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The 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) was held this week in Denver Colorado, and once again we’re fortunate to have videos of press conferences being webcast live and archived via MicrobeWorld’s Youtube channel.
Two interviews of particular interest to Flublogia concern research on the use of Triple-dose Oseltamivir (Tamiflu ®) on critically ill patients during the 2009 pandemic, and research looking at using alpha-Interferon for the treatment of H7N9.
The standard adult dose of Tamiflu for uncomplicated seasonal influenza is 75mg, twice a day for 5 days – although higher doses over longer periods of time have been proposed (and even tried) when dealing with avian or severe pandemic flu.
Last May, in Delving Into The Oseltamivir Dosage Study, we looked at a BMJ study that found No benefit of double dose antiviral drug for severe influenza. This study, however, had a number of limitations:
- Most of the patients were children under 15
- Most of the patients had low or normal BMI
- Only about 1/5th had underlying conditions
- Very few adults were included in the study
- Only 17 (of 326 cases) were H5N1, and of those, only 3 survived to day 5 of the trial.
- The average delay for treatment for H5N1 patients was 7 days vs. 5 days for seasonal flu
- All H5N1 cases met the criteria for clinical failure
One is left to wonder how well these results would translate to a much older population, one likely to have a higher average BMI, far more (and different) underlying conditions, and in all likelihood would seek treatment sooner than did the patients in this study (average 5-7 days).
While this trial found no value to doubling the dose for seasonal flu, there is insufficient evidence to judge whether doubling the dose for H5N1 (or presumably H7N9) would improve patient survival. And in an accompanying editorial, Ian Barr and Aeron Hurt of the WHO Collaborating Centre for Reference and Research on Influenza, would appear to agree:
What is clear is that double dose oseltamivir is unlikely to significantly improve the clinical outcomes of severe cases of seasonal influenza, although there were probably insufficient data to determine if this was also true for people infected with A(H5N1).
It is worth noting that last April, in CDC Interim Guidance On H7N9 Antiviral Treatment, we saw the CDC’s recommendation that for hospitalized patients:
The optimal duration and dose of therapy are uncertain in severe or complicated influenza. Pending further data, longer courses of treatment (e.g., 10 days of treatment) should be considered for severely ill hospitalized H7N9 patients.
Earlier this summer, we looked at the general effectiveness of oseltamivir, and the need for maintaining stockpiles in New Scientist: Don’t Stop Stockpiling Tamiflu.
All of which brings us to the first ICAAC video:
High Dose Therapy for Influenza Drug - Watch Now
Critically ill patients with the pandemic H1N1 influenza who received triple the standard dose of the influenza drug oseltamivir were 7 times more likely to completely clear the virus from their system in 5 days than those who received the standard dose. This discussion will address the healthcare implications of these findings, including a rationale for high dose therapy of sensitive strains of influenza.
- Anand Kumar, Hlth. Sci. Ctr., Winnipeg, MB, Canada
Dr. Kumar reports that the triple dose of Tamiflu was well tolerated, and believes higher doses may be appropriate for those severely ill from influenza. For more on the topic of antivirals, and their use for pandemic or avian flu, you may wish to revisit Study: Antiviral Therapy For H5N1 and Hong Kong Finds Success With Higher Tamiflu Doses.
Our next stop is an interview with William M. Mitchell, Vanderbilt University, Nashville, TN who discusses the use of interferon Alpha as a possible treatment of oseltamivir-resistant H7N9. You may recall that just last week, in Nature: Animal Testing Of Drug Combo Shows Potential For Treating MERS Interferon was also proposed as part of a cocktail to potentially treat the MERS Coronavirus.
According to a press release yesterday from Hemispherx Biopharma, Inc, their findings are based on in vitro experiments, directed against inhibiting the replication of two strains of H7N9 virus in A549 cell lines. One H7N9 strain (A/Anhui/1/2013) was a `wild type’ that was susceptible to oseltamivir, while the other (A/Shanghai/1/2013) was a patient isolate that had developed Tamiflu resistance.
Dr. Mitchell describes the suppression of the wild-type virus as being roughly equal with both oseltamivir and interferon, but the resistant strain (which greatly thwarted the antivirals) showed an even greater response to interferon alpha.
The caveat here is, these are in vitro experiments. Clinical trials have not been conducted, but these are promising – if very early – results. Mitchell suggests that if the need arose during a pandemic outbreak, an Emergency Use Authorization (EUA) might be issued.
In the following ICAAC video Dr. Mitchell discusses this research and the potential of using interferon-alpha as a treatment for severe influenza. Note: Mitchell is a board member and shareholder of Hemispherx Biopharma of Philadelphia, which supported this research.
Human Interferon Kills Resistant H7N9 Influenza - Watch Now
During the April 2013 avian influenza A (H7N9) outbreak, more than 130 human infections with H7N9 were reported. Most patients had severe respiratory illness and 44 people have died. Studies suggest that the H7N9 virus has developed resistance to oseltamivir. A human interferon already in use for treatment of genital warts, alpha-n3, has been found to be active against the virus, even the oseltamivir-resistant isolate. Participants will discuss these findings and implications.
You’ll find more videos from this year’s ICAAC on this page, and many more offerings from the American Society for Microbiology Youtube Channel.
