Call for action on AMR by the Wellcome Trust, Berlin
The Call to Action event in Berlin on October 12 and 13 was organized by the Wellcome Trust, in partnership with the UK, Thai, and Ghanaian Governments, and the United Nations Foundation aiming to address “fragile” progress on tackling Superbugs, to use the terms of the UN Foundation news report. AcdeBMR/WAAAR President Dr Jean Carlet participated in the event.
The call’s key word was ‘fragile’.
“Analysis by Wellcome and the UN Foundation shows that while 151 of 195 countries are developing an action plan to tackle drug-resistant infections, only half address the threat across human and animal health and the environment. Just 1 in 5 commit to reducing antibiotic use, improving hygiene, and preserving antibiotics of last resort, and only 5 percent are adequately funded and monitored.”
The United Nations declaration had called for the establishment of an ad hoc Inter-Agency Coordination Group (IACG), with three co-convenors:
England’s Chief Medical Officer, Professor Dame Sally Davies
Professor Junshi Chen, Senior Research Professor of Institute of Nutrition and Food Safety - Chinese Center for Disease Control and Prevention Beijing, China
Ms Martha Gyansa-Lutterodt, Director of Pharmaceutical Services and Chief Pharmacist of Ghana
The IACG will produce a report to present to the UN Secretary-General during the 73rd session of the UNGA in 2018 and 2019.
Dame Sally Davies, in reports of the event and in interviews with the press stressed that if many countries in the world have their own national AMR plans by now, the key word now is “implementation”.
The main outcome of the meeting was the launch of the Global antibiotic resistant tracking project to help governmental leaders addressing AMR
WAAAR’s president Dr Jean Carlet, who attended the Berlin meeting, noted that the effort was basically lead by the US-UK, with weak representation from France, and more surprisingly limited presence from Germany, considering that the meeting was held in Berlin, and followed Germany’s lead on AMR for the G20 meeting in 2007.
From not-for-profit civil society, Jayasree K. Iyer, Executive Director of the Access to Medicine Foundation talked about Antimicrobial Resistance Benchmark, (which AMR Times reported on in previous edition).
From industry: the International Federation of Pharmaceutical Manufacturers & Associations released a statement on global call for action on AMR.
The JPIAMR also issued a press release on the Call, where the JPIAMR Initiative announced 3 calls to fund research projects with a preliminary budget of 15 million euros, targeting pathogens along the list established by the WHO. JPIAMR also reminds readers of the Virtual Research Hub, the scientific collaboration platform recently created and, last, proposes to do a mapping of all the efforts in terms of R&D on this issue.
UN Foundation: http://www.unfoundation.org/news-and-media/press-releases/2017/global-leaders-urged-to-address-fragile-progress-on-tackling-superbugs.html?referrer=https://t.co/sLFW0unr9A
Progress report by the Wellcome Trust: https://wellcome.ac.uk/sites/default/files/sustaining-global-action-on-antimicrobial-resistance.pdf
Meeting Summary: https://www.linkedin.com/pulse/one-persons-take-call-action-antimicrobial-resistance-michael-levy/?trackingId=8nFzEr1gbtPzxw9cuerolA%3D%3D
The Global antibiotic resistant tracking project: http://www.bmj.com/content/359/bmj.j4769
CDC awards $9 million to investigators to combat AMR
CDC: excerpts of press release:
The Centers for Disease Control and Prevention (CDC) is awarding more than $9 million to 25 investigators to pilot innovative solutions and explore knowledge gaps about antibiotic resistance related to the human microbiome, healthcare settings, and surface water and soil.
To protect people, CDC and investigators will:
- Discover and evaluate new strategies that protect patients from resistance threats in healthcare settings and improve healthcare quality.
- Investigate the human microbiome and pinpoint effective prevention strategies that protect people, their microbiomes, and the effectiveness of antibiotics.
- Examine the impact of antibiotic resistance elements in environmental settings, like surface water and soil, to determine potential downstream impacts on human health. Resistance elements are genetic material that can move between, combine with bacteria, and contribute to antibiotic resistance. Examine the impact of antibiotic resistance elements in environmental settings, like surface water and soil, to determine potential downstream impacts on human health. Resistance elements are genetic material that can move between, combine with bacteria, and contribute to antibiotic resistance.
