Nov 9 WHO consultation on the "Global Framework for Development and Stewardship", Draft Roadmap
The meeting opening was presided by one of the ADGs in the new team, the Brazilian Dr. Mariângela Batista Galvão Simão, Assistant Director General for Drug Access, Vaccines and Pharmaceuticals. The moderator was the director in the same department Dr Suzanne Hill.
Marc Sprenger, Director AMR Secretariat noted that controlling AMR is needed to achieve the SDGs worlwide, an opinion supported by REACT and ICGAR (Interagency Coordination Group on AMR) representative in attendance Pr Otto Cars.
At present 92 national AMR programs exist today and 60 countries are preparing one.
All Member States should do their own campaign.
A program on Behavior modification is being elaborated by the WHO in collaboration with the Wellcome Trust.
The surveillance and monitoring program GLASS is progressing in countries, notably French speaking Africa lately.
There are very wide differences in antibiotic use in food-producing animals, and on Nov 7th the WHO released the "Guidelines on Use of Medically Important Antimicrobials in Food-Producing Animals". Dr Awa Aidara Kane, chair of AGISAR, said Sprenger, spend two years working with experts (including representation from the OIE and FAO), and a thorough review of evidence to develop these Guidelines.
Marc Sprenger went on to say that WHO can only make recommendations, it is in governments' hands whether to implement or not.
He recalled WHO work on infection prevention and control (IPC), with the release of the guidelines on CRE and CP, and the elaboration of the target listing of bacteria.
He went on to stress the importance of civil society participation, mentioning the EPN, Ecumenical Pharmaceutical Network as important collaborators.
The Netherlands representative congratulated the WHO on the Guidelines, adding that they were "very pleased because NL secong largest exporter of meat, and we encourage people to read the guidelines".
The UK thanked the WHO for these Guidelines, saying "we met our targets two years early" Sprenger noted that the UK reduced antbiotic animal consumption by 70% while increasing production by 11%
Brazil expressed reservations and said they were surprised by guidelines on animals.
Dr Kazuaki Miyagishima, Director of the WHO's Department of Food Safety and Zoonoses, strongly backed up the Guidelines.
Several Member States asked why and how the WHO had set a target of 10% reduction in Sepsis death due to AMR?
The Sub-secretariat for Multilateral Affairs and Human Rights General Directorate for Global Issues wrote, and the head of health at the Mexico Mission to the UN intervened to state that: “Mexico recognizes the multifactorial causes of AMR, which implies the need for inter-institutional response from the fields of health, food and livestock, the pharmaceutical and chemical industry, medical training and timely information to the population in general, as well as the integral management of drug residues in particular of antibiotics.” (...)
In line with the World Plan of Action adopted within the World Health Organization through resolution WHA68.7, Mexico considers that the global response should include:
a) Education, training and dissemination; b) Health regulation and surveillance; c) Prevention and control; d) Research and e) Financing.”
Mexico objected to the Framework being limited to objectives 4 & 5.
The Framework in details
Dr Peter Beyer, Senior Advisor, Department of Essential Medicines & Health Products, presented in details the Framework on Stewardship proposed, from the discussion on a "global R&D funding mechanism", to Priority pathogens for R&D: He stressed that there are "Insufficient innovative products in the pipeline : 10 products in phase one, only 1 or 2 will make it in seven years. So a big crisis coming."
There was also the need to prioritize vaccines both in animal health (a topic recently underlined by the PACCARB meeting). And the much needed R&D for in vitro diagnostics for AMR.
Beyer spoke of the importance of the GARDP initiative, Jean-Pierre Paccaud, GARDP Incubation Business Development & Strategy Director, DNDi was in the room.
Another discussion was on Access, where it was emphasized that there are shortages in production of basic generic older antibiotics, a situation which needs to be remedied. There are basically three groups of antibiotics: the basic ones where generics predominate 'Access', those of the 'Watch list' and those in the 'Reserve group' (antibiotics of last resort). What is put forth as the AWARe model: Access, Watch and Reserve.
There are also regulatory issues, including work on the regulation of pharmaceutical marketing, and the issue of transparency in costs and prices. "The Framework should cover the whole value chain." said Peter Beyer.
In R&D the Framework ambitions to be setting priorities.
1-"Prioritization of human pathogens to guide R&D of new antibiotics."
The WHO report on prioritization of pathogens for R&D has identified 12 classes of priority pathogens (critical, high and medium priority", along with M. tb.
