Stewardship / Resistance Scan for Feb 20, 2018

News brief

CARB-X announces first award for 2018, two more funding rounds

CARB-X, a public-private collaboration that supports companies in early-stage antibiotic discovery and development, recently announced its first funding award for 2018 and provided details about two funding rounds for the current year.

CARB-X said in a Feb 15 announcement that it is funding Curza, based in Salt Lake City, to support the development of a new class of antibiotics to treat a broad spectrum of life-threatening gram-negative bacteria that are resistant to currently available antibiotics. Curza's initial award is worth up to $2.2 million, with the possibility of $1.8 million more if it achieves certain milestones.

Kevin Outterson, JD, executive director of CARB-X, said in a statement from the group, "Curza's new class of antibiotics is an exciting addition to the Powered by CARB-X portfolio as it has been decades since the last new class was approved to for gram-negative bacteria." Curza's CZ-02 series is designed to kill bacteria with known resistance to other ribosomal antibiotics by binding to a clinically undrugged and highly conserved site on the bacterial ribosome.

The drugs have a unique mechanism that maximizes penetration of bacterial cells that leads to potent activity against drug-resistant ESKAPE pathogens, which include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species.

In another CARB-X development, the group today announced two funding rounds, one open from Mar 22 through Mar 29, targeting new classes of direct-acting small-molecule and large-molecule antibacterials that target certain gram-negative bacteria. The second round is open from Jun 1 through Jun 8 and includes direct-acting therapies and a broader scope of vaccines, drugs, diagnostics, and devices that meet certain criteria.

Outterson said, "The scope of each funding cycle has been carefully designed to meet the most urgent needs in the global pipeline to treat drug-resistant bacterial infections and respond to the rising threat of drug resistant bacteria."
Feb 15 CARB-X press release
Feb 20 CARB-X press release

MRSA bacteremia rates higher in states with more African-Americans

A new analysis of hospital-onset methicillin-resistant Staphylococcus aureus bacteremia (HO-MRSAB) rates suggests that states with more African-American residents have higher incidence, researchers reported yesterday in Infection Control and Hospital Epidemiology.

In the study, researchers looked at state-level HO-MRSAB data for the year 2013 obtained from the Centers for Disease Control and Prevention and at census-derived demographic and socioeconomic variables. Although variations in HO-MRSAB rates among states have been explained by differences in the quality of infection-control practices, the researchers wanted to evaluate whether risk factors that have been well-studied at the individual level (including race, age, gender, and diabetic status) affect variations among populations.

Univariate analysis demonstrated significant positive correlations between HO-MRSAB rates and poverty rates, income inequality, percent of the population with diabetes, and the percent of the population that self-identify as African-American. But on multivariable analysis, the researchers found that African-American identity was the only variable that retained statistical significance.

While acknowledging that the findings suggest only a correlation and require further investigation, the authors of the study say that identifying population-level risk factors for HO-MRSAB is the first step toward developing risk-adjustment tools that would allow for more meaningful comparisons among states and more accurate estimates of the contribution of infection-control practices.
Feb 19 Infect Control Hosp Epidemiol abstract

FAO warns about antimicrobial resistance in Asia-Pacific

Diseases originating in animals (called zoonotic diseases) and antimicrobial resistance (AMR) are converging in Asia-Pacific nations and threatening human health, the United Nations Food and Agriculture Organization (FAO) Regional Office for Asia and the Pacific warned today.

"We need to take action on AMR now because it affects us all," Juan Lubroth, DVM, FAO's chief veterinarian and AMR coordinator, said in an FAO news release. He added that antimicrobial overuse and misuse in humans and animals are resulting in the spread of AMR, which is complicating the treatment of many infectious diseases.

"Antibiotics and other antimicrobials are vital to treat sick animals and to protect public health by preventing the spread of disease and by keeping pathogens off our plates," Lubroth told delegates at the Prince Mahidol Awards Conference in Bangkok, where the theme of this year's annual conference is AMR and emerging infectious diseases.

"Governments have a responsibility to their country and to the global community to step-up and ensure that adequate regulations for antimicrobial use and distribution are in-place and enforced," said Lubroth, "This responsibility extends to providing incentive programmes and enabling mechanisms to help farmers transition away from an unsustainable dependency on antibiotics."