Germs continue to find new ways to resist drugs. Data from this work will help CDC protect people (e.g., detecting reservoirs of resistant germs, informing outbreak response, and preventing future infections).
These awards are part of the Antibiotic Resistance Solutions Initiative... In fiscal years 2016 and 2017, CDC’s Antibiotic Resistance Solutions Initiative awarded more than $24 million to investigators through a broad agency announcement to fight antibiotic resistance.
For descriptions of the new projects: www.cdc.gov/drugresistance/solutions-initiative/innovations-to-slow-AR.
Press release: CARB-X awards Amicrobe $2.48M to accelerate the development of Amicidin-β topical antimicrobial
Scientific diversity of CARB-X portfolio boosted with Amicrobe’s ground-breaking research on topically applied antimicrobials for use on infected tissue in surgical, emergency and post-disaster settings
BOSTON, MA – October 24, 2017 – CARB-X announced today an award of up to $2.48 million to Amicrobe Inc. to accelerate the development of a new bioengineered antimicrobial designed for direct application to contaminated and infected tissues, including those of surgery and trauma. The award commits funding of up to $2.48 million in an initial period, with the possibility of up to $3.76 million more based on the achievement of milestones to the satisfaction of CARB-X.
"The addition of the Amicidin-β program, which represents the first topically applied antimicrobial in the CARB-X portfolio, expands the diversity of our pipeline and reflects a novel approach against drug-resistant infections," said Kevin Outterson, Executive Director of CARB-X.
(...) "The era of antimicrobial resistance challenges all of us to bring forward new technologies and products to prevent and treat life-threatening infections" said Michael P. Bevilacqua, M.D., Ph.D., CEO and CSO at Amicrobe, a Carlsbad, CA-based firm. "At Amicrobe, we are very pleased to receive the recognition and support of CARB-X to accelerate our Amicidin-β program."
Diagnostics initiatives and announcements : The value of diagnostics to combat antimicrobial resistance by optimising antibiotic use
A New initiative to promote diagnostic tools development and use is in the works bringing together the Innovative Medicines Initiatives and the Wellcome Trust.
The call is available on the IMI website:
The value of diagnostics to combat antimicrobial resistance by optimising antibiotic use
The call says: Diagnostics play a critical role in guiding treatment in infectious diseases. However, the value of diagnostics as a critical component of antimicrobial stewardship programmes is not fully established throughout Europe, with guidelines, funding and policy varying in each country. This hinders the adoption and use of currently available diagnostic tests by health professionals, as well as the development of advanced or innovative diagnostic tools. Therefore, a pan-European approach is required, to demonstrate the medical, economical and public health value of diagnostics for combating AMR: rapid and reliable characterisation of pathogens and their antibiotic resistance characteristics along with host susceptibility biomarkers. One way to determine the full value of diagnostics, and the optimal means of addressing the multitude of obstacles for their creation, valuation and deployment, is to analyse all these aspects in a standardised clinical trial network.
The overuse of antibiotics and the underuse of diagnostics occur within the entire breadth of healthcare: primary care, as well as hospitals with acute care, rehabilitation facilities and long-term care facilities, where most of the emerging antibiotic-resistant pathogens can be found. In Europe, 30-50% of antibiotics are prescribed unnecessarily, according to estimates from the European Centre for Disease Prevention and Control (ECDC)
Need and opportunity for public-private collaborative research
The urgent action to address the escalating problem of antibiotic resistance requires cooperation amongst industry, academia, patients and patient groups, policy makers, public health experts and healthcare decisionmakers in order to implement critical solutions, including impactful diagnostics, which will allow preserving the efficacy of the antibiotics currently available or in development.
Multiple diagnostics already exist which can be used to accurately and efficiently guide and improve antibiotic prescribing, but they are under-utilised across Europe.
The main objective of this action is to understand, demonstrate, and quantify the value of diagnostics and the obstacles to their adoption and use in the framework of a Standardised Care Network in order to combat antimicrobial resistance (AMR) by optimising antibiotic use in Europe.
Health economic models for the use of diagnostics must be developed to:
§ address the costs and benefits of the use of diagnostics and their impact on antibiotic prescribing;
§ propose funding models (e.g. research incentives, reimbursement framework, adoption motivation) which would facilitate the development, introduction, deployment and use of diagnostics into routine medical care.
