New DEEP-URO study builds on GPIU success It’s time to find a solution for antimicrobial-resistant bacteria
international offices, and pharmaceutical companies. Our goal was to design and develop a dynamic Pan-European scientific platform, capable of connecting and operating many independent, integrative modules. We aimed to create a global network for infectious disease research and patient care, with UTI serving as the pilot specialty of the platform (Figure 3a, 3b, and 4). After careful consideration, we realised that we were at a crossroads. The success of our SENTRII project had put us in a favourable position to secure funding for several years. However, we were faced with a crucial decision: should we continue with a more educational and developmental project, or shift our focus to a more urology-centric research project that would address the pressing challenges of antibiotic resistance? After much discussion, we decided to pursue a new concept called DEEP-URO (DE- Escalation of antibiotic Prophylaxis in UROlogical procedures for prevention/tackling of antibiotic resistance). By leveraging our experience with GPIU, the shortcomings we had encountered, and the new ideas we had developed for SENTRII, we believed that we could make a meaningful contribution to the field of urology and tackle one of the most pressing public health challenges of our time. In 2021, a dedicated research group was formed with a vision to provide evidence-based answers to all relevant knowledge gaps in the field of genitourinary tract infections that have real-life impact on patients. The group adopted a very focused, management oriented working structure to effectively identify, design, organise and implement multiple research projects. We realised that antibiotic prophylaxis was a field where lack of evidence hinders our ability to provide the best practice to our patients in urology. DEEP-URO study In the world of medicine, overuse of antibiotics in surgical prophylaxis is a serious issue that contributes to the growing problem of antimicrobial resistance. This can lead to difficulty in treating even the most basic infections after surgery. That's why the DEEP-URO study is so important. It aims to increase our understanding of rates and risk factors for infectious complications in urology and to determine the actual need for antibiotic prophylaxis in urological procedures. The traditional study designs used in medicine may not be the most efficient way to generate the necessary evidence due to the many technical variations in surgical procedures, patient factors, available antibiotics, and spatiotemporal variation of antimicrobial resistance. That's why the DEEP-URO study has a novel design to generate high-level evidence for appropriate use of antibiotic prophylaxis in urology. By evaluating the effectiveness and necessity of antibiotic prophylaxis de-escalation for select urological interventions, the DEEP-URO study offers a new approach to solving this critical problem. The study design is summarised in Figure 5.
Prof. Truls Erik Bjerklund Johansen
Dept. of Urology Oslo University Hospital (NO)
tebj@medisin.uio.no
Co-authors: Dr. Zafer Tandoğdu (GB), Prof. Tommaso Cai (IT), Prof. Florian Wagenlehner (DE), Dr. Béla Köves (HU), Prof. Kurt Naber (DE) Over the past 20 years we have been conducting the Global Prevalence Study of Infections in Urology (GPIU), which has allowed us to identify the increasing threat of antimicrobial-resistant (AMR) bacteria. This has been a collective effort with the support of the urology community. We are proud to have established a unique position to demonstrate the problem of AMR in urology, and we have been successful in raising awareness of the issue through our research and publications. However, we know that this is not enough. With the increasing threat of AMR, we need to take action to find a solution. That's why we are embarking on a new journey with the DEEP-URO study, where we aim to evaluate the effectiveness of de-escalation of antibiotic prophylaxis in reducing the incidence of infectious complications and antibiotic resistance while maintaining patient safety. We are confident that with our established collective altruistic approach, we can contribute to tackling AMR in urology, and our efforts will contribute worldwide (Figure 1). “We are confident that with our established collective altruistic approach, we can contribute to tackling AMR in urology, and our efforts will contribute worldwide.” The PEP, PEAP and GPIU studies It all began with Dr. Paul Madsen (DK), who journeyed to Wisconsin with his German spouse in pursuit of their American aspirations. As a result of his contributions to medicine, he was bestowed an honorary degree by the Danish Queen. Dr. Madsen initiated a program of one-year fellowships in urology for talented and driven young urologists. Among the Danes in this group was a German man named Prof. Naber, who was introduced to the study of urinary tract infections. At the EAU congress in Paris in 1996, Prof. Kurt Naber assembled a group of experts from around the world to discuss the pressing issues surrounding UTIs and antibiotic treatment in urology. Invitees included luminaries like Dr. Joan Palou Redorta (ES), Prof. Bernard Lobel (FR), Prof. Henry Botto (FR), Prof. Michael Bishop (UK), Prof. Péter Tenke (HU), Prof. Hakki Mete Cek (TR), and Prof. Bjerklund Johansen. At that time, many of us were unfamiliar with terms such as pharmacokinetics, pharmacodynamics and nosocomial. In 2000, we founded the European Society for Infections in Urology and produced the inaugural edition of the EAU guidelines on UTI. The society later became a full section of the EAU. Background It was clear to us that infective complications could pose a significant threat to the success of surgeries. One of the most prevalent diseases we encountered was urinary tract infection (UTI). It became evident that reducing infective complications could serve as a vital tool in improving the quality of care we provided. However, the rate of infective complications in urology, the causative agents, and risk factors were not well understood. We proposed establishing a prevalence registry through an electronic network like the recently established virtual Institute of Urology in Norway. Prof. Bishop voiced his scepticism, stating that this was not possible on an international level.
