ASP Scan (Weekly) for Sep 08, 2017

ESBL-E in pregnant women
Antimicrobial resistance in Southeast Asia
Precision antimicrobials
Money for antibiotic development
Canada AMR framework
Pharmacist stewardship
CRE treatment

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Study: ESBL-E present in 17% of pregnant, postpartum women in Africa

A systematic review by South African experts yesterday of 10 studies estimates the prevalence of colonization with extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL-E) at 17% in pregnant or postpartum African women, higher than women in middle- to high-income settings.

The results represent a risk for colonization of neonates with ESBL-E.

ESBL-E, an enzyme produced by bacteria, confers resistance to several antibiotics, including penicillins, cephalosporins and monobactams. Among pregnant and postpartum women, ESBL-E is commonly associated with resistant urinary tract and bloodstream infections.

The study, published in the International Journal of Infectious Diseases, included seven studies on pregnant women and three on postpartum women conducted throughout Africa. The researchers found ESBL-E isolates were more prevalent in community settings than in hospitals (22% vs 14%). The most frequently reported ESBL-encoding gene was CTX-M, which has cefotaxime hydrolyzing capabilities.

The authors explained the difference between community and hospital prevalence by suggesting wider misuse of antibiotics in community settings and poor water sanitation conditions.

"More robust studies are needed to understand how frequently pregnant and/or post-partum women get colonized or infected with ESBL-E in Africa, the related risk factors in both community and hospital settings to inform future interventions to reduce their rates," they concluded.
Sep 7 Int J Infect Dis study


Articles examine AMR in Southeast Asia

The British Medical Journal (BMJ) has published a collection of articles on antimicrobial resistance (AMR) in Southeast Asia.

The collection is a series of 15 articles that highlight how AMR has become not just a medical issue but also a political, social, and economic problem in the World Health Organization's South East Asia region, which includes Bangladesh, Bhutan, India, Indonesia, Maldives, Myanmar, Nepal, North Korea, Sri Lanka, Thailand, and Timor-Leste. The region, home to approximately 1.8 billion people, is considered to have a high risk for the emergence and spread of AMR, due to inadequate housing and sanitation, poor infection prevention and control in healthcare settings, and widespread and unregulated antibiotic use.

Among the papers included in the collection are a risk assessment for AMR in the region, a review of situational analyses of antimicrobial use and stewardship conducted in all 11 countries, and an in-depth look at AMR initiatives in India, Indonesia, and Thailand. The collection also includes articles on antimicrobial use and interventions in food animal production, antibiotic residues found in the environment, and the impact of drug resistance on treatment for malaria, tuberculosis (TB), and HIV. The region has half the global incident cases of TB and one-tenth of the estimated burden of malaria and HIV.

The region's member states have pledged to develop national action plans to combat AMR, using a One Health approach aimed at antibiotic use in agriculture, livestock, and human health.
Sep 5 BMJ special collection


Precision antimicrobial drug candidate has added benefits, study finds

Originally published by CIDRAP News Sep 6

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

Originally published by CIDRAP News Sep 6

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

Originally published by CIDRAP News Sep 6

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

Originally published by CIDRAP News Sep 6

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


Study: Combination treatment may be better than colistin for CRE infections

Originally published by CIDRAP News Sep 5

A study of US patients with carbapenem-resistant Enterobacteriaceae (CRE) infections has found that ceftazidime-avibactam may be a reasonable treatment alternative to colistin, researchers reported yesterday in Clinical Infectious Diseases.

The results come from CRACKLE (Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae), a prospective, observational study of patients at 18 US hospitals who have had a culture from which CRE is isolated. In this arm of the study, investigators evaluated 137 patients initially treated with either ceftazidime-avibactam, a combination therapy recently approved by the Food and Drug Administration for treatment of complicated urinary tract and intra-abdominal infections, or colistin, a standard yet toxic treatment for multidrug-resistant CRE infections.

The patients were chronically and acutely ill, with almost half (46%) presenting with bloodstream infections. Other common infections included respiratory tract infection (22%) and urinary tract infections (19%). Almost all patients (97%) were infected with Klebsiella pneumoniae. Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat analyses with partial credit and desirability of outcome ranking (DOOR) approaches, and analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW).

Of the 137 patients, 38 initially received ceftazidime-avibactam and 99 were treated with colistin. IPTW-adjusted all-cause hospital mortality at 30 days was 9% in the ceftazidime-avibactam group compared with 32% for the colistin patients, representing a 23% difference in mortality. When analyzing patient disposition at 30 days, patients treated with ceftazidime-avibactam were found to have an IPTW-adjusted 64% probability of a better outcome compared with patients treated with colistin.

"The use of ceftazidime-avibactam was associated with improved clinical outcomes, especially decreased all-cause hospital mortality, and improved benefit-risk outcome," the authors write. They say the findings will need to be confirmed in a randomized controlled trial.
Sep 4 Clin Infect Dis abstract

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