Read all on the IMI website:
The ImmunoXpert is a pioneering in-vitro diagnostic test that accurately distinguishes between bacterial and viral infections based on the patient’s immune response.
“A novel assay that integrates measurements of blood-borne host-proteins including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interferon γ-induced protein-10 (IP-10), and C-reactive protein (CRP) has been developed to assist in differentiation between bacterial and viral disease.”, they report, “A large team of scientists led by those at the Faculty of Medicine at the Technion-Israel Institute of Technology (Haifa, Israel) performed double-blind, multicenter assay evaluation using serum remnants collected at five pediatric emergency departments and two wards from children older than three months to less than 18 years, including 68 without and 529 with suspicion of acute infection. Infectious cohort inclusion criteria were fever equal to or greater than 38 °C and symptom duration equal to or less than seven days.
The novel blood test, ImmunoXpert accurately distinguishes between bacterial and viral infections in children.
Kfir Oved, MD, PhD, co-founder and chief technology officer at MeMed, and a co-author of the study, said, “Our solution was to try to bring a very simple solution that, within a few minutes, a few drops of blood, and with a relatively high level of accuracy we would provide this exact information to physicians.”
The scientific article, Validation of a Novel Assay to Distinguish Bacterial and Viral Infections is published in Pediatrics Sept 2017, main corresponding author : Isaac Srugo, MD, Department of Pediatrics, Bnai-Zion Medical Center, Israel. ”http://pediatrics.aappublications.org/content/early/2017/09/11/peds.2016-3453
GenePOC launches its Group B Streptococcus Direct Swab (DS) molecular test in Europe
Québec, Canada–October 12, 2017 – GenePOC, Inc., a member of the Debiopharm Group, announced the launch of its 2nd assay this year, GenePOC™ GBS DS, for use on the revogene™ instrument. GenePOC GBS DS at intrapartum will aid to minimize the risk of GBS transmission from the mother to their newborn and will help to optimize antibiotic stewardship.
About GBS screening in Europe : Still today, GBS is the leading cause of infection in infants worldwide with a fatality rate between 4-6%. There is an unmet clinical need as many countries have introduced guidelines to prevent early onset disease in newborns while other countries do not follow any guidelines yet.
In the current clinical strategy, the detection of Group B Streptococcus colonization in pregnant women is performed between 35 and 37 weeks of gestation and, if a positive result is obtained, an intrapartum antibiotic prophylaxis (IAP) is administrated to the mother. However, studies have shown that up to 61, 4% of term infants with GBS disease are born to women who have been falsely diagnosed negative or whose colonization status has changed from the time of antenatal testing to the time of delivery.
"Intrapartum GBS testing is superior to antenatal testing at week 35-37. However, this requires very fast and easy methods. The GBS DS assay from GenePOC allows sensitive diagnosis of GBS just prior to delivery, making intrapartum GBS screening possible and resulting in optimized detection of patients at risk" said Prof. Dr. med. Lutz von Müller from Christophorus-Kliniken, Coesfeld, Germany. Dr Von Müller studied the detection of Group B Streptococcus (GBS) colonization before delivery and compared the new GenePOC molecular system to culture.
"What we are passionate about at GenePOC is to eliminating the highly debilitating effects of early onset diseases which include meningitis, pneumonia and in some cases death. In launching our new GenePOC GBS DS assay, we will be directly addressing that unmet clinical need..." said Patrice Allibert, PhD, CEO of GenePOC. "The GenePOC offer is a breakthrough solution for testing GBS carriage while the mother is in labor.
Web=links: GenePOC www.genepoc-diagnostics.com
Roche, Warp Drive Launch Up-to-$387M Natural Antibiotics Collaboration
Roche will partner with Warp Drive Bio to develop new classes of antibiotics against multidrug-resistant bacterial infections, through a collaboration that will generate up-to-$387 million-plus for Warp Drive, the Cambridge, MA-based biotech reported this week.
The partnership is designed to advance “multiple” novel classes of natural antibiotics that show activity against clinically important, drug-resistant, Gram-negative pathogens by applying Warp Drive’s Genome Mining™ platform, the company said.