The WHO published an analysis of the pipeline in Sept 2017 which shows it's rather empty. More importantly, it is supporting a PoC (Rapid Point of Care) Diagnostics R&D effort.
2- Priority list of animal disease for vaccine development.
With the OIE (2015) priorities were set for chicken, pigs and fish.
AMR-Times notes that The PACCARB proposal, very recently to create an Innovation Institute for Animal Health, notably to better understand immunity across species, might be useful for better basic scientific understanding.
Several speakers noted the absence of mention of needed research in the microbiome, in human or animal species.
3-Measures to reduce antibiotics as growth promoters. Banned in 2006 in the EU, they are still not banned in the US (only the FDA put out voluntary guidelines) and much of the emerging countries, and the US opposition to the new WHO Guidelines for Food-producing Animals may not help.
The Framework mentions good husbandry and housing practices, biosecurity, rigorous disease control measures...but will not apparently seek to elaborate on these.
4- Diagnostics and AMR Surveillance, refers to OIE and FAO manuals.
5- GARDP: an R&D initiative for global public health needs. GARDP is a DNDI-WHO intiative, 56.5 million US Dollars in pledges from Germany, Luxemburg, the Netherlands, the UK and the Wellcome Trust.
GARDP will co-develop Zoliflodacin for drug-resistant gonorrhoea and is working on neonatal Sepsis, said J-P Paccaud.
Mention was made of the German G20 launch of the Global AMR R&D Hub.
Link to UN group:
Interagency Coordination Group on Antimicrobial Resistance
WHO Guidelines on the use of Medically Important Antimicrobials in Food-Producing Animals
The Guidelines, put together under the leadership of WHO's AGISAR (Advisory Group of Integrated Surveillance for AMR), Chaired by Pr Awa Aidara Kane, worked over a two year period for this publication, and brought together a wide array of experts, including representation from the OIE (Elisabeth Erlanger-Vindel) and FAO (Henk Jan Ormel), while being a distinct WHO publication.
The Guidelines recall the UN commitment to work on a 'One Health' approach and the fact that many antimicrobials used in food-producing animals – as well as in plant production, including orchards - are identical or closely related to AM used in humans. AM are used to treat sick animals, but are also used as growth-promoters (whenever they have not been banned – the EU forbade them in 2006 in the EU, the FDA recommended to phase them out, but did not yet forbade their use), or used in prophylaxis for prevention These usages can lead to "selection and dissemination of AMR bacteria in food-producing animals, which can then be transmitted to humans via food and other transmission routes." (water and soil, notably – AMR-Times).
The Guidelines uses the CIA (Critically Important Antimicrobials) list, which CIA guidelines last came out recently, as the basis for its recommendations. At the Framework meeting, Pr Kane said no more CIA list will be issued from the WHO in the future, because of the changes in the guidelines system.
The Guidelines on the use of medically important AM in food-producing animals took two full years to assemble because of the need to gather as much scientific evidence as could be identified on this interaction.
The Guidelines recommend:
- An overall reduction in use of all classes of medically important AM in food-producing Animals
- Complete restriction of use of all classes of medically important AM in food-producing animals for growth promotion
- Complete restriction of use of all classes of medically important AM in food-producing animals for prevention of infectious diseases that have not yet been clinically diagnosed
In case of the presence of disease, the Guidelines recommend:
- AM classified as critically important for human medicine should not be used for control of the dissemination of a clinically diagnosed infectious disease identified within a group of food-producing animals.
- Suggest that AM classified as highest priority critically important for human medicine should not be used for treatment of food-producing animals with a clinically diagnosed infectious disease.
They include a remark that however this can be overruled depending on the best judgment of a veterinarian, when bacterial culture and sensitivity results show that the selected drug is the only treatment option.
Basically, the approach is from the 'precautionary principle' (more in use in Europe than in the USA as a principle). The Guidelines document says the recommendations should be 'conditionals' because of the low quality of evidence, so far.
However, implementing these restrictions carries no undesirable consequence or hardly, and 'several countries have successfully accomplished such a restriction, demonstrating its feasibility."
Best practice statements:
1- Any new class of AM or new AM combination developed for use in humans will be considered critically important for human medicine unless categorized otherwise by WHO
2- Medically important AM that are not currently used in food production should not be used in the future in food production (animals or plants)
The rationale is that a number of medically important AM not currently used in food production are AM "of last resort" for humans... carbapenems, oxazolidinones (e.g.linezolid), and lpopeptides (e.g. daptomycin). Preserving these for human use is best practice.
