Oseltamivir+Zanamivir combination therapy vs monotherapy for seasonal influenza

A Combination Lock

In infectious diseases, there is always the trade-off between treating the individual patient and the population effects of antimicrobial resistance.  One way to counteract the development of resistance might be combination therapy (eg HIV ART) but this would only apply if the combination provided an added benefit to the individual patient with minimal side effects.  To answer this question for influenza, researchers in France in fall 2009 (85% H3N2 virus) conducted an RCT comparing oral oseltamivir 75 mg twice daily plus zanamivir 10 mg by inhalation twice daily to oral oseltamivir monotherapy or inhaled zanamivir monotherapy. The primary outcome was the proportion of patients with nasal influenza reverse transcription (RT)-PCR below 200 copies genome equivalent (cgeq)/µl at day 2. They also tracked symptom resolution out to day 14 among other outcomes.

The researchers planned to enroll 900 patients with ILI<36 hours and a positive rapid influenza A test, however the RCT was halted after only 541 (447 with confirmed virus) were enrolled.  In the intention to treat analysis, 46% in the O+Z group reached RCT-PCR<200, while this was achieved in 59% of the oseltamivir monotherapy and 34% of the zanamivir monotherapy groups.  Nausea and/or vomiting was more frequent in the combination arm.  Thus, the trial was ended early. The authors concluded: "Despite the theoretical potential for the reduction of the emergence of antiviral resistance, the lower effectiveness of this combination calls for caution in its use in clinical practice."

Duval et al. PLoS Medicine November 2, 2010

Alcohol hand rubs in the workplace: A Randomized Trial

Just a quick post because I've got to get the kids to bed.  Researchers in Germany randomized 134 administrative employees at the Ernst-Moritz-Arndt University Greifswald to alcohol hand rub or nothing (n=67 in each group).  Subjects were to use >3ml of hand rub at least 5x/day especially after using the bathroom, blowing their nose, before eating and after contact with an ill person. The study lasted from March 2005 to April 2006.  People who used hand disinfects prior to the study were excluded.  They found significant reductions in common cold symptoms, fever, cough, and fewer days of illness with each symptom. A thing to note is that 111 of the 134 subjects were female, although it is hard to figure how this would hurt the generalizability. Alright, story time...

BMC Infectious Disease article by Hubner et al.