Genome Mining is a "genomes to molecules" synthetic biology platform designed to search the genomes of microbes in order to uncover genes that encode hidden natural products, then engineer them to produce novel drugs. Warp Drive says it has assembled a genomic database of over 135,000 strains with the potential to encode more than four million biosynthetic gene clusters.
Using Genome Mining, Warp Drive plans to identify and evaluate over 100 novel classes of potential antibiotics previously undiscovered, thus never analyzed for their impact on human health. Microbial genome sequencing has revealed the enormous biosynthetic capacity of Actinomycetes, with about 90% to 95% of all biosynthetic pathways being "silent" or "cryptic" under standard laboratory fermentation conditions, according to the company.
“Our ultimate vision for this program is that we will identify the complete natural product armamentarium of the Actinomycete family, thus creating a unique new set of pharmaceutical chemical diversity with broad application in the discovery of new human therapeutics,” Warp Drive states on its website.
According to Warp Drive, 10 classes of natural antibiotics have been approved for patient use, compared with five classes of synthetic antibiotics.
The last antibiotic from a novel natural class approved by the FDA was Cubicin® (daptomycin), discovered more than 30 years ago but for which authorization was granted in 2003 to Cubist Pharmaceuticals, acquired by Merck & Co. in 2014 for $9.5 billion.
Warp Drive Bio was launched in 2012 with $125 million in initial funding, through a strategic partnership with Sanofi and with capital from Third Rock Ventures and Greylock Partners. Last year, Sanofi and Warp Drive overhauled their partnership, launching a five-year, up-to-$750 million collaboration designed to discover novel oncology therapeutics and antibiotics by using Genome Mining and Warp Drive’s Small Molecule Assisted Receptor Targeting (SMART™) platform.
New Zealand AMR action plan
The New Zealand ministry of health and ministry of primary industry along with other 11 organizations and professional bodies representing human health, animal health and agriculture sector forming "the antimicrobial action planning group" have issued the New Zealand Antimicrobial resistance action plan that was announced at the 70th World Health Assembly of 2017.
The report stressed the importance of implementation of one health approach in order to achieve the goals of the action plan for the next five years; ensuring the effectiveness and availability of antimicrobials to manage diseases when needed in the future, and improving the knowledge needed to combat the development and spread of AMR.
According to the report, the five key objectives that will be targeted are; Improving awareness and understanding, surveillance and research, stewardship, governance, collaboration and investment as well as prevention and control measures.
The report goes through every objective and discusses in details the ongoing activities and the prioritized ones in every upcoming year for each area of action.
New chapter in tackling AMR in Thailand
In this article, the author Nithima Sumpradit and her colleagues describe the experience of Thailand in developing its national strategic plan on AMR and highlight the need for sustainable political commitment and multi-sectoral collaboration.
Sumpradit showed with numbers and data the AMR prevalence, effect of AMR and antimicrobial consumption in Thailand;
According to the article "AMR is resulting in at least 3.24 million additional days in hospital and 38 000 deaths (the authors did not indicate over what period of time. AMR-Times).
- Direct costs of antibiotics to treat AMR infection were about $70-$170m (£54-£132m; €62-€150m; 2400-5800m baht) where Indirect costs of morbidity and premature deaths related to AMR were at least $1100m"
The author presents various Initiatives on AMR in Thailand and their action toward combating antimicrobial resistance and the steps that have been taken in the development of the strategic national plan on AMR on the local and global level including Thailand's contribution to the global agenda on AMR
At last Sumpradit summarize Thailand's national strategic plan on AMR for the upcoming five years, As stated in the article:
- Thailand has actively contributed to setting the global agenda on AMR
- The national strategic plan on AMR (2017-21) promotes multisectoral collaboration to reduce antimicrobial consumption and AMR morbidity and improve public awareness
- Strengthening surveillance systems to measure the burden of AMR and the effect of policies must be a priority"
The article presents a good review of Thailand’s vision and action toward AMR; discusses what has been accomplished and the next action plan that will be implemented in the next 5 years until 2021.
Fostering public as well as private research on AMR in India
In this article, the author Bhabatosh Das and his colleagues discuss R&D of new antimicrobials and rapid diagnostics, as being crucial for tackling AMR in India
At first, Das showed the current case of India by stating risk factors that aggravated the crisis of AMR in India including; high burden of disease, poor public health infrastructure, rising incomes, and unregulated sales of cheap antibiotics. Then, he discussed the vision of the global AMR plan concerning the research field, providing examples about the impact of AMR research and interventions in different countries.