The FAO is working with Asia-Pacific countries such as Bangladesh, Cambodia, Laos, the Philippines, and Vietnam to develop and implement National Action Plans on AMR to raise awareness, promote good practices and legislation, and boost surveillance. The agency has also developed and piloted the Assessment Tool for Laboratories and Antimicrobial Surveillance Systems (ATLASS) in Cambodia, Indonesia, Laos, Thailand, and Vietnam to help them assess their national AMR surveillance systems and laboratories.
Feb 20 FAO regional office news release

Study finds anti-parasite drug effect against drug-resistant Staph

Investigators looking at the performance of three anti-parasite drugs against Staphylococcus aureus discovered that one of them, ivermectin, demonstrated potent anti-staphylococcal activity against some Staphylococcus isolates, including one that was resistant to methicillin and cefoxitin, according to a study today in Antimicrobial Resistance & Infection Control.

Canadian and Pakistani researchers tested ivermectin, levamisole, and albendazole against 21 S aureus isolates from bovine milk collected in Lahore and Faisalabad, Pakistan.

They found that ivermectin but not the other drugs exhibited a potent anti-staphylococcal activity at the concentrations of 6.25 and 12.5 micrograms per milliliter against two isolates. One of those isolates was sensitive to methicillin and cefoxitin, while the other was resistant to the two drugs.

The authors conclude, "Our novel findings indicate that ivermectin has an anti-bacterial effect against certain S. aureus isolates. However, to comprehend why ivermectin did not inhibit the growth of all Staphylococci needs further investigation."
Feb 20 Antimicrob Resist Infect Control study

News Scan for Feb 20, 2018

News brief

Immune history, not egg-based problems may have affected 2012-13 flu VE

As researchers work on solving the complex puzzle of all the factors that influence flu vaccine effectiveness (VE), researchers today report that low VE of the H3N2 component during the 2012-13 flu season may have been due to poor immune response rather than adaptations in egg-grown vaccine viruses, as previously thought. A team from the University of Chicago, Harvard University, the University of Pennsylvania, Duke University, and the J. Craig Venter Institute reported its findings today in Clinical Infectious Diseases.

That season, the VE for the H3N2 component was estimated at 39%, and during that same season, tests on ferrets immunized with the egg-adapted strain had antibody responses that reacted poorly with circulating H3N2 strains, hinting that egg adaptations were the cause of the drop in vaccine protection.

In the new study, however researchers analyzed blood samples from people who were vaccinated during the 2012-13 season and found no differences in antibody responses to the vaccine and the circulating strains.

Sarah Cobey, PhD, the study's lead author and assistant professor of ecology and evolution at the University of Chicago, said in a press release from the school, "Egg adaptations have variable effects. Sometimes they matter and sometimes they don't, but what seems to make the most difference is immune history."

A 2017 study by some of the same authors found that egg adaptations were linked to mismatches in the most common vaccine formulation for the 2016-17 flu season, and some experts suspect the problem could play a similar role in blunting the vaccine's protection against H3N2 this season.

Cobey said more basic research is needed on how to prompt responses to the right sites on the virus, which will require a better understanding of "original antigenic sin," a hypothesis that the first influenza A virus encountered in childhood strongly influences later responses to similar viruses. "We also need to understand why the vaccine appears to be bad at eliciting responses in some people some of the time. Is there really no response, or are we just not looking in the right places?"
Feb 20 Clin Infect Dis abstract
Feb 20 University of Chicago press release

Multistate Salmonella outbreak linked to kratom supplements

A plant used as a stimulant supplement and herbal alternative to opioids is connected to a multistate outbreak of Salmonella I 4,[5],12:b:- illness, the Centers for Disease Control and Prevention (CDC) announced today.

Kratom, also known as Thang, Kakuam, Thom, Ketom, and Biak, is a plant used as both a stimulant and opioid substitute. So far 28 people in 20 states have fallen ill after consuming kratom in pills, powder, or tea. No specific brand has been identified at this time, the CDC said.

Investigators are using PulseNet, the national subtyping network, to identify other illnesses that may be part of the outbreak, and whole-genome sequencing on samples from sick patients shows that isolates are closely related, suggesting a common infection source. Tests on samples from five people did not identify any antimicrobial resistance patterns.

Eleven out of the 28 patients have been hospitalized, but there have been no deaths. Symptom onset has ranged from Oct 13, 2017 to Jan 30, 2018. More than half of the patients (16) are male, and ill people range in age from 6 to 67 years old. Eight of the 11 people interviewed said they consumed kratom products in the week prior to getting sick.

