Stewardship / Resistance Scan for Jan 20, 2017

Antiviral-resistant H1N1 flu
Fecal transplants for C diff

Investigation shows multi-antiviral-resistant H1N1 flu

A case report on an immunocompromised patient with prolonged influenza virus in yesterday's Eurosurveillance reveals resistance to two common antiviral drugs and shows how rapidly antiviral resistance can evolve, a finding the authors say highlights the importance of rapid antiviral resistance testing.

The report involved a Danish man with chronic lymphocytic leukemia who had prolonged shedding of 2009 H1N1 influenza A virus for 6 months and was treated with the antivirals oseltamivir (Tamiflu) and zanamivir (Relenza). Investigation of respiratory samples using Sanger sequencing and next-generation sequencing showed that resistance to oseltamivir, caused by resistance mutation H275Y, was detected 15 days after the end of the first treatment with the antiviral and likely limited the effect of the second treatment.

On day 96 of the treatment, 1 week after the patient had begun inhalation therapy with zanamivir and 3 months after onset of symptoms, respiratory samples contained virus with the H275Y mutation and an additional S247N mutation. By day 149, when the patient had almost completed the second zanamivir treatment, genetic sequencing detected the H257Y, I233R, and E119G mutations, along with two additional mutations, showing a more complex viral population in the patient and resistance to zanamivir as well as oseltamivir.

"The rapidly evolving antiviral resistance observed in this case," the authors write, "emphasises the importance of timely antiviral resistance testing during treatment of influenza virus infection in order to change treatment regime and avoid unnecessary administration of ineffective medicaments, as well as preventing spread of antiviral resistant viruses."
Jan 19 Eurosurveill research article


Fecal transplant via enema found to be most cost effective for C diff

A French analysis of five different strategies for the treatment of recurrent Clostridium difficile infection (CDI) indicates that fecal microbiota transplantation (FMT) via enema is the most cost effective, according to a study yesterday in PLoS One.

CDI is the leading cause of healthcare-associated diarrhea, and incidence and severity have been on the rise in North America and Europe in recent years.  Recurrent infections are also a problem, the authors of the study explain, with the risk of recurrent CDI in patients who have already had one recurrence rising from 25% after an initial episode to 45% after a first recurrence and to 65% after two recurrences.

Using a decision-analytic simulation model, the French researchers set out to compare five treatments for the management of second recurrence of community-onset CDI: (1) pulse-tapered vancomycin (the current standard approach), (2) fidaxomicin, (3) FMT via colonoscopy, (4) FMT via duodenal infusion, (5) and FMT via enema. The model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), and ICERs were interpreted using a willingness-to-pay threshold of €32,000/QALY ($34,226/QALY).

The decision model indicated that while pulse-tapered vancomycin was less costly than FMT, FMT in all modes of delivery was more effective. FMT via colonoscopy and FMT via enema were both more effective than pulse-tapered vancomycin, but FMT via enema was the less expensive option. The extra cost for FMT via enema for increased effectiveness compared with vancomycin was €18,092/QALY ($19,356/QALY), while the extra cost for FMT via colonoscopy compared with FMT via enema was €73,653/QALY ($78,798/QALY).

"Thus, FMT via enema appears to be the most cost-effective strategy at a willingness to pay threshold of €32,000/QALY," the authors write.
Jan 19 PLoS One study

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