Stewardship / Resistance Scan for Sep 06, 2017

News brief

Precision antimicrobial drug candidate has added benefits, study finds

A team of scientists in the United States and the United Kingdom have identified additional benefits in a new class of antibacterial compounds that specifically kill Clostridium difficile strains without disrupting beneficial bacteria in the gut, according to a study today in Science Translational Medicine.

The compounds, called Avidocin-CDs, have previously been shown to kill specific C difficile strains, including the hypervirulent ribotype 027, and prevent them from colonizing mice. Avidocin-CDs work by attaching to the outer membrane of C difficile bacteria and poking holes in it. Their ability to kill C difficile while sparing beneficial gut bacteria has made them a potential candidate for further development as a human therapeutic. Broad-spectrum antibiotics currently used to treat C difficile are problematic because they wipe out good gut bacteria, which can leave patients at risk for recurrent infections.

In this study, further exploration of Avidocin-CDs showed that the compounds specifically bind to a crucial component of a protective protein shell called the S-layer. With that information in hand, the scientists were able to develop a panel of Avidocin-CDs with killing activity in vitro against 60 different C difficile clinical isolates encompassing all 12 known S-layer types. But the scientists found that the compounds have an additional advantage. While mutations caused some of the C difficile bacteria to lose their S-layers and become resistant to the Avidocin-CDs, there was a trade-off: In hamster models, Avidocin-CD-resistant bacteria produced less toxin, fewer spores, and were less virulent.

"The precise killing activity of Avidocin-CDs makes them attractive agents for both treatment and prevention because they can be administered to patients without altering the diversity of the complex gut microbiota," the authors write. "In addition, when resistance does emerge, Avidocin-CDs force the pathogen to sacrifice virulence for viability, making the potential clinical impact of resistance inconsequential."
Sep 6 Sci Transl Med study

Nations pledge millions for new antibiotic development

Led by Germany, a handful of nations and foundations have pledged 56.5 million euros ($65.7 million US) to the Global Antibiotic Research & Development Partnership (GARDP) to develop new treatments for antibiotic resistant infections.

The money, pledged during a GARDP fundraising event in Berlin, will support drug development in GARDP's four program areas: New treatments for sexually transmitted infections, with a focus on drug-resistant gonorrhea; Antimicrobial memory recovery, which aims to use knowledge from abandoned antibiotic development projects to help identify new drug opportunities; New treatment regimens for neonatal sepsis; and new antibiotics specifically adapted for children.

The bulk of the money was pledged by Germany (51.35 million euros), with smaller contributions from the Netherlands, Switzerland, South Africa, Luxembourg, the United Kingdom, and the UK-based Wellcome Trust.

"With this support we can take concrete strides in making our vision a reality, reaching our goal of delivering up to four new treatments by 2023, and striving to improve the lives of all patients who need affordable and effective new antibiotics," GARDP president Manica Balasegaram, MRCP, MSc, said in a press release.

GARDP was established in 2016 by the World Health Organization and the Drugs for Neglected Diseases initiative.
Sep 4 GARDP press release

Canada releases antimicrobial resistance framework

Canada yesterday released a nationwide framework to spearhead a coordinated effort from all levels of government and across all sectors—including public health, healthcare, animal health, agriculture, industry, and academia—to address antimicrobial resistance (AMR), according to a Health Canada press release.

"Antimicrobial resistance is a serious global health threat that cannot be overlooked," said Minister of Health Ginette Petitpas. "Our government is committed to taking action to mitigate the impact of antimicrobial resistance on Canadians. We are enhancing surveillance, promoting good infection prevention and control practices, promoting the responsible use of antimicrobials, and supporting research and innovation for new prevention and treatment products."

Minister of Agriculture and Agri-Food Lawrence MacAulay added, "The prudent use of antimicrobials is an important issue involving not only human health, but the health of animals, food safety, environment and the economy. Agriculture must play an important role in containing the development and spread of antimicrobial resistance."

The Pan-Canadian Framework, as it is called, builds on the AMR work that is already under way in human and animal health sectors and strives to connect various efforts across the country, Health Canada said in the report. "The Framework provides the foundation to spur further action and collaboration among partners in human and animal sectors to minimize the impact of AMR, and to ensure that antimicrobials will continue to be an effective tool in protecting the health of Canadians."
Sep 5 Health Canada news release
Sep 5 Health Canada report

UK pharmacy group details steps to better antimicrobial stewardship

Declaring, "Pharmacist expertise and clinical knowledge must be fully utilised to ensure appropriate use of antibiotics and improve stewardship" to reduce AMR, the UK Royal Pharmaceutical Society (RPS) this week published a policy report and related antimicrobial stewardship quick reference guide geared toward pharmacists.

The policy document focuses on pharmacists' role as part of a multidisciplinary approach in tackling the challenges of inappropriate use of antibiotics. The recommendations in the policy are geared toward helping the country reach its goal of reducing inappropriate antibiotic prescribing by 50% by 2020.

The policy report and quick reference guide, aim to complement recommendations made by the Pharmaceutical Group of the European Union and the International Pharmaceutical Federation in the global fight against AMR, according to the RPS.

The six policy recommendations focus on (1) pharmacist leadership, (2) multidisciplinary teams, (3) pharmacist access to the patient health record, (4) public awareness, (5) further research, and (6) education and training for pharmacists.
Sep 3 RPS policy report
Sep 3 RPS quick reference guide

News Scan for Sep 06, 2017

News brief

Two new Saudi MERS cases announced as WHO details household cluster

The Saudi Arabian Ministry of Health (MOH) reported two new cases of MERS-CoV yesterday and today.

