Could a food additive be responsible for the rise of C. difficile epidemics? Such is the mind shaking news appearing in Nature this month. Authors correlate the massive introduction of tréhalose as, not only a sweetener, but also a ‘wonder’ product in the industrial food chain in 2000 with the rise in C. difficile, from a study on mice models. Certainly this scientific hypothesis needs serious follow up and more clinical trials. Somehow we found that more mind boggling than the superbugs in UK’s chicken... because anyone informed knew that already! Remember the UK health system telling everyone: don’t wash your chicken! (because that’s throws the bugs all over you and your kitchen!). How are we to avoid trehalose?
Amidst drowning talk on docs and patients having to reduce antibiotics (true, we should, but are we, as individual, the main guilty party? And could we switch the pendulum too far?) the UN Environment Agency puts out a square reminder (prompting a Lancet feature) that AMR arises from the ENVIRONMENT mostly, from all the non treated, improperly treated or improperly recycled waste dumped in rivers: from antibiotics to heavy metals. This short report is a must to read.
From the corner of the eye, we note the very worthy scientific note on how flies have an ‘under-estimated’ disease-carrying potential, and we use the opportunity to say that, in general, the issue of the transmission of AMR infections, the prevention of its spread is much neglected, cognizant that the greater portion of humanity is not enjoying clean and safe care or environment. We can’t protect ourselves from AMR in our backyard.
AMR is high in the news nowadays, making it difficult to keep track. We noted the news on, and from, industry: very high profitability, not too high investments in R&D and, on the good side better clinical transparency. More and more companies are looking into coalitions to do advocacy vis à vis authorities. Meanwhile the US CDC report on Investments, State by State, on AMR!
AMR is at last coming on top of the global agenda, but as Otto Cars stated over the holidays: still too little, too narrow...
Dietary trehalose enhances virulence of epidemic Clostridium difficile
J. Collins and co-authors write that : Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe (...) they « show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence. »
AMR_Times: The study, which appeared in the scientific review Nature, has given rise to quite a few articles in the mainstream press (we give an example). Readers may also note that according to manufacturer CARGILL, trehalose is not only used as a ‘replacement sugar’, but is also used as an additive in preserves and many frozen foods because of its ‘wonder’ properties. See below and website.
Treha™, trehalose wonder product according to CARGILL
Specialty sweetener trehalose
"Trehalose is an ideal ingredient for generating exciting market possibilities for your latest product concepts and also for adding new life to existing food and beverage brands. Trehalose, a diglucose sugar found in nature, confers to certain plant and animal cells the ability to survive dehydration for decades and to restore activity soon after rehydration. This observation has led to the use of trehalose as excipient during freeze drying of a variety of products in the pharmaceutical industry and as an ingredient for dried, baked and processed food, as well as a non-toxic cryoprotectant of vaccines and organs for surgical transplants.
It is especially well suited for sweetening nutritional drinks and other energy products” ...
TREHA™ is a registered trademark of Hayashibara Co. Ltd., used under license
see also, Arstechnica: https://arstechnica.com/science/2018/01/the-curious-case-of-a-boring-sugar-that-may-have-unleashed-a-savage-plague/
and, more importantly: Treha™ On the website of CARGILL. Specialty sweetener trehalose:https://www.cargill.com/food-bev/na/treha-trehalose
C. difficile in Mexico
Impact of Clostridium difficile infection caused by the NAP1/RT027 strain on severity and recurrence during an outbreak and transition to endemicity in a Mexican tertiary care center.
In this study population, C. difficile infection due to ribotype 027 (RT027) was not associated with poorer outcomes, and they recommand molecular epidemiology surveillance. Else the authors stressed the need to avoid use of FQ antibiotics and PPI (which is usual in C diff. Prevention) recommendations.
ABT Resistance and stewardship in ICU, a position statement ESICM/ESCMID/WAAAR
AMR and antibiotic stewardship programs in the ICU: insistence and persistence in the fight against resistance. A position statement from ESICM/ESCMID/WAAAR round table on multi-drug resistance.
