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NEWSLETTER Volume 38, No NEWSLETTER Volume 38, No. 3: Autumn 2020 Page No. Feature Articles 3. Emerging threats of antibiotics in the environment: what about the pharmaceutical industry? Véronique Mondain, Florence Lieutier-Colas 6. A Multidisciplinary, French-speaking course on Antimicrobial Stewardship in Africa: the MUFASA Project Armel Poda, Abdoul-Salam Ouédraogo, Sylvain Godreuil, Jean- Baptiste Guiard-Schmid, Xavier Lescure, Pierre Tattevin 8. Bacteriophages: when history can save the future Fatima Allaw, Jean-Francois Jabbour, Souha S. Kanj APUA / ISAC and Antimicrobial Resistance News 10. Antimicrobial Resistance in the News 12. APUA News 13. ISAC News 15. About ISAC / APUA www.APUA.org www.ISAC.world 1 “Preserving the Power of Antibiotics” APUA Board Members International Advisory Board Lilian Abbo (USA) Revathi Gunturu (India) Paul Pottinger (USA) Jacques Acar (France) David Heymann (UK) Jose Ramiro (USA) Carlose Amabile Cuevas (Mexico) Nadia H. Ismail (Saudi Arabia) Susan Seo (USA) Fernando Baquero-Mochales (Spain) Pota Kalima (UK) Wing-Hong Seto (Hong Kong) Michael Bennish (South Africa) Sam Kariuki (Kenya) Atef Shibl (Saudi Arabia) Jean Carlet (France) Calvin Kunin (USA) Stefania Stefani (Italy) Sujith J Chandy (India) Stephen Lerner (USA) Karin Thursky (Australia) Patrice Courvalin (France) Jay Levy (USA) Jos van der Meer (the Netherlands) George Daikos (Greece) Victor Lim (Malaysia) Anne Vidaver (USA) Ziad Daoud (Lebanon) Fernando Luis Lopes Cardozo (Brazil) Vera Vlahovic-Palcevski (Croatia) Anahi Dresser (Mexico) David Lye (Singapore) Erica Vlieghe (Belgium) Sherwood Gorbach (USA) Linus Ndegwa (Kenya) Ibrahim Yusuf (Nigeria) Tom Gottlieb (Australia) Mihai Nechifor (Romania) Newsletter Editorial Team: Fiona MacKenzie (Managing Editor) and Fee Johnstone (Editorial Assistant) Disclaimer APUA / ISAC accept no legal responsibility for the content of any submitted articles, nor for the violation of any copyright laws by any person contributing to this newsletter. The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recom- mended by APUA ISAC in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary prod- ucts are distinguished by initial capital letters. The APUA Newsletter (ISSN 1524-1424) © 2020 APUA Since 1983, the APUA Newsletter has been a continuous source of non-commercial information disseminated without charge to healthcare practitioners, researchers, and policy-makers worldwide. The Newsletter carries up-to-date scientific and clinical information on prudent antibiotic use, antibiotic access and effectiveness, and management of antibiotic resistance. The publication is distributed to over 7,000 affiliated individuals in more than 100 countries. The material provided by APUA is designed for educational purposes only and should not be used or taken as medical advice. We encourage distribution with appropriate attribution to APUA. See previous editions of the Newsletter on the APUA website. *APUA welcomes contributions and Letters to the Editors. Please send us your thoughts and questions. Names will be published but not addresses. All content may be edited for style and length. Please email [email protected] 2 • APUA / ISAC Newsletter Vol 38. No 3 • © APUA / ISAC 2020 Emerging threats of antibiotics in the environment: what about the pharmaceutical industry? Véronique Mondain, Florence Lieutier-Colas Véronique Mondain Florence Lieutier-Colas Infectious Diseases Department, AntibioEst Infectiology Regional Network, University Hospital of Nice, France University Hospital of Nancy, France “Antibiotic resistance is no longer a prediction for the widely used in the EU and in the 2016 United Nations future.” Political Declaration on AMR3. The World Health Organization (WHO) 2014 report on Global Surveillance of Antimicrobial Resistance (AMR) The natural environment presents a transmission revealed that: “It is happening right now, across the route and a reservoir for resistant microorganisms. It is world, and it is putting at risk the ability to treat well known that such bacteria and antibiotic resistance common infections in the community and hospitals"1. genes (ARG) are ubiquitous in nature: they can indeed WHO and other eminent global health experts warn be found in high concentrations in clinical, industrial that we are at the dawn of a “post-antibiotic era”. The and urban wastewater, as well as in animal husbandry. UK Independent Review on AMR projects a worldwide Moreover, the environments frequently contain very death toll of 10 million people per annum by 2050, if high levels of antibiotics and pharmaceuticals4,5,6,7. resistance is left unchecked, with a cost of up to $100 One of the very first to take an interest, Larsson et al