Céline Pulcini

Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis

BACKGROUND The spread of antibiotic-resistant bacteria poses a substantial threat to morbidity and mortality worldwide. Due to its large public health and societal implications, multidrug-resistant tuberculosis has been long regarded by WHO as a global priority for investment in new drugs. In 2016, WHO was requested by member states to create a priority list of other antibiotic-resistant bacteria to support research and development of effective drugs. METHODS We used a multicriteria decision analysis method to prioritise antibiotic-resistant bacteria; this method involved the identification of relevant criteria to assess priority against which each antibiotic-resistant bacterium was rated. The final priority ranking of the antibiotic-resistant bacteria was established after a preference-based survey was used to obtain expert weighting of criteria. FINDINGS We selected 20 bacterial species with 25 patterns of acquired resistance and ten criteria to assess priority: mortality, health-care burden, community burden, prevalence of resistance, 10-year trend of resistance, transmissibility, preventability in the community setting, preventability in the health-care setting, treatability, and pipeline. We stratified the priority list into three tiers (critical, high, and medium priority), using the 33rd percentile of the bacteriums total scores as the cutoff. Critical-priority bacteria included carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, and carbapenem-resistant and third-generation cephalosporin-resistant Enterobacteriaceae. The highest ranked Gram-positive bacteria (high priority) were vancomycin-resistant Enterococcus faecium and meticillin-resistant Staphylococcus aureus. Of the bacteria typically responsible for community-acquired infections, clarithromycin-resistant Helicobacter pylori, and fluoroquinolone-resistant Campylobacter spp, Neisseria gonorrhoeae, and Salmonella typhi were included in the high-priority tier. INTERPRETATION Future development strategies should focus on antibiotics that are active against multidrug-resistant tuberculosis and Gram-negative bacteria. The global strategy should include antibiotic-resistant bacteria responsible for community-acquired infections such as Salmonella spp, Campylobacter spp, N gonorrhoeae, and H pylori. FUNDING World Health Organization.

The impact of infectious disease specialists on antibiotic prescribing in hospitals.

Given the current bacterial resistance crisis, antimicrobial stewardship programmes are of the utmost importance. We present a narrative review of the impact of infectious disease specialists (IDSs) on the quality and quantity of antibiotic use in acute-care hospitals, and discuss the main factors that could limit the efficacy of IDS recommendations. A total of 31 studies were included in this review, with a wide range of infections, hospital settings, and types of antibiotic prescription. Seven of 31 studies were randomized controlled trials, before/after controlled studies, or before/after uncontrolled studies with interrupted time-series analysis. In almost all studies, IDS intervention was associated with a significant improvement in the appropriateness of antibiotic prescribing as compared with prescriptions without any IDS input, and with decreased antibiotic consumption. Variability in the antibiotic prescribing practices of IDSs, informal (curbside) consultations and the involvement of junior IDSs are among the factors that could have an impact on the efficacy of IDS recommendations and on compliance rates, and deserve further investigation. We also discuss possible drawbacks of IDSs in acute-care hospitals that are rarely reported in the published literature. Overall, IDSs are valuable to antimicrobial stewardship programmes in hospitals, but their impact depends on many human and organizational factors.

How can we improve antibiotic prescribing in primary care

ABSTRACT Antibiotic stewardship is a necessity given the worldwide antimicrobial resistance crisis. Outpatient antibiotic use represents around 90% of total antibiotic use, with more than half of these prescriptions being either unnecessary or inappropriate. Efforts to improve antibiotic prescribing need to incorporate two complementary strategies: changing healthcare professionals’ behaviour, and modifying the healthcare system. In this review, we present a broad perspective on antibiotic stewardship in primary care in high and high-middle income country settings, focussing on studies published in the last five years. We present the limitations of available literature, discuss perspectives, and provide suggestions for where future work should be concentrated.

Antibiotic resistance: a geopolitical issue

Antimicrobial resistance (AMR), associated with a lack of new antibiotics, is a major threat. Some countries have been able to contain resistance, but in most countries the numbers of antibiotic-resistant bacteria continue to increase, along with antibiotic consumption by humans and animals. AMR is a global issue, and concerns all decision-makers worldwide. Some initiatives have been undertaken in the last 15 years, in particular by the WHO, the European Centre for Disease Prevention and Control, and the CDC, but those initiatives were partial and poorly implemented, without coordination. Very recently, some important initiatives have been implemented by the WHO. Since 2009, a US and European joint task force, the Trans-Atlantic Task Force on Antibiotic Resistance, has been working on common recommendations. At a national level, some important initiatives have been implemented, in particular in European countries and in the USA. The Chennai declaration, in India, is also a good example of a multidisciplinary and national initiative that was highly political. Finally, several non-governmental non-profit organizations are also very active, and have helped to raise awareness about the problem of AMR. In the future, this global issue will need political involvement and strong cooperation between countries and between international agencies.