“Overall, we note that insufficient research has been carried out into new interventions and alternatives to antimicrobial treatment. Most research (70% of 1744 studies) has concentrated on new antimicrobial formulations, characterization of antimicrobial properties of known synthetic or natural products, and development of nanoparticle based antimicrobial agents. “
The authors also note that: “There is insufficient research into the mechanisms of resistance and rapid
antimicrobial susceptibility diagnostics, which would provide a better guide to prescribing for treatment of infections.”
Authors were able to arrange the AMR research topics of focus in India demonstrating the impact of different types of researches that have been done on AMR after reviewing and analyzing all published AMR related articles in India, Including researches, reviews, articles, case reports, comments, editorials and new antimicrobials patents.
The authors point to the lack of new antibiotics and rapid diagnostics for AMR and suggest to focus research on surveillance of resistant pathogens.
They notably call for more public research : “Public sector funding for research has been
inadequate owing to lack of awareness of the gravity of the problem and of political will. The national action plan calls for investments in initiatives to contain AMR, but does not make clear what proportion
should be allocated for AMR research”.
This article provides an outstanding overview about AMR research in India; what has been done, how efficient and impactful it was and what areas of focus are required be to be prioritized in the next period.
Stepwise approach for implementation of AMR surveillance in Africa
In this article, published recently in African journal of laboratory medicine, The authors aimed to provide a framework for a stepwise approach toward implementation of laboratory-based surveillance for AMR in African countries.
According to the article "in sub-Saharan Africa, the need for laboratory improvement is evident, with some countries in need of laboratory system built from the ground up. This prevalent lack of laboratory resources and the subsequent difficulty of obtaining accurate results on antimicrobial susceptibility testing is an important challenge to address when proposing a stepwise approach".
The article speaks of the need to establish national Reference laboratories and set the criteria that should be fulfilled in order to ensure the quality of diagnostics for AMR surveillance.
In addition, the authors ensured the importance of assessment of laboratory capacity to perform surveillance for AMR, lab reporting and the possibilities of Laboratory information system in low-middle income countries.
The article provides in a comprehensive prudent way the practical real steps that should be taken to implement AMR surveillance systems in Africa and highlighted important notes that should be considered when designing AMR surveillance plan; It discusses in particular some solutions and recommendations for solving logistical problems and limitations that could take place in the implementation of laboratory-based AMR surveillance, taking in consideration the limited resources problem and the difference in infrastructure preparedness of the countries in the African region.
Pfizer’s release of its position paper
As a follow up for the position papers that Pfizer has been releasing in the past two years since the Davos declaration was signed in January 2016; a new version of Pfizer position paper on Antimicrobial resistance was published one month ahead before prior to the World Health Summit this month (October) 2017 in Berlin, Germany.
Their new position paper focuses on the roadmap for progress on combating antimicrobial resistance
- Reduce the environmental impact of antibiotics production
- Continuous doctors and patient education to ensure the efficient use of antibiotics
- Collaboration with stakeholders with the aim of strengthening healthcare systems
- R&D of new antibiotics, vaccine and diagnostics
Comment by reporter, M. El Ateek : It is instructive to read of pharmaceutical companies and private sector policies through periodical release of their position paper showing their actions on AMR. Of note Pfizer has recently Unveils ATLAS®, An Interactive, User-Friendly Website That Provides Global Antibiotic Resistance Surveillance Data Across 60 Countries.
Book Review: Access to TB and MDR TB in Maputo, Mozambique
Title of the book "Treatment Delays Among Tuberculosis Patients in Maputo
"The aim of this work, was to explore factors that influence services utilization, detection and treatment delays among tuberculosis patients in Maputo, from users and providers side.
Systematic literature review was used, published and unpublished reports accessed. Additionally, discussions with medical staff from the field and those involved in TB programmes in Maputo.
(...) The study found that from provider’s side, there is lack of skilled and motivated staff to diagnose and treat TB. (...) Open hours, services not friendly, lack of confidentiality, stock outs and communication barriers.
Inefficiency of health system and services provision is the most important factor for people mistrusting the public health services.