Yesterday, a 37-year-old Saudi man from Al Hofuf was diagnosed as having MERS-CoV (Middle East respiratory syndrome coronavirus). He is in critical condition. The MOH said the source of his infection was primary, meaning he likely did not contract the disease from another person.

Today a 78-year-old Saudi man in Riyadh is in stable condition after being diagnosed as having MERS. He had direct contact with camels, a known risk factor for the virus.

The new cases raise Saudi Arabia's MERS-CoV case count since 2012 to 1,719, including 693 deaths. Eight patients are still being treated, according to the MOH.
Sep 5 MOH report
Sep 6 MOH report

Also today, the World Health Organization (WHO) described 12 MERS cases reported by the MOH between Aug 13 and 30. Included in these cases are 6 patients from Dumah Al Jandal, who were household contacts of previous cases in that city. They did not contract MERS during an early-August healthcare outbreak in that city, the WHO said.

According to the WHO, officials have reported 2,079 laboratory-confirmed cases of MERS-CoV worldwide, including at least 722 related deaths, since 2012.
Sep 6 WHO report

Meta-analysis shows better performance for newer rapid flu tests

Newer commercially available rapid tests for diagnosing influenza A and B are much more sensitive than traditional rapid tests and are just as specific, a Canadian-led research team reported yesterday in Annals of Internal Medicine.

The group's meta-analysis of 162 studies provides an update of a similar study in 2012 that found traditional rapid influenza diagnostic tests (RIDTs) were highly specific but poorly sensitive when compared to reverse-transcriptase polymerase chain reaction as the reference test. Since then, two other novel rapid tests have come on the market, digital immunoassays (DIAs) and rapid nucleic amplification tests (NAATs).

The scientists noted that rapid and accurate flu diagnosis paves the way for promptly starting antiviral treatment, leads to fewer other tests and hospitalizations, supports hospital infection control measures, and results in less unnecessary antibiotic use.

Based on their analysis, pooled sensitivities for DIAs and NAATs were markedly higher than RIDTs, and the use of DIAs and NAATs improved the detection of true cases of flu by 25 and 40 percentage points, respectively, compared with RIDTs.

Similar to the group's earlier findings, the researchers found that traditional RIDTs have sensitivities (54.4% for influenza A and 53.2% for influenza B) well below new US Food and Drug Administration (FDA) performance requirements that were released in February 2017. The authors added that regulatory agencies will likely phase out traditional RIDTs because of their poor sensitivity, especially in adults.

In a related editorial in the same issue, Michael Ison, MD, MS, an infectious disease specialist at the Northwestern University Feinberg School of Medicine in Chicago, wrote that the next-generations tests are simple, fast, and approved for point-of-case use by nonlaboratory staff, adding that their sensitivity approaches that of reverse transcriptase polymerase chain reaction testing. He added that the newer tests could improve care. "Increased availability and use of such assays likely will drive more appropriate early use of antivirals, may decrease unnecessary antibacterial therapy, and may improve patient outcomes."
Sep 5 Ann Intern Med study
Sep 5 Ann Intern Med editorial

Colombian case-control study builds support for Zika-GBS link

On the heels of similar findings from Brazil last week, a case-control study from Colombia found more evidence of a link between Zika illness and Guillain-Barre syndrome (GBS) and a much higher incidence of the condition in older people.

Researchers from Colombia and their collaborators at the US Centers for Disease Control and Prevention (CDC) reported their findings Sep 4 in the Journal of the Neurological Sciences.

They interviewed and tested 47 patients with GBS who were reported to health officials in Barranquilla, Colombia, from Oct 1, 2015, to Apr 2, 2016. The team compared the findings and incidence with two age-range matched controls from the same neighborhood as each GBS patient.

Incidence of GBS was 10 times higher in people age 60 and older compared with those younger than 20. Last week's Brazilian study also found that the incidence was 10 times higher in the oldest group than in the youngest group.

The Colombian study also found that those with suspected or probable Zika disease also had higher odds of developing GBS. In addition, the researchers found that, similar to reports from other regions, peaks in Zika disease and GBS coincided.
Sep 4 J Neurol Sci abstract
Aug 31 CIDRAP News story "Case-control study finds more evidence of Zika-GBS link"

CDC reports more Cyclospora cases in multistate outbreak

In its latest update, the CDC late last week reported 48 more cases of Cyclospora since its previous weekly report. Alongside a normal summer rise in travel-related Cyclospora cases, the CDC on Aug 7 notified health providers that it was investigating several locally acquired cases in several states, but so far a food source for the illnesses hasn't been found.

As of Aug 30, the CDC has received reports of 930 lab-confirmed cyclosporiasis cases this year, and at least 514 (55%) of the patients didn't report international travel and were sick on or before May 1, when health officials normally see a rise in illnesses. Of the 48 new cases, 36 involved no history of international travel. The latest illness onset is Aug 15.

Two more states reported locally acquired cases, raising the total to 36, the CDC said. Texas, the hardest-hit state by far, has been investigating a rise in cases that began in the middle of June. As of Aug 22, the Texas Department of State Health Services (TDSHS) reported 259 infections.
Sep 1 CDC update
Aug 22 TDSHS update