Save Antibiotics: a call for action of the World Alliance Against Antibiotic Resistance (WAAAR)

International audienceResistance to antibiotics has recently increased dramatically worldwide. The pipeline of new classes of antibiotics is dry for at least the next few years. Therefore antibiotic resistance represents one of the most problematic public health issues of our time. Treatment failures already happen in increasing numbers for common community-acquired infections, such as urinary tract infections or intra-abdominal infections. This is due in particular to Enterobacteriaceae harboring extended-spectrum beta-lactamases (ESBL). Enterobacteriaceae harboring carbapenemases are also highly prevalent in many countries. In the future, difficult surgical procedures, transplants, and other immunosuppressive therapies may become very risky. Resistance is mainly due to an excessive usage of antibiotics, in both humans and animals, and to cross-transmission of resistant bacteria. Action is urgently needed. Therefore, a World Alliance Against Antibiotic Resistance (WAAAR) was created in 2011. It includes healthcare professionals, consumers, health managers, and politicians. We present here the main measures proposed by the Alliance, as a result of a strong consensus between the different stakeholders, including general practitioners and veterinarians

Forgotten Antibiotics: An Inventory in Europe, the United States, Canada, and Australia

In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious disease specialists in Europe, the United States, Canada, and Australia. An international expert panel selected systemic antibacterial drugs for their potential to treat infections caused by resistant bacteria or their unique value for specific criteria. Twenty-two of the 33 selected antibiotics were available in fewer than 20 of 38 countries. Economic motives were the major cause for discontinuation of marketing of these antibiotics. Fourteen of 33 antibiotics are potentially active against either resistant Gram-positive or Gram-negative bacteria. Urgent measures are then needed to ensure better availability of these antibiotics on a global scal

How are trainees in clinical microbiology and infectious diseases supervised in Europe? An international cross-sectional questionnaire survey by the Trainee Association of ESCMID

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Essential and Forgotten antibiotics:an inventory in low- and middle-income countries

Background: The World Health Organization Essential Medicines List (WHO-EML) includes ‘access’ antibiotics, judged essential to treat common infections. The European Society of Clinical Microbiology and Infectious Diseases Study Group for Antimicrobial Stewardship defined a list of ‘forgotten’ antibiotics, some old and often off-patent antibiotics, which have particular value for specific indications. Objective: To investigate which WHO-EML ‘access’ and ‘forgotten’ antibiotics are approved at national level in a sample of low- to middle-income countries (LMICs). Methods: The Scientific Committee used a consensus procedure to select 26 WHO-EML ‘access’ and 15 ‘forgotten’ antibiotics. Paediatric formulations were explored for 14 antibiotics. An internet-based questionnaire was circulated to 40 LMIC representatives. Antibiotics were defined as approved if an official drug regulatory agency and/or the national ministry of health licensed their use, making them, at least theoretically, available on the market. Results: Twenty-eight LMICs (11 in Africa, 11 in Asia and six in America) were surveyed. Nine WHO-EML ‘access’ antibiotics (amoxicillin, ampicillin, benzylpenicillin, ceftriaxone, clarithromycin, ciprofloxacin, doxycycline, gentamicin and metronidazole) were approved in all countries, and all 26 ‘access’ antibiotics were approved in more than two-thirds of countries. Among the 15 ‘forgotten’ antibiotics, only one was approved in more than two-thirds of countries. The median number of approved antibiotics per country was 30 (interquartile range 23–35). Six of 14 paediatric formulations (amoxicillin, amoxicillin-clavulanic acid, oral antistaphylococcal penicillin, cotrimoxazole, erythromycin and metronidazole) were approved in more than two-thirds of countries. Conclusions: WHO-EML ‘access’ antibiotics and the most frequently used formulations for paediatrics were approved in the vast majority of the 28 surveyed LMICs. This was not the case for many of the ‘forgotten’ antibiotics, despite their important role, particularly in areas with high prevalence of multi-drug-resistant bacteria

Forgotten antibiotics : a follow-up inventory study in Europe, the USA, Canada and Australia

The objective of this study was to update a 2011 survey, conducted on behalf of the ESCMID Study Group for Antibiotic Policies (ESGAP), studying the availability of old but clinically useful antibiotics in North America, Europe and Australia. This follow-up survey was performed in 2015 in 40 countries among specialists from the pharmaceutical, infectious diseases and microbiology sectors in North America, Europe and Australia in order to assess the availability through usual marketing processes of 36 systemic antibiotics (addition of 3 antibiotics compared with the 2011 survey) selected for their ability to treat infections caused by resistant bacteria and their unique value for specific criteria. The questionnaire was sent by e-mail to national contacts belonging to ESGAP and ReAct networks. In all, 39 of the 40 countries participated in this survey. The number of available antibiotics differed considerably from one drug to another as well as from one country to another (e.g. 7 antibiotics available in Estonia, 24 in France). Overall, 25/36 selected antibiotics were marketed in 20/39 countries or less. From 2011 to 2015 (data available for both periods in 37 countries for 33 antibiotics), the number of available selected antibiotics increased in 13 countries and decreased in 17. In conclusion, despite the ongoing bacterial resistance crisis, the situation regarding the availability of ‘forgotten antibiotics’ has worsened since 2011. Urgent measures are needed to ensure better availability of these antibiotics on a global scale as a conservation measure to ensure sustainable and responsible use of antibiotics.peer-reviewe

