Stewardship / Resistance Scan for Feb 08, 2017

News brief

Chinese study finds increasing rate of MCR-1 carriage in humans

A new study out of China indicates that human fecal carriage of MCR-1-positive, multidrug-resistant Enterobacteriaceae is on the rise.

For the study, posted yesterday on the preprint server bioRxiv, Chinese investigators tested 8,022 human fecal samples collected from three hospitals in Guangdong from April 2011 through March 2016. They were looking for the presence of the MCR-1 gene, which was first identified in Escherichia coli samples from pigs, pork products, and humans in China in 2015.

MCR-1 has since become a major health concern because it confers resistance to colistin, a last-resort antibiotic used in the treatment of multidrug-resistant infections. An additional concern is the co-existence of the gene, which is carried on mobile pieces of DNA called plasmids, with other resistance mechanisms.

Of the 8,022 fecal samples, the investigators found that 497 (6.2%) were MCR-1 positive, and 182 (2.3%) were MCR-1 positive and resistant to cefotaxime, a broad-spectrum cephalosporin. From the fecal samples harboring MCR-1-positive/cefotaxime-resistant Enterobacteriaceae, the team identified 187 distinct Enterobacteriaceae isolates from 179 individuals. The vast majority of the isolates (173) were Escherichia coli.

The rate of MCR-1 gastrointestinal carriage noted in the study is significantly higher than previous studies have found. The investigators also found that the MCR-1-positive and MCR-1-positive/cefotaxime-resistant samples increased significantly over the 5 years of the study, with a specific increase after January 2014. In addition, genetic analysis showed that the MCR-1 gene is spreading through a diverse set of genetic mechanisms (including strains, plasmids, and insertion sequences) that are helping contribute to its dissemination and could help facilitate its persistence.

"Our genetic analyses suggest the rapid emergence of several major plasmid vectors of mcr-1 within numerous multidrug-resistant E. coli strains carried by humans, and highlight the significant degree of plasticity in these plasmid vectors harbouring mcr-1 over short periods of time," the authors write.

The study has not yet been peer-reviewed.
Feb 8 bioRxiv abstract

Report notes high levels of highly resistant Acinetobacter in Nepal

Almost all isolates of Acinetobacter baumannii in Nepal were found to be resistant to multiple antibiotics, according to a small study yesterday in Antimicrobial Resistance & Infection Control.

Nepalese researchers analyzed 44 isolates of A baumannii, an increasingly important pathogen. The found that 43 (98%) were resistant to carbapenems, an important tool for combating antibiotic-resistant bacteria. The same number of isolates were multidrug resistant, but all were susceptible to colistin. The bla-OXA-23 gene was detected in all of the isolates, while the New Delhi Metallo-beta-lactamase-1 (NDM-1) gene was identified in 6 (14%).

The authors conclude, "Systemic network surveillance should be established for monitoring and controlling the spread of these resistant strains."
Feb 7 Antimicrob Resist Infect Control study

Study: Standard pasteurization kills Ebola virus in breast milk

A recent study in the Journal of Human Lactation showed that pasteurizing breast milk kills both Ebola and Marburg viruses. The research was done at the Mother's Milk Bank of North Texas (MMBNT), and was conducted in the wake of the 2013-2016 Ebola outbreak.

Earlier reports have described infectious Ebola virus in human milk 15 days after illness onset and viral RNA as late as 26 days after symptoms begin.

Authors of the study inoculated donor breast milk with both Ebola and Marburg viruses, then subjected the milk to Holder pasteurization, the standard treatment at milk banks. During Holder pasteurization, donor milk is heated for 30 minutes in a water bath held at 62.5º Celsius.

The researchers found no traces of either virus in the pasteurized milk, and said there is no need for Ebola virus screening at milk banks. This is the first published study on these viruses and heat pasteurization.

"Although the presence of Ebola in a breastfeeding mother would be extremely unlikely, safety for the fragile babies we serve is our top priority and we know that as a body fluid, breast milk is vulnerable," said AmyVickers, executive director of MMBNT in a press statement.
Feb 7 MMBNT press release
Jan 30 J Hum Lact
study

 

Droughts increase severity of West Nile Virus epidemics

Drought, more than precipitation levels or winter temperatures, is an influential driver behind West Nile virus (WNV) outbreaks, according to a study today in the Proceedings of the Royal Society Biological Sciences.

Though climate change has long been implicated in WNV, this is the first study to show that drought changes the ecological hosts and vectors that can spread WNV. Using daily minimum and maximum temperature and precipitation data from 1999 to 2013 in the National Centers for Environmental Prediction North American Regional Reanalysis (NARR), and mosquito collection data from 2003 to 2008 in 15 counties in Colorado, the authors of the study presented models that predict increasing incidence of WNV over the next 30 years.

