[{"command":"openDialog","selector":"#drupal-modal","settings":null,"data":"\u003Cdiv id=\u0022republish_modal_form\u0022\u003E\u003Cform class=\u0022modal-form-example-modal-form ecl-form\u0022 data-drupal-selector=\u0022modal-form-example-modal-form\u0022 action=\u0022\/en\/article\/modal\/12825\u0022 method=\u0022post\u0022 id=\u0022modal-form-example-modal-form\u0022 accept-charset=\u0022UTF-8\u0022\u003E\u003Cp\u003EHorizon articles can be republished for free under the Creative Commons Attribution 4.0 International (CC BY 4.0) licence.\u003C\/p\u003E\n \u003Cp\u003EYou must give appropriate credit. We ask you to do this by:\u003Cbr \/\u003E\n 1) Using the original journalist\u0027s byline\u003Cbr \/\u003E\n 2) Linking back to our original story\u003Cbr \/\u003E\n 3) Using the following text in the footer: This article was originally published in \u003Ca href=\u0027#\u0027\u003EHorizon, the EU Research and Innovation magazine\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003ESee our full republication guidelines \u003Ca href=\u0027\/horizon-magazine\/republish-our-stories\u0027\u003Ehere\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003EHTML for this article, including the attribution and page view counter, is below:\u003C\/p\u003E\u003Cdiv class=\u0022js-form-item form-item js-form-type-textarea form-item-body-content js-form-item-body-content ecl-form-group ecl-form-group--text-area form-no-label ecl-u-mv-m\u0022\u003E\n \n\u003Cdiv\u003E\n \u003Ctextarea data-drupal-selector=\u0022edit-body-content\u0022 aria-describedby=\u0022edit-body-content--description\u0022 id=\u0022edit-body-content\u0022 name=\u0022body_content\u0022 rows=\u00225\u0022 cols=\u002260\u0022 class=\u0022form-textarea ecl-text-area\u0022\u003E\u003Ch2\u003EEU research alliance fights back against resistant super-bacteria\u003C\/h2\u003E\u003Cp\u003EBacterial infections are a major health challenge, killing around 100 Europeans a day as they become increasingly resistant to common antibiotics. To address this, researchers like Dr Rienk Pypstra are working together to create more effective treatments.\u003C\/p\u003E\u003Cp\u003EThe problem with bacteria \u2013 one of the simplest life forms \u2013 is that they evolve very quickly.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u201cWith diabetes or heart diseases, for example, the human body is not evolving at a speed that means we have to have new treatments every three or four years,\u201d said Pypstra, an expert in drug development and head of Infectious Diseases at UK specialist pharmaceutical consultancy tranScrip.\u003C\/p\u003E\u003Cp\u003EBut it is different with infections, he warned, because \u201cpathogens have such a short duplication time and are present in such big quantities that you see natural evolution at a very high speed\u201d.\u003C\/p\u003E\u003Cp\u003EPypstra coordinated the eight-year EU-industry co-funded COMBACTE-CARE research project, which ended in 2023. Working with an academic consortium, hospitals and laboratories across the EU, it laid the groundwork for research into antimicrobial resistance and development of better treatments.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EGiven the fickle nature of pathogens, the task was far from simple.\u003C\/p\u003E\u003Cp\u003E\u201cWhenever we develop a new antibiotic, after a couple of years, pathogens emerge that have found a way to escape, and they start to proliferate, and they take over.\u201d\u003C\/p\u003E\u003Cp\u003EAntimicrobial resistance is now considered one of the greatest global public health challenges. In laboratory conditions, some bacteria can double every 20 minutes and start developing resistance to antibiotics in about 10 days.\u003C\/p\u003E\u003Cp\u003EIn the European Economic Area (EU countries plus Iceland, Liechtenstein and Norway), antimicrobial resistance is estimated to be responsible for 35 000 deaths every year, according to data by the European Centre for Disease Prevention and Control. Without a concerted effort to address resistance, there are fears this could rise to around 390 000 by 2050.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ENew treatments\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EThe public-private research project that Pypstra coordinated was part of efforts to produce new treatments for multidrug-resistant bacterial infections.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThe aim was to find treatments for ailments, including complicated urinary tract infections, abdominal infections (often contracted following major surgery), and hospital-acquired lung infections, such as ventilator-associated pneumonia.\u003C\/p\u003E\u003Cp\u003EAll those can be caused by bacteria resistant to a class of antibiotics known as carbapenems.\u003C\/p\u003E\u003Cp\u003E\u201cFor a long time, carbapenems were the \u2018last-resort antibiotics\u2019,\u201d Pypstra said. \u201cThen some bacteria emerged that could break down these carbapenems, and some of those are even resistant to the latest drugs.\u201d\u003C\/p\u003E\u003Cp\u003EWith resistance increasing, the World Health Organization now lists various carbapenem-resistant bacteria as priority pathogens, requiring research and development of new drugs.\u003C\/p\u003E\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003EWhenever we develop a new antibiotic, after a couple of years, pathogens emerge that have found a way to escape.\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EDr Rienk Pypstra, COMBACTE-CARE\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\u003Cp\u003EOne particular problem is a specific subclass of carbapenem-resistant infections caused by bacteria which produce enzymes that accelerate the breakdown of carbapenems and render them ineffective.\u003C\/p\u003E\u003Cp\u003ETo tackle those bacteria, doctors were previously using older toxic agents or combining two specific antibiotics. But while the latter approach has had some success, it was fraught with difficulties.