Legal framework of antimicrobial stewardship in hospitals (LEASH) : a European Society of Clinical Microbiology and Infectious Diseases (ESCMID) cross-sectional international survey

Antimicrobial stewardship (AMS) is the cornerstone activity in the combat against antimicrobial resistance. In order to ensure sustainable deployment and development of AMS, a strategic and regulatory framework needs to be provided by national healthcare authorities. Experts from 32 European countries, Israel and Turkey were invited to participate in a cross-sectional internet-based survey from October 2016 to May 2017 on the legal framework and mandatory components (structures, activities) of AMS in hospitals, i.e. components required by legislation or regulations. We collected data from 25 countries and two regions (in countries with federal health administration). Laws regulating AMS existed in seven countries and one region. Other health ministry regulations were applicable in 13 countries and one region. National strategies and/or action plans approved by ministries of health were in place in 13 countries and one region. Conversely, five countries and one region had no regulation of AMS in hospitals. Funding for AMS in hospitals was provided in five countries and one region. Eight countries and one region reported mandatory AMS structures and activities complying with the Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) structure, policy and practice indicators. In 10/27 cases, however, the mandatory AMS activities were not being fully carried out. The survey showed heterogeneous legal frameworks for AMS in hospitals, and in many countries it was even lacking. The situation may be critical in countries with poor control of antimicrobial use and resistance. Recent international initiatives calling on policy-makers to address the threat of antimicrobial resistance could yield improvement.peer-reviewe

Variation in antibiotic use among and within different settings: a systematic review

Objectives: Variation in antibiotic use may reflect inappropriate use. We aimed to systematically describe the variation in measures for antibiotic use among settings or providers. This study was conducted as part of the innovative medicines initiative (IMI)-funded international project DRIVE-AB. Methods: We searched for studies published in MEDLINE from January 2004 to January 2015 reporting variation in measures for systemic antibiotic use (e.g. DDDs) in inpatient and outpatient settings. The ratio between a study's reported maximumand minimumvalues of a given measure [maximum: minimumratio (MMR)] was calculated as a measure of variation. Similar measures were grouped into categories and when possible the overall median ratio and IQR were calculated. Results: One hundred and forty-three studies were included, of which 85 (59.4%) were conducted in Europe and 12 (8.4%) in low-to middle-income countries. Most studies described the variation in the quantity of antibiotic use in the inpatient setting (81/143, 56.6%), especially among hospitals (41/81, 50.6%). Themost frequentmeasure was DDDs with different denominators, reported in 23/81 (28.4%) inpatient studies and in 28/62 (45.2%) outpatient studies. For this measure, we found a median MMR of 3.7 (IQR 2.6-5.0) in 4 studies reporting antibiotic use in ICUs in DDDs/1000 patient-days and a median MMR of 2.3 (IQR 1.5-3.2) in 18 studies reporting outpatient antibiotic use in DDDs/1000 inhabitant-days. Substantial variationwas also identified in othermeasures. Conclusions: Our review confirms the large variation in antibiotic use even across similar settings and providers. Data from low-and middle-income countries are under-represented. Further studies should try to better elucidate reasons for the observed variation to facilitate interventions that reduce unwarranted practice variation. In addition, the heterogeneity of reported measures clearly shows that there is need for standardization

Amoxicillin dosing recommendations are very different in European countries : a cross-sectional survey

National antibiotic stewardship programmes recommend monitoring antibiotic consumption and benchmarking. The WHO recommend the Anatomic Therapeutic Chemical classification and respective Defined Daily Doses (DDD) for drug utilization research. This is the most frequently used unit of measure within the European Union (EU). Wide variations in antibiotic consumption exist between EU countries in the outpatient setting, ranging in 2012 from 11.3 (the Netherlands) to 31.9 DDD per 1000 inhabitants and per day (Greece). Penicillins are the most consumed antibacterial agents in the community in all EU countries. Amoxicillin and amoxicillin/clavulanate are the two most widely prescribed penicillins, except in Denmark, Norway and Sweden where penicillin V and other very narrow-spectrum penicillins are used preferentially.peer-reviewe

Antibiotic research and development: business as usual?

This article contends that poor economic incentives are an important reason for the lack of new drugs and explains how the DRIVE-AB intends to change the landscape by harnessing the expertise, motivation and diversity of its partner