De Waele, Jean Carlet et al.
"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. Intensive care and infectious disease specialists from the European Society of Intensive Care Medicine, European Society of Microbiology and Infectious Diseases and World Alliance Against Antimicrobial Resistance, united in the ANTARCTICA (Antimicrobial Resistance in Critical Care) coalition, call for increased awareness and action among 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. Close collaboration with other specialties, and combining these and other interventions in antibiotic stewardship programmes should be a priority in every ICU. Considerate antibiotic use and adopting strict infection control practices to halt 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 our ICUs and continue to treat our patients effectively.
AMR-Times: This issue is especially important in view of the WHO targets to reduce sepsis, globally, in view of the fact that AMR in the ICU is one important aspect of sepsis mortality.
We published the text in Eng and French of ANTARTICA in previous issues of AMR-Times, as the WAAAR Alliance is in the leadership, and we will also report on ANTARTICA in the prestigious yearly AMR Control publication in 2018, to appear in May, both in English and in French.
Web=link: Intensive Care Med. 2017 Dec 19, DOI: 10.1007/s00134-017-5036-1
Groundbreaking: The UN Environment, UNEP: AMR Investigating the Environmental Dimension
The UN report attracts attention to the facts that AMR arises from neglect of the problem of waste in the environment: antibiotics (notably at low level), but also biocides, heavy metals, and biological waste, it reminds readers that bacteria exchange genes, that a wide variety of actions and research needs to be put on track to remedy this fact, and that short of action on the environment, AMR rise will continue unabated.
The report is excellent.
Antimicrobial Resistance: Investigating the Environmental Dimension , Frontiers 2017 report, UNEP
Web=links: http://wedocs.unep.org/bitstream/handle/20.500.11822/22263/Frontiers_2017_CH1_EN.pdf http://www.un.org/apps/news/story.asp?NewsID=58401
The natural environment and emergence of antibiotic resistance
The Lancet attracts attention to the environmental cause of AMR rise, in the wake of the UN agency report.
The article has the merit of pulling alarm bells, even while not totally accurate in its reporting.
The Lancet has a ‘funny’ comment on : Different techniques for removal of antibiotics from the aqueous environment need to be further developed and become not only technical effective but also financially sustainable.
The Lancet Planetary Health has a one page feature on the topic of AMR and the environment.
AMR-Times: It is extremely important that the issue of AMR from the environment, or, should we say, from the neglect of the environment would come to the fore in the global effort against AMR.
We noted a number of errors: the EU banned the use of antibiotics as growth promoters in 2006, but this is not universal. The article writes on the problem of ABT release into the environment but does not mention the release of biological material containing drug resistant bacteria (either from food production or hospitals)
It references the excellent UN Environment Program report on AMR.
We noted the emphasis on research for new and better ways to recycle waste from industrial production.
Imipenem–Relebactam and Meropenem–Vaborbactam: Two Novel Carbapenem-β-Lactamase Inhibitor Combinations
George G. Zhane et all. The authors write: “In conclusion, relebactam and vaborbactam serve to broaden the spectrum of imipenem and meropenem, respectively, against β-lactamase-producing Gram-negative bacilli. The exact roles for imipenem–relebactam and meropenem–vaborbactam will be defined by efficacy and safety data from further clinical trials. Potential roles in therapy for these agents include the treatment of suspected or documented infections caused by resistant Gram-negative bacilli-producing ESBL, KPC, and/or AmpC β-lactamases. The usage of these agents in patients with CRE infections will likely become the standard of care. Finally, increased activity of imipenem–relebactam against P. aeruginosa may be of clinical benefit to patients with suspected or documented P. aeruginosa infections. “
Clinical impact of the Xpert Ultra: new modeling study
Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study.
The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance.
