RESUMO
The circulation of avian influenza A viruses in poultry is a public health concern due to the potential transmissibility and severity of these viral infections. Monitoring the susceptibility of these viruses to antivirals is important for developing measures to strengthen the level of preparedness against influenza pandemics. However, drug susceptibility information on these viruses is limited. Here, we determined the susceptibilities of avian influenza A(H5N1), A(H5N2), A(H5N8), A(H7N7), A(H7N9), A(H9N1), and A(H9N2) viruses isolated in Japan to the antivirals approved for use there: an M2 inhibitor (amantadine), neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, and laninamivir) and RNA polymerase inhibitors (baloxavir and favipiravir). Genotypic methods that detect amino acid substitutions associated with antiviral resistance and phenotypic methods that assess phenotypic viral susceptibility to drugs have revealed that these avian influenza A viruses are susceptible to neuraminidase and RNA polymerase inhibitors. These results suggest that neuraminidase and RNA polymerase inhibitors currently approved in Japan could be a treatment option against influenza A virus infections in humans.
Assuntos
Farmacorresistência Viral , Influenza Aviária , Influenza Humana , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , RNA Polimerases Dirigidas por DNA , Farmacorresistência Viral/genética , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Virus da Influenza A Subtipo H5N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H5N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H7N7/efeitos dos fármacos , Subtipo H7N9 do Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A Subtipo H9N2/efeitos dos fármacos , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Japão/epidemiologia , Neuraminidase/genética , Neuraminidase/metabolismo , Oseltamivir/farmacologia , Oseltamivir/uso terapêutico , Aves DomésticasRESUMO
The emergence of fluoroquinolone-resistant strains of Salmonella enterica subspecies enterica serovar Choleraesuis is an important concern in several countries, including Japan. We examined the intracellular concentration of enrofloxacin in S. Choleraesuis to determine the existence of a relationship with the emergence of quinolone resistance. The intracellular concentration of enrofloxacin was significantly lower in nalidixic acid-resistant isolates compared with nalidixic acid-susceptible isolates. In the presence of carbonyl cyanide m-chlorophenylhydrazone, the intracellular concentration of enrofloxacin increased in all isolates, with no significant difference in the intracellular concentration between nalidixic acid-susceptible and -resistant isolates. The frequency of emergence of fluoroquinolone-resistant mutants was higher in susceptible isolates with a low intracellular concentration of enrofloxacin. The results presented suggest that a decrease in the intracellular concentration of enrofloxacin is related to active efflux pumps and contributes to the emergence of fluoroquinolone resistance.