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThe optimal dose of the two antibiotics was unclear, and they were often given to patients as separate intravenous infusions, on different time schedules. This made it less effective and complicated for medical staff.\u003C\/p\u003E\u003Cp\u003EAlong with the usual safety and efficacy trials and non-clinical studies to find the optimal dose of each antibiotic in the combination, researchers also had to overcome some \u201cmanufacturing difficulties\u201d as the two drugs are chemically very different, Pypstra said.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ETheir research led to a novel treatment that was recently granted marketing authorisation in the EU by the European Commission.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EPublic-private partnership\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EThe development of new treatments in this field was supported by the Innovative Medicines Initiative (IMI), a\u0026nbsp;public-private partnership between the EU and the European pharmaceutical industry.\u003C\/p\u003E\u003Cp\u003EPypstra said it was important to show that such a partnership can work because antimicrobial resistance needs \u201cother sources of funding besides the private market\u201d.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EWith antibiotics, investment returns for drug manufacturers are limited and slow, often discouraging antibiotic research and development. Unlike many new drugs, antibiotics are not used as quickly and broadly as possible upon release, for several reasons.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EFirstly, resistance spreads gradually, so initially there is not much need for widespread use of new antibiotics.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ESecondly, antimicrobial stewardship \u2013 a globally accepted approach to reduce misuse of antibiotics \u2013 dictates that new antibiotics are kept in reserve.\u003C\/p\u003E\u003Cp\u003E\u201cYou don\u2019t want to suddenly start using them broadly, because then you will very quickly select new mechanisms of resistance,\u201d Pypstra explained. \u201cYou keep the best drugs on the shelf.\u201d\u003C\/p\u003E\u003Cp\u003EBut public-private partnerships aim to put the overall return on investment for drug companies on a par with other therapeutic areas, he said.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ECollaborative network\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EPypstra said that collaboration between academic centres and industry has proved very successful.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ECollaborations of this kind have since evolved into a clinical trial network called Ecraid (European Clinical Research Alliance on Infectious Diseases), which builds on the work by IMI COMBACTE projects and on other EU research projects.\u003C\/p\u003E\u003Cp\u003EWith 19 organisations across six countries, including from 600 to 700 hospitals across Europe, it offers a single point of access to a pan-European clinical research network for infectious disease.\u003C\/p\u003E\u003Cp\u003EThe network\u2019s aim is to conduct trials for infectious diseases, including antimicrobial resistance, explained Ecraid\u2019s chief executive, Professor Marc Bonten, an infectious disease epidemiologist at UMC Utrecht in the Netherlands.\u003C\/p\u003E\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003EThe clinical evaluation of new antibiotics is extremely challenging because trials are on patients with acute infections that must be treated immediately.\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EProfessor Marc Bonten, ECRAID-Base\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\u003Cp\u003E\u201cThe clinical evaluation of new antibiotics is extremely challenging because trials are on patients with acute infections that must be treated immediately,\u201d Bonten said.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EThis means there is little time for doctors to enrol patients in regular trials for new antibiotics. But a series of so-called perpetual observational studies conducted by the network could help address these time constraints.\u003C\/p\u003E\u003Cp\u003EThese clinical studies, which enrol patients on a perpetual basis, collect data on antimicrobial-resistant bacterial infections in hospitals. They include patient risk factors, type of infection, bacteria involved, treatments used and patient outcomes.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u201cThese observational data will allow epidemiological analysis, but the main goal is to create an infrastructure that will help us to do clinical trials more efficiently,\u201d Bonten said.\u003C\/p\u003E\u003Cp\u003EThe studies are carrying out many of the processes needed for clinical trials, such as enrolling patients and collecting appropriate data.\u003C\/p\u003E\u003Cp\u003EThis means that in the future, trials of new antibiotics and treatment combinations can plug into the network without having to start from scratch. In addition, they will also have background epidemiological data to compare their results against.\u003C\/p\u003E\u003Cp\u003E\u201cThe goal is to deliver and create an infrastructure in which randomised controlled trials can be embedded very efficiently,\u201d Bonten said.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u201cSo, for any new antibiotic in the field of ventilator-associated pneumonia, complicated urinary tract infection or acute respiratory infection, we now have a tested system of hospitals across Europe that can enrol patients for trials.\u201d\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EResearch in this article was funded by the EU\u2019s Framework Programme, including, in the case of COMBACTE-CARE, via the Innovative Medicines Initiative\u0026nbsp;(IMI). The views of the interviewees don\u2019t necessarily reflect those of the European Commission. 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