trillion. analysed pharmaceuticals in the effluent from a wastewater treatment plant Several interconnected human, “Information about the serving approximately 90 bulk drug animal and environmental habitats manufacturers in Patancheru, near can contribute to the emergence, origin of Active Hyderabad, India which is a major evolution and spread of AMR. Pharmaceutical Ingredients production site of generic drugs for Better managing this problem the world market8. The samples includes taking steps to preserve and the finished products contained by far the highest levels the continued effectiveness of of pharmaceuticals reported in any existing antimicrobials such as that end up on our effluent. The high levels of several trying to eliminate their pharmacy shelves is kept broad-spectrum antibiotics raise inappropriate use in both human concerns about resistance and veterinary medicine. Despite confidential by drug firms.” development. The concentration of publication of WHO guidelines the most abundant drug, recommending the discontinuation of the prescription ciprofloxacin (up to 31,000 μg/l), exceeds levels toxic of antibiotics as growth factors, many countries do not to some bacteria by over 1000-fold. In 2017, Lübbert comply and even plan to increase the use of those et al sampled different sites and wastewaters in an antibiotics in intensive industrial farming2. Pollution urban Indian territory where a major production area from inadequate treatment of industrial, residential is also settled for the global bulk drug market: they and farm waste increases the spread of resistant found that all environmental sampling sites were bacteria in the environment. Numerous countries and contaminated with very high concentrations of several international agencies have now included a antimicrobials, in particular moxifloxacin, voriconazole “One Health Approach” within their action plans to and fluconazole; and that microbiological analyses fight AMR. “One Health” is defined as a concept and revealed an extensive presence of Extended Spectrum approach to “designing and implementing Beta Lactamase (ESBL), Carbapenemase Producing programmes, policies, legislation and research, in Enterobacteriaceae (CPE) and non-fermenters in more which multiple sectors communicate and work than 95% of the samples7. The relative abundance of together to achieve better public health outcomes”. total ARG was 30-fold higher in river sediments within This term is now globally recognised, having been the city, compared to upstream sites. Mondain et al • APUA / ISAC Newsletter Vol 38. No 3 • © APUA / ISAC 3 Despite those studies, few actions have been taken to have an ethical vocation to be at the origin of the improve the situation. It was not until 2011 that a worldwide dissemination of AMR. The COVID-19 crisis, European action plan against AMR mentioned the which also results in drug shortages, could be a trigger problem of pollution from production sites. In 2013, a for this movement towards greater security of directive required member states to develop a medicine supply. strategic approach against water pollution by pharmaceutical substances within two years. One of However, these concerns no longer apply only to low- the measures envisaged plans to include to middle– income countries (LMICs) where hygiene environmental criteria in the guides to "Good and sanitation may be lower. Czekalski et al showed Manufacturing Practice". However, the opacity is such increased levels of multi drug resistant (MDR) bacteria that to date it is almost impossible to obtain and ARGs after wastewater treatment and manufacturing traceability and therefore it is actually dissemination into Lake Geneva, in Switzerland4. difficult for a pharmaceutical firms to follow Finally, it must be remembered that healthcare compliance with environmental standards. settings themselves may act as a potential reservoir for Information about the origin of Active Pharmaceutical environmental pollution with MDR or even hospital- Ingredients (APIs) and the finished products that end acquired outbreaks with MDR pathogens10, 11, 12. up on our pharmacy shelves is kept confidential by drug firms, which are unwilling to open up their To conclude, we have to act on different scales in supplier relationships to public scrutiny. Regulators, human medicine, in farms and in our environment, by who could easily demand greater transparency from limiting antibiotic consumptions and effluents, and the pharmaceutical industry, have so far shied away improving surveillance and research in these areas. In from taking action9 . 2018, WHO issued a public document whose target is to improve awareness and to educate any kind of Practical proposals could be made:
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