In summary, (the authors say) Xpert Ultra holds promise as a rapid and highly sensitive test for tuberculosis case detection and simultaneous detection of rifampicin resistance. Its sensitivity gain compared with Xpert is most apparent in individuals with low sputum bacillary burdens. Implementation approaches will need to consider the effect of possible false-positive Xpert Ultra results.
Study carried out with collaboration from FIND, Foundation for Innovative Diagnostics
On profitability of drug making
According to a new GAO report, covered by the publication STAT: From 2006 to 2015, the drug industry's revenues rose by 45 percent. And the pharmaceutical R&D spending increased by 8.5%...
Web=links: Several articles on STAT: https://www.statnews.com GAO: https://www.gao.gov/products/GAO-18-40
Measuring clinical trial transparency:
Clinical trials: An empirical analysis of newly approved drugs and large pharmaceutical companies
An important score card study on clinical trials, raking companies.
Flies' disease-carrying potential may be greater than thought
A study initiated at Penn State’s Eberly College of Science shows that houseflies and blowflies carry and spread a variety of species of bacteria that are harmful to humans. "Flies' disease-carrying potential may be greater than thought, researchers say"
AMR Times: Very important to read! At last, more attention paid to a mechaniscal transfer for travel of pathogens, notably virus and bacteria. Which is different from a situation where the pathogene is transfered biologically (malaria, trypanosomiasis). Such differences were identified by the first Pasteurians doing research in developing countries. The issue of 'transmission' in AMR tends to be underplayed and underfunded. In this domain, it is clear that in poor countries flies will play a role in transmitting 'mechanically' drug-resistant bacteria and virus.
IPC rising on the agenda?
In AMR-Times we keep deploring the small attention paid to the urgency of strengthening or setting up strong solid infection systems. We had a brief exchange with WHO Afro region Director Pr Moeti during a break at the Executive Board of the WHO, Nov 24rth and happily report that she fully agreed; to combat AMR, more attention more investments are needed to build solid infection control systems in health care on the continent, considering that few facilities in few countries have such systems in place in Sub-Saharan Africa.
We noted a "Euractive Round Table "Radical Hospital Hygiene reform needed in Europe", a worthy title, but the moderator's comment did not indicate much familiarity with this issue as he stated that "Scientists need evidence" (??): if mainstream media ‘believes’ that the evidence for AMR infection transmission is lacking, we’re in trouble!
US CDC publish map of investments in AMR
Today CDC released new data in its Antibiotic Resistance (AR) Investment Map showcasing CDC’s activities to slow antibiotic resistance and meet national goals. These are the first comprehensive reports on state progress made following the first year of Congress’ unprecedented investment in CDC’s Antibiotic Resistance Solutions Initiative.
The AR Investment Map features more than 170 state-reported successes, like rapidly identifying and containing rare and concerning resistant germs to protect communities, and printable state- and city-specific fact sheets that describe how CDC invest in activities in that area. In the fiscal year 2016, CDC made investments in all 50 states, six large cities, and Puerto Rico to enhance laboratory and epidemiology expertise and to grow public health innovations to fight antibiotic resistance across healthcare settings, food, and communities.
As Malaria Resists Treatment, Experts Warn of Global Crisis
The New York Times Nov 21, 2017
GAVI: Why do Vaccines work against antibiotic resistance?
GAVI's Ciarra Mac Carthy develops a few arguments, and notably points ot the "sophistication of how vaccines defend against bacterial infection. Antibiotic drugs tend to act by targeting one specific bacterial protein or mechanism. In some cases, just one mutation could be enough to alter the target so that it is no longer recognised by the drug – making the bacteria resistant. By contrast, some vaccines can expose the immune system to a huge number of bacterial proteins. This promotes the development of a vast repertoire of antibodies that uses a large number of lines of attack to prevent bacterial infection. The chances of the bacteria simultaneously evolving resistance to attack from every type of antibody produced is slim. "
She goes on to point out that: "Vaccination can help to combat overuse by preventing infections that would otherwise require antibiotic treatment and help curb the spread of resistant strains. They also provide a crucial defence against diseases that can no longer be treated with antibiotics."