Human resources estimates and funding for antibiotic stewardship teams are urgently needed

1) Lorraine University, EA 4360 APEMAC, Nancy, France 2) Nancy University Hospital, Infectious Diseases Department, Nancy, France 3) ESCMID Study Group for Antimicrobial stewardshiP (ESGAP) 4) University of Geneva Medical School, Geneva, Switzerland 5) London School of Economics, London, United Kingdom 6) Infectious Diseases, Internal Medicine 1, DZIF Centre, Tübingen University, Germany 7) European Committee on Infection Control (EUCIC) 8) University Medical Centre Ljubljana, Slovenia 9) Faculty of Medicine, University of Ljubljana, Slovenia 10) University Hospital Carl Gustav Carus at the TU Dresden, Division of Infectious Diseases, Dresden, Germany 11) Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium 12) Infection Control Program and Division of Infectious Diseases, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland 13) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Imperial College London, London, UK 14) Leeds Teaching Hospitals NHS Trust, Leeds, UK 15) Division of Infectious Diseases, Department of Medicine, Sinai Health System, University Health Network, University of Toronto, Toronto, Canada 16) Ninewells Hospital and Medical School, Dundee, UK 17) British Society for Antimicrobial Chemotherapy (BSAC), Birmingham, UK 18) Paediatric Infectious Diseases Research Group, St Georges, University of London, London, UK 19) IQ Healthcare, Radboud University Medical Centre, Nijmegen, The Netherlands 20) National Centre for Antimicrobial Stewardship, Royal Melbourne Hospital at the Peter Doherty Institute, Melbourne, Australia 21) Centre for Disease Dynamics, Economics & Policy, New Delhi, India 22) Division of Infectious Diseases & HIV Medicine, Department of Medicine, Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa

Managing responsible antimicrobial use: perspectives across the healthcare system

BACKGROUND Healthcare systems consist of building blocks. Shaping how these building blocks function and interact can promote responsible antimicrobial use, and this represents an important opportunity for managers at different points within healthcare systems to act upon. AIMS To review real-world examples of how healthcare systems can promote responsible antimicrobial use, focusing on the role of governance and managers. SOURCES We searched and reviewed existing literature and official documents, which mostly focused on antibiotics. We also drew on the diverse experiences of the ESGAP (the ESCMID (European Society of Clinical Microbiology and Infectious Diseases) Study Group for Antimicrobial stewardshiP) network. CONTENT First, we explored at the institution level the implementation of antimicrobial stewardship programmes, the need to embrace multidisciplinary approaches, the benefits of engaging with social sciences experts, and the role of governance and leadership. We look beyond individual institutions and highlight the urgent need for workforce capacity estimates for antimicrobial stewardship activities, how antimicrobial stewardship efforts can connect to form networks, and the importance of governance and regulation at national and international levels. IMPLICATIONS Managers in the healthcare system are in a strong position to look beyond individual prescriptions and to recognize the many ways in which different healthcare system building blocks can contribute to responsible use of antimicrobials. At the institution level this can be achieved by implementing antimicrobial stewardship programmes, ensuring they are adequately resourced, and driving buy-in across clinical leadership. At regional and national levels this includes facilitating the sharing of experiences and resources between institutions, and developing the standards and regulations needed to support responsible antimicrobial use.

WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics.

SummaryResistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the five next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practicionners, and veterinarians.

Using antibiotics responsibly: are we there yet?

Problems of antibiotic access and excess coexist in the world today and are compounded by rising rates of antibiotic resistance. We introduce two dimensions of responsibility to this context: responsible individual practices and a broad societal obligation centered on sustainability. Acting on these responsibilities requires recognizing the potential tensions between an individual optimum for antibiotic use and the societal optimum. We relate the tragedy of the commons metaphor to this situation to illustrate the complexity involved, and we draw on real-world experiences in Uganda, India, China and France. We conclude that we must form a global stewardship of antibiotics that can link access, innovation and conservation efforts across countries to ensure sustainable access to effective antibiotics for all who need them.

Antimicrobial stewardship: an international emergency

C. Pulcini and J.-L. Mainardi 1) CHU de Nancy, Service de Maladies Infectieuses, 2) Universit e de Lorraine, EA 4360 APEMAC, Nancy, 3) INSERM, U1138, LRMA, Equipe 12 du Centre de Recherche des Cordeliers, 4) Universit e Pierre et Marie Curie, UMR S 1138, 5) Universit e Paris Descartes, Sorbonne Paris Cit e, UMR S 1138 and 6) Assistance Publique-Hopitaux de Paris, Service de Microbiologie, Hopital Europ een Georges Pompidou, Paris, France E-mail: c.pulcini@chu-nancy.fr

Developing core elements and checklist items for global hospital antimicrobial stewardship programmes: a consensus approach

OBJECTIVES With increasing global interest in hospital antimicrobial stewardship (AMS) programmes, there is a strong demand for core elements of AMS to be clearly defined on the basis of principles of effectiveness and affordability. To date, efforts to identify such core elements have been limited to Europe, Australia, and North America. The aim of this study was to develop a set of core elements and their related checklist items for AMS programmes that should be present in all hospitals worldwide, regardless of resource availability. METHODS A literature review was performed by searching Medline and relevant websites to retrieve a list of core elements and items that could have global relevance. These core elements and items were evaluated by an international group of AMS experts using a structured modified Delphi consensus procedure, using two-phased online in-depth questionnaires. RESULTS The literature review identified seven core elements and their related 29 checklist items from 48 references. Fifteen experts from 13 countries in six continents participated in the consensus procedure. Ultimately, all seven core elements were retained, as well as 28 of the initial checklist items plus one that was newly suggested, all with ≥80% agreement; 20 elements and items were rephrased. CONCLUSIONS This consensus on core elements for hospital AMS programmes is relevant to both high- and low-to-middle-income countries and could facilitate the development of national AMS stewardship guidelines and adoption by healthcare settings worldwide.