MoH Initiatives: The government has taken initiatives to improve TB and MDRTB diagnosis and follow up: total health expenditures as a percentage of GDP rose from 2.3% in 1997 to 5.65% in 2009, however still not enough for health sector needs... Abuja commitment was at 15%!
Several poverty related factors are impeding progress.
Main factors are related to the very poor transport infrastructure, meaning it can take half a day for a patient to come seek a treatment dose.
Unsafe housing, poor water and sanitation:
"In Maputo, 70% of the population live in the rural and (urban) periphery called "zona de caniço", due to its composition of precarious material. During the rainy season (Dec to March) houses are filled with water, roads are flooded, making traffic almost impossible. They spend 6 months or more...concerned on how to survive..."
As in other cities in Mozambique :" garbage is not collected, roads are poor, there is poor drainage".
This highlights the vulnerability of the population, to ENVIRONMENTAL pollution and contamination. Unacceptable yet so neglected in the 'AMR era'.
Then, the issue of poor access to medicines:
"When patients are diagnosed, in some cases, there is no drug available to start treatment and for follow up of treatment (...) due to poor management system, poor drug supply..."
In 2014 Maputo (1.5 million inhabitants, 'one of the 15 largest urban areas in sub-Saharan frica) registered 11% lost to follow up (WHO target is 4%)
Then, as elsewhere, there is extremely little attention paid to prevent the risk of contamination in health care settings, Infection prevention and control is a neglected feature of TB management as evidenced by the author's report that:
- Poor or none existent ventilation in consultation cabinets
We note that the book's author does not address the issue of 'dirty' injections estimated to concern 20% of all health care related injections in LMIC selected countries (private communication, POPS, WHO) as this is not mentioned in the book.
A recent survey of unsafe injection practices in the USA itself reported that around 10% of health care staff reported witnessing 'dirty' reuse of material !!
Yet, HIV patients may receive injectable co-trimoxazole for prophylaxis
TB patients make receive injectable streptomycin, and, in case of second line regimen, may receive several injectable drugs.
Use of unsterile procedures in injectable treatment carry a serious risk of transmitting bacterial and viral disease, including ARV-Resistant HIV.
So overall, health staff is not motivated, there is poor materials, poor access to drugs, lack of supervision...
- If health workers' performance may be poor, this is related to poor health care systems in general, health workers are victims of TB and XDRTB as they work in difficult circumstances.
- Difference in gender for TB outcomes: while men are more likely than women to be detected when affected by TB and more likely to start treatment, women, if they effectively access treatment, are more likely to complete treatment and have a lower mortality rate.
A correct diagnosis?
Direct Microscopy, culture, X rays are still in use, while there has been improvements with the introduction of the GeneXpert rapid test providing a sensitive TB diagnosis (including in TB & HIV co-infections) and capacities to identify resistant to Rifampicin and Isoniazid.
MSF is doing a lot to seek to improve the TB detection and cure rate. Home based DOTS with MSF was initiated in 2015. The Dutch government introduced a CheckTB program.
Patient testimony XDR TB due to stockout in public health facilities
"I am a nurse, a civil servant, and I contracted TB in the exercise of my functions. I started treatment Jan 8 2013. In the 3rd quarter of my treatment, the culture was negative and I began to feel better...But (then) there began a lack of meds and then my clinical status went aggravating to the point of being an inpatient in the Hospital of Machava for 8 months. (...) I restarted the treatment with all the meds with MSF but the disease had already progressed to resistance to all drugs..."
In 2013, 23 new cases of XDR TB were identified, one is a health professional. Among those, 8 had died by 2016.
AMR-Times: At this time, the publication of the book should remind everyone that the road to real implementation of UHC is a long one, and, as in the implementation of DOTS treatment, its paper existence should not be confused with REAL health services, real conditions for disease control.
Publisher: Lambert Academic Publishing.
Where to order: order AT morebooks.de ISBN (978-620-2-02515-7)
Nordino I. Sulemane, MPH: Studied International Public Health at Royal Tropical Institute in The Netherlands. With specialization in Health Systems Policy and Management. Champions 8 years of experience in Public Healthcare in HIV and TB/MDR with Doctors Without Borders. Intern in Problem Based Learning, at Superior Institute of Health of Rome, Italy.