How effective are strategies to control the dissemination of antibiotic resistance in the environment? A systematic review
Authors: Goulas Anaïs , Belhadi Drifa , Descamps Alexandre , Andremont Antoine , Benoit Pierre , Courtois Sophie , Dagot Christophe , Grall Nathalie , Makowski David , Nazaret Sylvie , Nélieu Sylvie , Patureau Dominique , Petit Fabienne , Roose-Amsaleg Céline , Vittecoq Marion , Livoreil Barbara , Laouénan Cédric 
Published: February 2020

Abstract
Background
Antibiotic resistance is a major concern for public and environmental health. The role played by the environment in disseminating resistance is increasingly considered, as well as its capacity for mitigation. We reviewed the literature on strategies to control dissemination of antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARG) and mobile genetic elements (MGE) in the environment.

Methods
This systematic review focused on three main strategies: (i) restriction of antibiotic use (S1), (ii) treatments of liquid/solid matrices (S2) and (iii) management of natural environment (S3). Articles were collected from seven scientific databases until July 2017 and from Web of Science until June 2018. Only studies reporting measurements of ARB, ARG or MGE in environmental samples were included. An evidence map was drawn from metadata extracted from all studies eligible for S1, S2 and S3. Subsets of studies were assessed for internal and external validity to perform narrative and quantitative syntheses. A meta-analysis was carried out to assess the effects of organic waste treatments (random-effect models).

Review findings
Nine hundred and thirty-one articles representing 1316 individual studies (n) were eligible for S1 (n = 59), S2 (n = 781) and S3 (n = 476) strategies, respectively. Effects of interventions to control the dissemination of antibiotic resistance in the environment were primarily studied in strategy S2. A partial efficiency of wastewater treatment plants (WWTPs) to reduce antibiotic resistance in treated effluent was reported in 118 high validity studies. In spite of the heterogeneity in published results, the meta-analysis showed that composting and drying were efficient treatments to reduce the relative abundance of ARG and MGE in organic waste, by 84% [65%; 93%] and 98% [80%; 100%], respectively. The effect of anaerobic digestion was not statistically significant (51% reduction [− 2%; 77%]) when organic waste treatments were compared together in the same model. Studies in strategies S1 and S3 mainly assessed the effects of exposure to sources of contamination. For instance, 28 medium/high validity studies showed an increase of antibiotic resistance in aquatic environments at the WWTP discharge point. Some of these studies also showed a decrease of resistance as the distance from the WWTP increases, related to a natural resilience capacity of aquatic environments. Concerning wildlife, nine medium/high validity studies showed that animals exposed to anthropogenic activities carried more ARB.

Conclusions and implications
Knowledge gaps were identified for the relationship between restriction of antibiotic use and variation of antibiotic resistance in the environment, as well as on possible interventions in situ in natural environment. Organic waste treatments with thermophilic phase (> 50 °C) should be implemented before the use/release of organic waste in the environment. More investigation should be conducted with the datasets available in this review to determine the treatment efficiency on ARG carried by specific bacterial communities.