Development and marketing of new classes of AM for humans is likely. (...)
They note further that these best practices are consistent with the OIE statement that "AM classes/sub-classes used only in human medicine are not on the OIE list of Antimicrobials of Veterinary Importance (OIE list).
(we used AM for antimicrobials and other abbreviations consistent with the need to compress the length of an email newsletter- AMR-Times)
In the beginning, with Recommendations
The Guidelines notably justify writing that : Extensive research into mechanisms of AMR, including the important role of horizontal gene transfer of AMR determinants, supports the conclusion that using AM in food-producing animals select for AMR in bacteria isolated (in these) animals, which then spread among them, into their environment, and to humans. Furthermore systematic reviews concluded that broad restrictions covering all AM classes appear to be more effective.. compared to narrow restrictions, even though there are examples of marked reductions in AMR following restriction of a single AM. Finally this is in agreement with the GAPAMR.
The Guideline document does not mention ways and means to decrease the need for AM by improving the living quarters of the animals or its hygiene.
AMR-Times: Overall the Recommendations of the Guidelines appear medically sound in view of the danger posed to human health of AMR spread, which have been amply documented by the AMR Review and other expert bodies reviewing scientific evidence. Considering that the greater share of antibiotics use is in agriculture, and notably in food producing animal, the PRECAUTIONARY principle is understandable. Now, since PPP have arisen and a global effort has been mounted to help industry being new products to market, while sales would be limited for human medicines ("Reserve" class to use the Framework term), one may hypothesis that the anger at the Guidelines would come from economic interest. If implemented by all countries, these Guidelines would decrease sales now and freeze income expectations on sales of new products if these antibiotics were restricted in human health but not in agriculture.
Since AMR infections are obviously on the rise among food-producing animals, the temptation will increase to use latest state of the art products whose sale price could be quite high, and the decoupling would apply to volumes but not prices.
Now why is the agricultural sector reluctant to cut costs in purchases of antibiotics?
Other unrelated source materials on this issue:
Center for Science in the Public Interest : Antibiotic Resistance in Food-borne Pathogens.
This report details antibiotic‐resistant food-borne outbreaks from 1973 to 2011. In total, 55 outbreaks were identified (sickened 20,601 individuals, of whom 3,166 required hospitalization and 27 died ). Food items most likely associated with antibiotic resistant pathogens included dairy products, ground beef, and poultry. These three food categories were implicated in more than half of reported outbreaks (31 of 55). Salmonella spp. was the most common cause of antibiotic‐resistant outbreaks identified (48 of 55). Pathogens exhibiting multi-drug resistance to five or more antibiotics were identified in more than half of the outbreaks (31 of 55, 56%)
Meat producers against WHO guidelines, Web=links: http://www.tipperarystar.ie/news/home/280602/tipperary-farming-factual-evidence-must-support-decisions-on-antibiotic-use-in-animals-says-ifa.html
Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis, Web=links:
Costs and Benefits of Antimicrobial Use in Livestock, Aude Teillant, Web=links: http://www.globalhealthdynamics.co.uk/wp-content/uploads/2015/05/19_Aude-Teillant.pdf
Survey details spread of livestock-associated MRSA in Europe
"Results from a survey published yesterday in Eurosurveillance indicate more frequent detection and greater geographical dispersion of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in Europe.
The survey and questionnaire from the European Centre for Disease Prevention and Control (ECDC) collected data on LA-MRSA subtypes identified among MRSA isolates by national or regional reference laboratories in European Union/European Economic Area (EU/EEA) countries in 2013. The samples included both clinical and screening isolates. Overall, 28 reference labs (26 national and 2 regional) from 27 of 30 EU/EEA countries responded.
The respondents reported receiving MRSA isolates from 14,291 patients in 2013, of which 13,756 (96.3%) were molecularly typed. LA-MRSA was identified by 17 of 19 countries (89%) with MRSA typing data. The Netherlands, Denmark, and Spain reported the most LA-MRSA isolates (164, 157, and 52, respectively). The overall percentage of typed MRSA isolates that were LA-MRSA was 3.9% (535 of 13,756).
Almost all LA-MRSA isolates belonged clonal complex (CC) 398, which is commonly associated with swine and is the most widespread MRSA lineage in Europe. The only non-CC398 subtype considered to be LA-MRSA came from Italy.
