al. Confirmed invasive pulmonary aspergillosis and COVID-19: The value of postmortem findings to support antemortem management. Revista da Sociedade 803498704 Brasileira de Medicina Tropical 53: 1-4, Jan 2020. Available from: URL: http://doi.org/10.1590/0037-8682-0401-2020

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Reactions 29 Aug 2020 No. 1819