In Vitro Characterization of Multidrug-Resistant Influenza A(H1N1)pdm09 Viruses Carrying a Dual Neuraminidase Mutation Isolated from Immunocompromised Patients.
Emi TakashitaSeiichiro FujisakiMasaru YokoyamaMasayuki ShirakuraHiroko MoritaKazuya NakamuraNoriko KishidaTomoko KuwaharaHironori SatoIkuko DoiYuji SatoShinichi TakaoYukie ShimazuTakeshi ShimomuraTakuo ItoShinji WatanabeTakato Odagirinull The Influenza Virus Surveillance Group Of JapanPublished in: Pathogens (Basel, Switzerland) (2020)
Influenza A(H1N1)pdm09 viruses carrying a dual neuraminidase (NA) substitution were isolated from immunocompromised patients after administration of one or more NA inhibitors. These mutant viruses possessed an H275Y/I223R, H275Y/I223K, or H275Y/G147R substitution in their NA and showed enhanced cross-resistance to oseltamivir and peramivir and reduced susceptibility to zanamivir compared to single H275Y mutant viruses. Baloxavir could be a treatment option against the multidrug-resistant viruses because these dual H275Y mutant viruses showed susceptibility to this drug. The G147R substitution appears to stabilize the NA structure, with the fitness of the H275Y/G147R mutant virus being similar or somewhat better than that of the wild-type virus. Since the multidrug-resistant viruses may be able to transmit between humans, surveillance of these viruses must continue to improve clinical management and to protect public health.
Keyphrases
- multidrug resistant
- wild type
- public health
- end stage renal disease
- chronic kidney disease
- ejection fraction
- drug resistant
- genetic diversity
- gram negative
- acinetobacter baumannii
- prognostic factors
- peritoneal dialysis
- patient reported outcomes
- cystic fibrosis
- intensive care unit
- extracorporeal membrane oxygenation