This was the first survey conducted on LA-MRSA in the EU/EEA since 2007, when only eight countries reported LA-MRSA isolates from human; in that survey, the proportion of MRSA that were LA-MRSA was above 2% in four countries and one region of Germany. The authors of the current study say the 2013 survey results, along with more recent data suggesting that LA-MRSA is spreading in the Nordic countries, the Netherlands, Germany, and the UK, indicate an apparent upward trend and more widespread dispersion of LA-MRSA across Europe. They're also concerned that labs in seven of the responding countries did not report any MRSA typing.
The ECDC is recommending that EU/EEA countries repeat the survey periodically to monitor for changes and map potential reservoirs and transmission pathways.
Nov 2 Eurosurveillance report
Nov 3 ECDC news release
Livestock-associated meticillin-resistant Staphylococcus aureus (LA-MRSA) among MRSA from humans across the EU/EEA, 2013: ECDC survey
WHO initiated a mobilization on IPC on the occasion of the antibiotic awareness week
As presented by Director AMR at WHO, Dr Marc Sprenger
- New infographic on the role of IPC in preventing antibiotic resistance in health care (http://www.who.int/infection-prevention/en/)
- Online publication of a Lancet Global Health Commentary on 10 November on national and global priorities for IPC, authored by WHO, US CDC, and informed by the WHO’s Global Infection Prevention and Control Network (GIPCN)
- Launch of the new WHO Guidelines for Carbapenem-resistant Enterobacteriaceae (CRE), Carbapenemase-producing (CP) Pseudomonas aeruginosa and Acinetobacter baumannii during WAAW
- Presentation on these new guidelines by Professor Lindsay Grayson (Austin Health and University of Melbourne, Australia) on 13 November 2017 through Webber Training
Strengthening IPC and systematic surveillance of HAIs in India
Analysis Antimicrobial Resistance in South East Asia
"Establishing and expanding government led networks to strengthen infection prevention and control and healthcare associated infection surveillance are essential to effectively tackle antimicrobial resistance. Soumya Swaminathan and colleagues discuss the progress in India"
Dr Soumya Swaminathan (the director of the Indian MRC, now DDG WHO). Systems, policies, and procedures to measure and prevent healthcare associated infections are essential for a comprehensive response to antimicrobial resistance, write the authors who propose surveillance of HAI as to 'drive the implementation of evidence-based IPC'.
The wording is very important, because too often, even in the WHO programs, 'surveillance' is put in a different box, in a different implementation stream than IPC. And this can lead to just 'northern' experts traveling in LIC to take samples from patients and reporting back on bacterial resistance, even reporting on the national authorities. Here we are obviously talking about outbreak investigations and enlisting the health carers as a team to understand what went wrong and to implement better infection control measures.
Soumya and colleagues write that "The quality and consistency of surveillance data on healthcare associated infections are limited in India"
"Ministry of Health agencies in India, with support from the CDC, are implementing healthcare associated infection surveillance that is tied to strengthening IPC practices and characterizing AMRpatterns."
"In India, and elsewhere in South East Asia, government led initiatives can be used to advocate for and prioritize commitment and funding to sustain healthcare associated infection surveillance and infection prevention and control programs.
"The models developed and lessons learned in implementation and expansion of HAI surveillance and IPC capacity building in India apply to other countries in South East Asia that also have a mix of public and private sector facilities, higher capacity referral centers in urban areas, and a large number of resource constrained healthcare facilities in both urban and rural areas. (This)...will improve the detection and prevention of AMR in India and other countries in the region. "
Web=lien: BMJ 2017; 358 doi: https://doi.org/10.1136/bmj.j3768
Hospital architecture's role in prevention of AMR infection spread
Hospitals should design premises and adapt their infection control routines to a society that no longer has effective antibiotics, and that is vulnerable to fast spreading global pandemics. This is argued in a new dissertation from Lund University in Sweden, and was used to build a hospital accordingly in Sweden.
"Many hospitals in Sweden and the world are becoming old and worn out. ... (we had) the chance to build properly from an infection control point of view", says Torsten Holmdahl, doctoral student at Lund University and medical consultant at the infection clinic at Skåne University Hospital.
High level of Syringe reuse in US Hospitals
A study conducted by the US Centers for Disease Control, CDC, found that "12% of physicians and 3% of nurses indicated syringe reuse occurs in their workplace”, and that in general “Unsafe injection practices were reported by both surveyed physicians and nurses.”
They conclude that action is needed to remedy this situation!!
American Journal of Infection Control Vol 45 issue 9 pages 2018-1023One needle, one syringe, only one time? A survey of physician and nurse knowledge, attitudes, and practices around injection safety, by Rachel Kossover-Smith et col.
