Stewardship / Resistance Scan for Feb 25, 2020

News brief

CARB-X to fund development of broad-spectrum peptide antibiotics

CARB-X announced today that it will award Peptilogics of Pittsburgh up to $2.56 million in funding to develop a new class of peptide antibiotics with broad activity against drug-resistant bacteria.

The award will support the development of Peptilogics' lead compound, PLG0206, a novel peptide that has demonstrated potent antibacterial activity against multidrug-resistant gram-positive and gram-negative pathogens, with a good safety profile in animals. Because of its ability to disrupt biofilm formation, PLG0206 will be initially aimed at treating serious infections associated with implants such as prosthetic knees and hips.

"Joint replacements are an increasingly common surgical procedure, and infections are the most serious and costly complication of joint replacements," Erin Duffy, PhD, chief of research and development at CARB-X (The Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), said in a press release. "The project is still in the early phases of development, but if successful and approved for use in patients, it could represent tremendous improvement in the treatment of periprosthetic joint infections."

Peptilogics could receive up to $9.61 million in additional funding if the project achieves certain development milestones.

Since launching in 2016, CARB-X has awarded more than $195.6 million to support the development of new antibiotics, diagnostics, vaccines, and other products to combat drug-resistant infections.
Feb 25 CARB-X press release

New drug for complicated urinary tract infections available in US

Drug maker Shionogi & Co. of Osaka, Japan, announced yesterday that cefiderocol, a newly approved antibiotic for treatment of complicated urinary tract infections (cUTIs) caused by gram-negative bacteria is now available for US adults who have limited or no treatment options.

Cefiderocol, sold under the brand name Fetroja, is a cephalosporin antibiotic with a novel mechanism of penetrating the tough outer membrane of gram-negative bacteria and the ability to overcome resistance mechanism used by gram-negative pathogens to evade antibiotics. It was approved by the US Food and Drug Administration on Nov 14, 2019, based on results from a phase 2 clinical trial.

"The infectious disease community faces a serious challenge in combating cUTIs caused by Gram-negative pathogens, leading to high mortality rates," Shionogi president and CEO Akira Kato, PhD, said in a company news release. "This illustrates a dire need for a treatment option able to overcome many mechanisms of resistance in Gram-negative bacteria."

The labeling for cefiderocol comes with a warning about higher all-cause mortality found in patients with highly drug-resistant infections who were treated with the drug in another clinical trial, compared with patients treated with the best available therapy. The cause of the increase in mortality has not been established.
Feb 24 Shionogi press release

OIE: 77% of nations don't use antibiotics to promote animal growth

The World Organization for Animal Health (OIE) yesterday said more than three fourths of countries do not use any antibiotics for animal growth promotion, according to findings in its fourth annual report on global use of antibiotics in food-producing animals.

The report includes information on veterinary antibiotic use submitted by 153 OIE members in 2018, an increase of 18% since data collections began in 2015. Of these 153 countries, 118 (77%) provided data on quantities of antimicrobial agents sold for use in food-producing animals, an increase of 33% since 2015. Most countries (111 of 118, 94%) submitted data for only 1 year from 2016 to 2018. Progress was observed from 31 countries that had reported barriers in reporting quantitative antibiotic data during previous rounds of data collection.

A total of 118 countries (77%) reported that they did not use any antibiotics for growth promotion in animals as of 2018, either with or without legislation or regulations.

The report also includes an estimate of antibiotic use adjusted by animal biomass in 92 countries, which helps provide context for antibiotic sales data and can help explain trends and fluctuations in antibiotic use over time and between regions. The global estimate of antibiotics used in animals in 2016 adjusted by animal biomass was 144.39 milligrams per kilogram (mg/kg).

Regional comparison showed that Asia, the Far East, and Oceania reported the most antibiotics intended for use in animals (273.72 mg/kg) among the four global regions. Comparisons of the 2016 data with data from 2014 and 2015 showed that Europe's reported antibiotic use adjusted by animal biomass fell from 2014 to 2016, while Africa's remained at a similar level despite the contributions from more countries, and animal antibiotic use rose in the Americas. But the OIE cautions that changes in reporting countries and in regional biomass coverage across years of analysis, as well as differences in species composition, leave room for uncertainty.

The OIE says that, as more data on animal populations become globally available, the methodology for calculation of animal biomass will be refined.
Feb 24 OIE report

News Scan for Feb 25, 2020

News brief

One new MERS case reported in Saudi Arabia; WHO details recent cases

Saudi Arabia's Ministry of Health (MOH) reported a new MERS-CoV case today. This raises the number of MERS cases recorded this month to 11.

The case involves a 74-year-old man from Hafar Al Batin whose exposure to MERS-CoV (Middle East respiratory syndrome coronavirus) is listed as primary, meaning it is unlikely he contracted the virus from another person. The MOH said the man had camel contact, a known risk factor for MERS.

Yesterday the World Health Organization (WHO) published a report on MERS cases recorded in December and January in Saudi Arabia. In total there were 19 cases and 8 deaths. Of note was a six-person hospital cluster in Aseer that included 3 healthcare workers, 2 patients, and 1 visitor. One infected person in this cluster died on Feb 4.

