Treatment options for H5N1: lessons learned from the H1N1 pandemic.

Human infections with avian influenza A (H5N1) are relatively rare but are associated with high mortality. As of July 5, 2010 there had been 500 cases and 296 fatalities. The influenza virus readily undergoes mutation and reassortment, and there are concerns that an H5N1 variant could be responsible for a future pandemic.

Zanamivir for the treatment of avian influenza infections in humans.

Zanamivir is currently not recommended by the WHO for the first-line treatment of human influenza A (H5N1) infections. Zanamivir pharmacokinetics and antiviral efficacy were reviewed to assess the basis for this recommendation. Following inhalation of 10 mg zanamivir in healthy humans, the drug is widely distributed throughout the lungs.

Necrotizing otitis externa: a painless reminder.

Necrotizing otitis externa is a necrotizing osteomyelitis of the skull base that predominantly affects diabetic and immunocompromised patients. Pseudomonas aeruginosa is the most frequently implicated organism. Patients present with severe otalgia, otorrhoea with or without facial palsy, or rarely, facial pain as a symptomatic feature.

Neuraminidase inhibitor resistance in influenza viruses.

Zanamivir and oseltamivir, the currently marketed influenza virus neuraminidase inhibitors (NAIs), are prescribed for the treatment and prophylaxis of influenza and are being stockpiled for pandemic influenza. Oseltamivir resistance has been reported in up to 2% of patients in clinical trials of oseltamivir and in up to 18% of treated children. There are also reports in at least three patients treated with oseltamivir for influenza A (H5N1) infections.

Potent and long-acting dimeric inhibitors of influenza virus neuraminidase are effective at a once-weekly dosing regimen.

Dimeric derivatives (compounds 7 to 9) of the influenza virus neuraminidase inhibitor zanamivir (compound 2), which have linking groups of 14 to 18 atoms in length, are approximately 100-fold more potent inhibitors of influenza virus replication in vitro and in vivo than zanamivir. The observed optimum linker length of 18 to 22 A, together with observations that the dimers cause aggregation of isolated neuraminidase tetramers and whole virus, indicate that the dimers benefit from multivalent binding via intertetramer and intervirion linkages. The outstanding long-lasting protective activities shown by compounds 8 and 9 in mouse influenza infectivity experiments and the extremely long residence times observed in the lungs of rats suggest that a single low dose of a dimer would provide effective treatment and prophylaxis for influenza virus infections.

An orally bioavailable oxime ether capsid binder with potent activity against human rhinovirus.

A series of capsid-binding compounds was screened against human rhinovirus (HRV) using a CPE based assay. The ethyl oxime ether 14 was found to have outstanding anti-HRV activity (median IC(50) 4.75 ng/mL), and unlike the equivalent ethyl ester compound 3 (Pirodavir), it has good oral bioavailability, making it a promising development candidate.