Other news roundup:
Dame Sally Davies in the Guardian
"We need some real work on the ground to make a difference or we risk the end of modern medicine.”
She added: “Not to be able to effectively treat infections means that cesarean sections, hip replacements, modern surgery, is risky. Modern cancer treatment is risky and transplant medicine becomes a thing of the past.”
Davies said that if the global community did not act then the progress that had been made in Britain may be undermined.
She estimated that about one in three or one in four prescriptions in UK primary care were probably not needed. “But other countries use vastly more antibiotics in the community and they need to start doing as we are, which is reducing usage,” she said. “Our latest data shows that we have reduced human consumption by 4.3% in 2014-15 from the year before.”
Facing the challenges of and providing solutions for antimicrobial resistance (AMR) in the intensive care unit. A call for action from the ANTARCTICA (ANTimicrobiAl Resistance CriTIcal CAre) – coalition.
Brussels, 15 November 2017. Today, intensive care and infectious disease specialists from the European Society of Intensive Care Medicine (ESICM), European Society of Microbiology and Infectious Diseases (ESCMID) and World Alliance Against Antimicrobial Resistance (WAAAR), united in the ANTARCTICA (ANTimicrobiAl Resistance CriTIcal CAre) – coalition, call for increased awareness and action among intensive care and infectious diseases health care professionals to reduce AMR development in critically ill patients, to improve treatment of AMR infections and to coordinate scientific research in this high-risk patient population.
AMR is a clear and present danger to patients in any intensive care unit (ICU) around the world. It is associated with increased mortality, prolonged length of stay, increased costs and paradoxically, increased antibiotic use. Studies indicate that at least 25.000 patients die each year of AMR in the hospital, many of them in the ICU. The number of patients affected by and dying from AMR infections in Europe is expected to increase significantly in the next years; by 2050 an estimated 390.000 patients will die from AMR in European countries.
Whereas AMR may affect any patient in the hospital, patients in the ICU are particularly at risk of acquiring AMR infections due to the intensity of the treatment, use of invasive devices, increased risk of transmission and exposure to antibiotics. AMR is present in every ICU, although prevalence is geographically different and AMR pathogens encountered are variable. In Southern and Eastern Europe, the Middle East, and many countries in Asia, AMR is a daily challenge, with often limited options for antibiotic therapy.
Despite this threat, we are confident that we can turn the tide on AMR in our ICUs because of a number of reasons:
- Knowledge about the mechanisms involved in the development and spread of AMR is increasing.
- Technologies to rapidly diagnose infections and document the involvement of AMR pathogens are becoming available.
- New antibiotics particularly aimed at AMR pathogens are becoming available and many are under investigation. In parallel, non-antibiotic strategies to treat severe infections are under development.
- The importance of infection control in hospitals is now recognized and infection control programs are increasingly effective in controlling the spread of AMR infections.
In order to consolidate this knowledge, the Coalition against antimicrobial resistance in critical care has identified priorities in four domains to improve AMR infection management in the ICU (figure 1) and urges healthcare professionals, scientific societies and industry to take action.
This will require concerted, multifaceted and continued action from healthcare professionals as well as all stake holders involved including patient organisations, scientific societies, pharmaceutical industry, health care policy makers and politicians. We are aware that the same threat applies to low income countries where unfortunately some of the high-technological options may not be available. Nevertheless, we are confident that the other low-cost components also apply and may help to reduce the burden of MDR in these countries. In the ICU, tackling AMR remains a responsibility shared by all healthcare workers, from physicians to maintenance personnel, from nurses to physiotherapists, from consultants to medical students. Together, we can reduce AMR in the ICU, and continue to treat our patients effectively.
References: AMR Control 2017
A Global Declaration on Appropriate Use of Antimicrobial Agents across the Surgical Pathway
A declaration by the Global Alliance on Infections in Surgery
This declaration, signed by an interdisciplinary task force of 234 experts from 83 different countries with different backgrounds, highlights the threat posed by AMR and the need for appropriate use of antibiotic agents and antifungal agents in hospitals worldwide especially focusing on surgical infections. As such, it is our intent to raise awareness among healthcare workers and improve antimicrobial prescribing. Tofacilitate its dissemination, the declaration was translated in different languages.
www.liebertpub.com/sur. (for other languages)
In AMR Control 2017,
Dr Massimo Sartelli, Global Alliance on Infections in Surgery