Fig. 1: New leaders: Prof. Wagenlehner and Dr. Köves are replaced by Dr. Tandoğdu and Prof. Tommaso Cai as chair and co-chair of ESIU
Fig. 2: Development meeting of DEEP-URO study. From left: Dr. Bela Köves, Dr. Tandoğdu, Prof. Bjerklund Johansen, Prof. Naber and Prof. Wagenlehner in Giessen, Germany
Nonetheless, we persevered, and the first annual registration was conducted in 2003. It was christened the Pan European Prevalence study (PEP-study). The registration process proved to be a resounding success, and the study was repeated the following year as the Pan Euro-Asian Prevalence study (PEAP-study). The success of the study continued, and it evolved into GPIU, the G lobal P revalence study on I nfections in U rology. By 2015, the study was operational in 73 countries, and over the years, more than 30,000 hospitalised urological patients have been screened for hospital-acquired infections. [1] Funding and technology From the beginning, the ESIU and its UTI guidelines panel have faced challenges in finding sponsors due to our unique stance of trying to reduce overconsumption of antibiotics. Nevertheless, we have had the full support of the EAU, EAU Research Foundation, and its secretary generals. Urologists drafted the CRFs and IT structure, and IT engineers at the EAU developed the applications. The study platform relocated to the Technische Hochschule in Mittelhessen (THM) in Giessen, Germany, with more IT support available as the study expanded. Annual grants from the Swiss Merian Iselin Clinic and the invaluable contributions of Prof. Gernot Bonkat (CH) facilitated this relocation. Outcomes The PEP and PEAP studies provided crucial insights into hospital acquired infections in urology, including microorganisms causing these infections and their resistance rates to commonly used antibiotics. Over the years, the annual studies have yielded an abundance of data, which has been instrumental in enhancing our understanding of UTI. With these data, we have developed a new clinical classification of UTI, defined contamination categories, identified risk factors, established antibiotic stewardship measures, and informed guidelines on treatment and prophylaxis. Furthermore, several side studies have been performed, including infective complications after prostate biopsies [2] and the SERPENS study on urosepsis which provided valuable data from nearly 1000 patients. The GPIU project has produced numerous lectures, abstracts, articles and doctoral theses, culminating in the ICUD book and the Living textbook, both serving as living monuments of our efforts [3,4]. Most recently, GPIU data was utilised to develop an optimal empirical treatment model for UTI through Bayesian mathematics [5]. The transition As medical journals and guideline developers came to pay increasing attention to study design and level of evidence, it became more difficult to get our
retrospective data analyses published and to influence guidelines recommendations. We were criticised for a continuous retrospective approach and for random inclusion of study centres over the years. Not even the best mathematical modelling could compensate for that. We could also not provide evidence that local investigators had been trained to fill in report forms. Although the study always had a central ethical approval, hospitals in some countries questioned the need for approval by local and regional ethical committees. Meanwhile, nosocomial infections and antimicrobial resistance was increasing and there were few, if any new antibiotics in the pipelines of pharmaceutical companies. The trends we had been studying, the needs we had identified and the measures we had called for were named by others as “antimicrobial stewardship” [6]. A comprehensive evaluation performed on assignment by the UK government told us that our topic was at the heart of an imminent crisis (The O`Neil report). We realised that our experience was valuable but also that we needed to re-define our goals and our way of working. Several meetings were held in the core study group (Figure 2). With great enthusiasm and determination, we embarked on a months-long journey to develop an application for the EU cost project, SENTRII. This project was nothing short of ambitious, with the support of numerous esteemed researchers, research institutions, scientific organisations,
DEEP-URO will use an innovative study platform that has the potential to improve the use of antibiotics
EAU Section of Infections in Urology (ESIU)
Fig. 3a and b: Dr. Tandoğdu and Dr. Köves discussing the transition from GPIU to DEEP-URO
European Urology Today
26
April/May 2023
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