"At this time, CDC recommends that people not consume kratom in any form," the CDC said. "The investigation indicates that kratom products could be contaminated with Salmonella and could make people sick."
Feb 20 CDC announcement

Nigeria's Lassa fever total grows by 19 new cases

The World Health Organization (WHO) Regional Office for Africa said there were 19 new cases, including 6 deaths, reported last week during Nigeria's ongoing Lassa fever outbreak.

Between Jan 1 and Feb 11 of this year, there have been 615 suspected Lassa fever cases, and 57 deaths, with a case-fatality rate of 9.3%. Of the suspected cases, 193 have been confirmed, of which 47 were fatal. In confirmed cases, the case-fatality rate is 23.9%.

Though Lassa fever is usually transmitted to humans by rats, 14 health care workers have contracted the disease from sick patients during this outbreak. Four of the health care worked have died.

Lassa fever is endemic in Nigeria, but this outbreak is unusually large in size, the WHO said. The virus, which can cause hemorrhagic symptoms that mimic Ebola, is spread through contact with infected rats or via the bodily fluids of an infected person.

"The ongoing Lassa fever outbreak calls for greater attention," the WHO said. "The national authorities and partners need to act quickly to prevent further spread of the disease within the country and to other countries in the region."

As of Feb 12, the WHO had deployed six experts in viral hemorrhagic fevers and 14 support staff to help the Nigerian Centre for Disease Control during this outbreak.
Feb 16 WHO African Regional Office update

H1N1 outpaces H3N2 in latest global flu report

According to a WHO global flu update today, flu is still very active in the Northern Hemisphere, with influenza 2009 H1N1 now outpacing H3N2 alongside rising influenza B activity.

In general, influenza A strains made up 55.2% of lab tested specimens. H1N1 was found in 58% of all influenza A laboratory samples last week, while H3N2 made up 42%. Influenza B, which accounted for 44.8% of specimens, has been rising steadily in the last few weeks, the WHO said, typical at this point in the season. The vast majority of influenza B specimens (92.5%) belonged to the Yamagata lineage, with 7.5% the Victoria lineage.

Flu activity remained high in Canada, Mexico, the United States, and most European countries. Influenza A has dominated North America this season, while Europe is reporting more influenza B. Though hospitalizations still remain high, there are some indicators across the United Kingdom that flu has peaked. Flu activity remains high, however, in northern and eastern European countries.

Influenza also remained high in North Africa, where 2009 H1N1 is the dominant strain. Activity also remained elevated throughout most of East Asia, where influenza B and 2009 H1N1 viruses predominated.

Flu activity was low throughout most of the Southern Hemisphere, including Southeastern Asia and South America. In the Caribbean and Central American countries, influenza activity remained low in general, except for Puerto Rico, which had high activity H3N2 and B viruses co-circulating.
Feb 20 WHO update

H5N6 avian flu detected in Swedish wild bird

Sweden today became the latest country to report highly pathogenic H5N6 avian flu this season, with the agriculture ministry reporting a detection in a white-tailed eagle found sick on Jan 28, according to a notification from the World Organization for Animal Health (OIE).

The bird was found in a nature park in Blekinge County, located in southern Sweden. It died on Feb 1, and samples were sent to the National Veterinary Institute on Feb 13, where the H5N6 finding was confirmed.

Today's report did not say if the virus is the same reassortant that was recently detected in other European countries, mainly in wild birds, and a few Asian countries.
Feb 20 OIE report on H5N6 in Sweden

Study chamber offers snapshot of airborne flu spread in ferrets

A research team based at the University of Hong Kong described a transmission chamber that allowed them to measure and characterize airborne particles involved in flu transmission in ferrets, which they say could help study the transmission of other respiratory pathogens. The group reported their findings today in Proceedings of the National Academy of Sciences (PNAS).

Scientists have been working to clarify the role of contact, droplet, and airborne transmission in the spread of flu and other diseases. The new transmission chamber separates virus-carrying particles by size and helps experts determine the sizes involved in airborne spread among ferrets.

The researchers found that transmission between ferrets occurred by large and fine particles 1.5 micrometers or larger. When they assessed transmissibility of 2009 H1N1 and H3N2 viruses, they found that smaller particles may play a more important role in spread among ferrets than seasonal H3N2, hinting that strains might vary in their transmission modes.

Overall, the findings added more evidence that flu transmission among mammals can occur by droplets as well as fine droplet nuclei. Transmission among ferrets was most efficient before fever onset and continued for 5 days after inoculation.
Feb 20 PNAS study