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Multiple-drug resistance: case report A 72-year-old man developed multiple-drug resistance during treatment with oseltamivir and zanamivir for influenza-A virus (H1N1) infection [not all routes and dosages stated]. The man had history of acute myeloid leukaemia. On 6 December 2017, he underwent an allogenic haematopoietic stem cell transplant (HSCT). On 22 January 2018, he was hospitalised for suspected intestinal graft versus host disease (GvHD). Five days after admission, he developed influenza-like symptoms and subsequently, his nasopharyngeal swabs (NPS), was positive for influenza A (H1N1) pdm09 virus. Thus, on 28 January 2018, he was initiated on oseltamivir 150mg twice daily. On 12 February 2018, despite viral positivity collected on an NPS, oseltamivir was discontinued on 14 February 2018, due to further decline in renal function. However, his oxygen saturation subsequently decreased again. An NPS was collected and oseltamivir was re-started on 27 February 2018 with dosage adapted to a decreased GFR. In the absence of clinical improvement, oseltamivir was replaced with IV zanamivir on 1 March 2018. While subsequent NPS samples initially suggested a decrease in viral load, but influenza A RT-PCR cycle threshold (Ct) values dropped again after 12 March 2018, despite continuous zanamivir treatment. After, clinical improvement zanamivir was therefore stopped. A chest CT scan, on 20 March 2018, revealed an increase in bronchiectasis, indicating fibrosing process. On 20 April 2018, he developed respiratory deterioration. Thus, zanamivir was restarted on 20 April 2018, but; due to a rapid clinical improvement upon unspecified broad spectrum antibiotic treatment initiation, antiviral treatment with zanamivir was stopped after 3 days. Thereafter, he developed dyspnoea again and his condition deteriorated, particularly at the respiratory level. Unfortunately, he died on 23 May 2018. Autopsy was performed which revealed multiple pneumonia foci, of different ages, with active abscess forming pneumonia, organizing pneumonia foci and constituted fibrosis. Viral gene sequencing (HA/NA genes) revealed mutations. Thus, it was determined that oseltamivir rapidly induced the H275Y NA mutation after 15 days of oseltamivir treatment, and after a switch to zanamivir, 275H/Y and 119E/G/D mixed populations were also detected resulting in development of multiple-drug resistance to oseltamivir and zanamivir. Abed Y, et al. Molecular pathway of influenza pan-neuraminidase inhibitor resistance in an immunocompromised patient. Antiviral Therapy 24: 581-587, No. 8, 2019. 803517812 Available from: URL: http://doi.org/10.3851/IMP3344

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Reactions 28 Nov 2020 No. 1832