Global spread - Antibiotic resistance a critical sustainability question 2/14/2018. Managing resistance is in everyones interest

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Antibiotic resistance a critical sustainability question D. G. Joakim Larsson, Professor in Environmental Pharmacology Director, Centre for Antibiotic Resistance Research at University of Gothenburg (CARe) Department of Infectious Diseases, Institute for Biomedicine; The Sahlgrenska Academy at the University of Gothenburg E-mail: Personal website: CARe website: joakim.larsson@fysiologi.gu.se http://www.biomedicine.gu.se/joakimlarsson www.care.gu.se More antibiotic resistance means. Global spread - Managing resistance is in everyones interest increased morbidity and mortality increased health care costs increased societal costs Increased inequality Bengtsson-Palme J, Angelin M, Huss M, Kjellqvist S, Kristiansson E, Palmgren H, Larsson DGJ, Johansson A. (2015) The human gut microbiome as a transporter of antibiotic resistance genes between continents. Antimicrobial Agents and Chemotherapy. doi: 10.1128/AAC.00933-15 Johnning A, Kristiansson E, Martin A, Marathe NP, Shouche YS, Johansson A, Larsson DGJ. (2015) Quinolone resistance mutations in the faecal microbiota of Swedish travellers to India. BMC Microbiology. 15:235. Resistant bacteria travel but local stewardship still matters a lot! ECDC, 2017 1

Antibiotic use is linked to antibiotic resistance No new classes of antibiotics against gram-negative bacteria approved in decades ECDC, EFSA and EMA second joint report, 2017 (data from 2015) New antibiotics Reduce need for new antibiotics Limiting infections (transmission control, vaccines) Reduce resistance development via e.g. appropriate use (surveillance, diagnostics, stewardship) Antibiotic resistance in the environment is ancient Resistance i harmless bacteria Resistance in pathogens vanx bla tetm Could be a rare or one time event anywhere Nature (2011) 477:457-61 2

Where do these critical events occur? Patancheru, India Major production of active pharmaceutical ingredients to the world market Photo: C. de Pedro (2006) Surface, ground and drinking water highly contaminated with antibiotics and other drugs 30 mg/l ciprofloxacin 30 ng/l ciprofloxacin Larsson DGJ, de Pedro C, Paxeus N. 2007. Effluent from drug manufactures contains extremely high levels of pharmaceuticals. J Haz Mat. 148 (3), 751-755 J Fick, H Söderström, RH Lindberg, Chau DNP, M Tysklind, DGJ Larsson 2009. Contamination of surface, ground, and drinking water from pharmaceutical production. Environmental Toxicology & Chemistry 28:2522 2527 3

No other environment carry as many antibiotic resistance genes Bacteria from these environments are very efficient in transferring novel resistance plasmids to E.coli N=864 metagenomes Pal C, Bengtsson-Palme J, Kristiansson E, Larsson DGJ. (2016). The structure and diversity of human, animal and environmental resistomes. Microbiome. 4:54. Flach CF, Johnning A, Nilsson I, Smalla K, Kristiansson E, Larsson DGJ. (2015) Isolation of novel IncA/C and IncN fluoroquinolone resistance plasmids from an antibiotic-polluted lake. Journal of Antimicrobial Chemotherapy 70:2709-2717. These factories produce the drugs we all use! Bengtsson-Palme J, Gunnarsson L, Larsson DGJ. 2018. Can branding and price of pharmaceuticals guide informed choices towards improved pollution control during manufacturing? Journal of Cleaner Production. 171:137-146. Picture by M Kumar, Associated Press Larsson DGJ and Fick J. 2009. Transparency throughout the production chain a way to reduce pollution from the manufacturing of pharmaceuticals. Regulatory Toxicology and Pharmacology. 53:161-163. Some environmental actions needed from the health care sector Industry: improve awareness, increase transparency, install technical measures to limit pollution Governments: regulate emissions when possible, provide fair economic incentives, i.e. revise the generic substitution system Health care providers: add effective environmental criteria during procurement! 4

Let s make a change! E-mail: Personal website: CARe website: joakim.larsson@fysiologi.gu.se http://www.biomedicine.gu.se/joakimlarsson www.care.gu.se 5