"We found that the primary drivers of interannual variation in WNV across the USA include drought and immunity, and that increases in drought could potentially double WNV epidemic intensity nationally," the authors write. "The positive relationship between drought and WNV infection prevalence in Colorado mosquitoes suggests that drought alters transmission in this state not by reducing mosquito abundance, but by increasing infection prevalence."

North America had its first case of WNV in 1999, and since then has seen the vector-borne disease increase, especially in drought-prone states, such as Colorado.
Feb 8 Proc Royal Soc B study

 

No new safety concerns with second dose of varicella vaccine

In 2006, the American Academy of Pediatrics recommended a two-dose routine varicella vaccine to protect more children against infection with chicken pox. Now, a Centers for Disease Control and Prevention study published yesterday in Pediatrics confirms that the second dose of the vaccine is safe and poses no new safety concerns for recipients.

The study was conducted by reviewing reports made to the Vaccine Adverse Event Reporting System from 2006 to 2014. Second-dose varicella dose adverse events (AEs) among children ages 4 to 6 and 7 to 18 were reviewed.  Of the 14,641 AEs reported, only 3% (494) were classified as serious, including 7 deaths, 5 cases of meningitis, 6 cases of varicella, and 83 cases of anaphylaxis.

The most common nonserious AEs were injection site reactions (48% of children aged 4 to 6 years, 38% of children aged 7 to 18 years), headache (28%) and vomiting (27%).

The authors of the study called the results "reassuring" and said there were no new or unexpected safety concerns from the 2-dose varicella vaccine.
Feb 7 Pediatrics study

 

Study finds some downside to multiple-year vaccination against H1N1 flu

A case-control study that included four seasons' worth of data in Spain found only a small effect of previous-year vaccination lowering the vaccine effectiveness (VE) of flu immunization regarding the 2009 H1N1 strain, with a 46% VE over the seasons against that strain, according to a study yesterday in the Journal of Infectious Diseases.

Spanish researchers enrolled 1,278 patients with lab-confirmed H1N1 flu and 2,343 controls from 2010-11 to 2015-16 and used a test-negative design. They included data only from the four seasons that had at least 20 confirmed H1N1 cases.

When analyzing season-specific data, the investigators found no significant differences in flu VE between those vaccinated in only the current season and those who had also been vaccinated before. They noted VE of 66% in those who had received one or two previous doses, 47% in those who had received more than two doses, and 52% in those who were vaccinated but had received no previous doses, but these differences were not statistically significant.

In pooled analyses using all the data, however, the team determined that VE was lower among those with two or more previous-season doses. VE was 66% in those with one to two previous doses, 52% in those with no previous doses, and 37% in those with more than two doses. The pooled data also revealed an overall VE of 46%.

An accompanying commentary lauds the mostly positive results, but points out that that the flu vaccine does not stand up as well against the H3N2, which is predominant this season and is typically associated with greater illness severity.
Feb 7 J Infect Dis study
Feb 7 J Infect Dis commentary

 

New framework shows oseltamivir cost-effective for pandemic flu

An analysis that factored in pharmacologic parameters alongside epidemiologic and economic measures found that oseltamivir (Tamiflu) is cost-effective for preventing infections and deaths in most pandemic scenarios. An international team published its findings today in the British Journal of Clinical Pharmacology.

There's a growing need to justify drug costs to payers, but earlier mathematical model studies designed to help guide pandemic planning haven't considered basic antiviral pharmacology features and how they link to epidemiologic and economic end points, the researchers said. For their new analysis, they factored in pharmacokinetic and pharmacodynamics data from phase 2 clinical trials and information on disease spread from an earlier flu outbreak.

Compared with no treatment, the standard 5-day 75-milligram (mg) twice-daily dose regimen was effective and affordable in all pandemic flu scenarios. It reduced the number of infected people, increased quality-adjusted life years by deaths averted, and was cost saving. When the experts compared the standard regimen with higher-dose treatment (150 mg twice daily), the regimen was cost saving in high-transmissibility but not low-transmissibility scenarios.

Craig Rayner, PharmD, MBA, chief executive officer with d3 Medicine and one of the study coauthors, said in a press release from Wiley, the journal's publisher, "This approach—which we have called 'pharmacology to the payer'—can be applied across all disease areas and should facilitate greater dialogue between industry, regulators, payers, and patients earlier in the drug development process."
Feb 8 Br J Clin Pharmacol abstract
Feb 8 Wiley press release

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