New WHO ADG on AMR
WHO announcement: Dr Ranieri Guerra, MD, from Italy, has been appointed Assistant Director-General for Special Initiatives, which includes antimicrobial resistance (AMR), polio and polio transition
AMR-Times: What has polio got to do with AMR? Perhaps get the Rotaries to fund AMR globally, would be a good idea!
WAAAR member organizes major patient safety congress in Benin, CIMSA 2018
Dr Frank Mansour Adeoty, WAAAR member in the Ivory Coast and leader of the RIPAQS Africa organization is, again, organizing a major event in West Africa: the CIMSA. Frank has been a tireless organizer of training in the the RCI and neighboring countries with one event a year! Further a few years ago, under the leadership of Dorothée K Gazard, then Minister of Health, and the organizing power of Frank and the RIPAQS, the first CIMSA was held in Cotonou. For the first time, the issue of patient safety brought together Ministers of Health, directors of health services from more than a dozen African countries, civil society, NGOs and the private sector to discuss for a week all the elements needed for real patient safety implementation focusing on mother-child health.
This year, the focus with include e_Health and new tools, around the themes of AMR and the needed improvement in health care delivery.
Website of CISMA 2018: www.africa-cimsa.com
RICAI 2017 : Inter-disciplinary meeting of anti-infective chemiotherapy
Session on Urinary Track infections.
Report by Pr Nora Mahfouf
Community urinary infection and adequacy of antibiotic therapy: impact of targeted antibiogram
In order to limit the use of critical antibiotics such as third generation, cephalosporins, Augmentin and fluoroquinolones, and for good ABT stewardship, the research done by Dr Céline Michelangelii (general practitioner, Nice) had the purpose to see if the establishment of a targeted antibiogram for cytobacteriological urine examinations (ECBU) has an impact in terms of ABT prescription. She found that within the limits of the number of cases studied, the impact of targeted antibiograms is 28%. She concluded that the targeted susceptibility test may be of interest in urinary tract infections requiring ECBU and follow-up.
Impact of an FQ savings policy on resistance at E.coli:
results of ten years of actions carried out in a French local hospital.
The strong prescription and the excessive use of fluoroquinolones (FQ, major class of antibiotics in human therapy) led to a strong bacterial resistance against this class. The study of Dr. Allison Muller, University Center Morteau, Besançon had the objective of establishing a policy to reduce the FQ of the institution on city prescriptions.
The study follows the use of ABT in general and FQ in particular in the establishment, and the resistance of E coli to these. Then it was to follow the evolution of sales of FQ in a local pharmacy. Successful study: Strong involvement of practitioners (doctors / pharmacist / biologist) of the establishment in this policy of good use ATB, reduction of sales of FQ in a Morteau pharmacy and increased sales of fosfomycin and nitrofurantoin which led to a reduction in resistance to nalidixic acid in E. coli (-57%) visible 5 years after the start of the decline in FQ. Increased from one of the strongest FQ consumers to the smallest consumer in the region, with a drop of 86% in FQ consumption. Its FQ consumption has fallen below the median FQ consumption of comparable establishments. At the same time, there was a significant drop in the number of ECBUs (-62% between 2008 and 2016) and less risk of prescription of ATB treatments for urinary colonization.
Program of good use of antibiotics in health facilities (ES) since the early 2000s:
As part of a program of good use of AB in French health facilities (ES), the Ministry of Health uses specific indicators that reflect the level of commitment of the health facility, in a health strategy. The Optimization of the effectiveness of antibiotic treatments. The indicator of good use of AB (ICATB): is a set of organizational criteria (policy, access advice and alert), resources (IT, human and training) and actions (prevention, monitoring and evaluation / audit ).