The WHO said that, since 2012, it has received reports of 2,519 laboratory-confirmed MERS-CoV infection cases, with 866 associated deaths. The vast majority of these cases have been in Saudi Arabia.
Feb 25 Saudi MOH report
Feb 24 WHO report

FDA approves first adjuvanted 4-strain seasonal flu vaccine for seniors

The US Food and Drug Administration (FDA) has approved the first adjuvanted quadrivalent (four-strain) seasonal influenza vaccine for people 65 years and older, Fluad Quadrivalent, according to manufacturer Seqirus, Inc.

The vaccine includes Seqirus's MF59 adjuvant, which is an immune-boosting additive, according to a news release yesterday from Seqirus, based in Summit, New Jersey. "Adults 65 years and older are at high risk for influenza-related complications each season and it is important to have influenza vaccines to help protect this vulnerable population," said Anjana Narain, Seqirus executive vice president and general manager.

Unpublished data presented by Seqirus in December showed that Fluad Quadrivalent is more effective in reducing flu-related hospitalizations than a trivalent (three-strain) influenza vaccine (TIV) in adults 65 and older living in nursing facilities in 2016-17. In the study, 823 nursing facilities were randomly assigned to offer Fluad (21,278 residents) or a TIV (21,269 residents), and Fluad was 20% more effective than TIV in reducing influenza- and pneumonia-related hospitalizations.

Older adults are at elevated risk for complications from influenza. During the 2017-18 influenza season, 70% of influenza-related hospitalizations and 90% of related deaths occurred in this age range, Seqirus said. The vaccine also tends to be less effective in seniors because of their reduced immune response.
Feb 24 Seqirus news release
Dec 10, 2019, CIDRAP Flu Scan on earlier data

Study: No need for adult tetanus, diphtheria booster if vaccinated as kids

Adults fully vaccinated as children can safely forego tetanus and diphtheria booster shots, according to a study published February 25 in Clinical Infectious Diseases.

After comparing data from millions of people in 31 North American and European countries from 2001 and 2016, researchers at the Oregon Health & Science University (OHSU) identified no statistically significant difference in disease rates in countries that require boosters for adults and those that don't. The investigators compared adults in countries that vaccinate adults against the two diseases every 5 to 20 years with those that don't.

The Advisory Committee on Immunization Practices at the Centers for Disease Control and Prevention calls for boosters every 10 years, but the World Health Organization recently recommended boosters only for adults who didn't receive a full series as children.

"To be clear, this study is pro-vaccine," says the study's lead author, Mark Slifka, PhD, a professor of microbiology and immunology at OHSU, in a school news relese. "Everyone should get their series of tetanus and diphtheria shots when they're children. But once they have done that, our data indicates they should be protected for life."

The study follows one that Slifka and colleagues published in 2016 involving 546 adults, which demonstrated that the vaccine produces at least 30 years of protective immunity.

The United States could save roughly $1 billion each year in medical costs if it required fewer vaccinations in adults, the researchers said in the news release. It could also allow improved allocation of healthcare resources in countries with low vaccination rates.

Tetanus affects about 30 people in the United States each year, with 1 or 2 out of 10 cases leading to death. Diphtheria has been reported in only five people in the United States over the past decade, and about 1 in 10 cases is fatal.
Feb 25 Clin Infect Dis abstract
Feb 25 OHSU news release
Mar 21, 2016, previous study

High-path avian flu kills poultry in Vietnam, Poland, and Bulgaria

Vietnam, Poland, and Bulgaria all reported multiple outbreaks of highly pathogenic avian flu, according to the latest reports from the World Organization for Animal Health (OIE).

Animal health officials in Vietnam confirmed 13 H5N6 outbreaks in village flocks ranging from 37 to 4,075 poultry, all in the north. Six outbreaks are in Thanh Hoa province, 2 in Ha Noi, and 1 each in Bac Ninh, Ninh Binh, Thai Binh, Nghe An, and Hai Pong provinces. The outbreaks began Feb 15 to Feb 21. All told, the virus sickened 6,680 birds and killed 4,274 among 25,375 susceptible poultry.

Poland, meanwhile, confirmed seven H5N8 outbreaks in the country's midsection affecting more than 170,000 birds. The seven affected farms are in five provinces (voivodeships), with the outbreaks beginning on Feb 7 through Feb 22. The virus struck 47,254 poultry and killed 35,286 across all the farms, out of a total of 170,389 birds. The surviving birds were culled to prevent further disease spread.

The same virus struck two farms in Bulgaria yesterday, both in Plovdiv province in south central Bulgaria. One housed more than 11,000 birds and the second almost five times that number. The high-path H5N8 virus killed 54 poultry on both farms combined, out of 67,037 birds. This is the first report of this avian flu strain in the country.
Feb 25 OIE report on H5N6 in Vietnam
Feb 25 OIE report on H5N8 in Poland
Feb 24 OIE report on H5N8 in Bulgaria