According to the communication of Dr. Catherine Dumartin, Bodeaux, the ICATB.2 is a 2nd generation indicator based on the progress observed between 2006 and 2012 with "ICATB1", it shows the organization set up in the establishment to promote the proper use of antibiotics, the means it has mobilized and the actions it has implemented. This good use combines objectives of individual benefit for the patient (best possible treatment) and collective (limitation of the emergence of resistant bacteria), and proposes new criteria: Multidisciplinarity of the organization, resources and skills dedicated, restrictive measures: reassessment, justification of treatments and communication of monitoring and audit results.
Shortage of anti-infectives and vaccines: what is the reason? What answers?
The shortage of anti-infectives and vaccines, is a problem that can have consequences on several sectors: pharmaceutical, medical and economic. To improve the situation in a sustainable way, the French National Academy of Pharmacy proposes to consider the pharmaceutical industry in France as a strategic sector, to make an analysis of the ASMR report / cost of the product portfolio by starting the oldest and finally, put in place a better coordination between all the actors to anticipate the long-term actions and to accompany them. In the case of vaccines, the academy proposes harmonizing vaccination schedules and eliminating duplicate batch release controls, and prohibiting the export of declared out of stock or risk of stock-outs by ANSM.
To avoid stock-outs, new requirements have been proposed:
At the level of the laboratories: the assurance of an appropriate and continuous supply of the national market so as to cover the needs of patients in France, taking any useful measure to prevent and overcome any difficulties in supply, and finally the setting up of permanent emergency call centers.
Regarding wholesaler-distributors: the provision in the territory of 14 days of stock and a quota of medicines containing at least 9/10 th of the presentations of specialties registered in France, the establishment of a system of reserves to meet the urgent needs of drugs and the immediate information system for the laboratory of any rupture in supply.
Alternative measures are also desirable, such as information for health professionals and patients, qualitative and quantitative quotas, the setting up of a safety stock and finally the solicitation of competing laboratories with medicines containing the same active substance(s) by increasing production and allocating additional stocks
Risk Communication and Ebola-Specific Knowledge and Behavior during 2014–15 Outbreak, Sierra Leone
Study ssessed the effect of information sources on Ebola-specific knowledge and behavior during the 2014–15 Ebola virus disease outbreak in Sierra Leone, pooled data from 4 population-based knowledge, attitude, and practice surveys (August, October, and December 2014 and July 2015), with a total of 10,604 respondents. (..) "In conclusion, the results of this study show the importance of information sources in influencing knowledge and behavior—in both positive and negative directions—and could be used for communication strategies in emergency preparedness and disease outbreaks in low-income settings. Our findings underscore the value of risk communication for rapid disease control efforts and, therefore, for global health security."
First International Conference on Global Health Security:
Progress to date, Opportunities for the future. Sydney, Australia
18-20 June 2019
In the wake of the 2014 West African Ebola outbreak, the international spread of Zika, the ongoing
transmission of antimicrobial resistance, and the ever-present threat of another influenza pandemic, global health security has taken on a new level of importance. Multiple commissions and high-level panels have been held, recommendations have been issued, and governments, international organisations, civil society and private industry have all committed to various initiatives aimed at improving health outcomes. Even so, significant challenges remain.
The conference will have several objectives:
• Bring together stakeholders working in global health security to measure progress,
determine gaps, and identify new opportunities to enhance national, regional and global
• Provide a venue for government officials and International Organizations to share policy
developments, hear from the research committee, and create a space for side meetings that
advance the health security agenda.
• Establish and solidify a health security ‘community of practice’ and guiding principles;
• Through an open call for abstracts, highlight work from partners around the world, bringing
cutting edge, evidence-based research to the community;
• Provide an opportunity for students to showcase their research;
• Consider creating a professional association for global health security; and
• Create a venue to consider the development of a declaration on global health security.
We are at a critical juncture in the field of global health security and it is appropriate to organize the community around a set of common principles, goals and objectives. Like the London Declaration for Neglected Tropical Diseases or the Oslo Guidelines on civil-military cooperation, this conference could bring together the global heath security community to agree on a set of principles to guide the field and set priorities. (briefing from the organisers to AMR-Times)