Effectiveness of antimicrobial interventions directed at tackling antimicrobial resistance in animal production: A systematic review and meta-analysis

Background: In the last decades, a more prudent and rational use of antimicrobials has been progressively directed towards animal production to reduce antimicrobial selective pressure and antimicrobial resistance (AMR) in microorganisms and safeguard the antimicrobial efficacy of treatments in human medicine. This systematic review evaluated the effectiveness of interventions that have been applied to reduce or improve veterinary antimicrobial usage and aimed at decreasing resistant bacteria in chicken broiler and pig production contexts.Methods: Original articles were identified by searching PubMedTM, ScopusTM, The Cochrane LibraryTM, and Web of ScienceTM, and grey literature by searching DANS EASYTM, WorldCatTM and RCAAPTM. Inclusion criteria included: chicken broiler or pig populations (predestined for meat production), interventions intended to reduce/ improve antimicrobial use, comparator with standard or no use of antimicrobials, outcomes related to prevalence of resistant bacteria, farm level studies, original data, and analytical observational studies. Data was extracted from eligible studies and meta-analysis using random or fixed effects models was conducted for combinations including type of intervention, bacterial species, production type and animal populations. Models were selected according to heterogeneity between studies. The effectiveness of interventions was assessed using pooled odds ratio of resistance to antimicrobial substances/classes by bacteria for associations between animal populations with and without intervention. Results: A total of 46 studies were eligible for review. For chicken broilers, most interventions were identified as antimicrobial restrictions on all non-therapeutic use (46%), complete restriction (27%), and prohibition on antimicrobials used for growth promotion (23%). As for pig populations, restrictions were mainly observed on all non-therapeutic use (37%), complete restriction (37%) and group treatments (22%). For meta-analysis, 21 studies were pooled after assessment of existing combinations. These combinations demonstrated a protective effect for most antimicrobial classes in Escherichia coli, Campylobacter and Enterococcus isolates from samples of chicken broilers as well in Escherichia coli and Campylobacter spp. from samples of pigs, compared to animals raised under conventional production or without intervention. Increased odds of resistance were only observed for cephalosporins in E. coli and broilers raised without antimicrobials, and to fluoroquinolones and quinolones in Campylobacter and pigs raised without antimicrobials, compared to conventional production. Conclusions: Our study indicates that organic production, antimicrobial-free farms, and group treatment restrictions are recommended for AMR reduction, providing information that may support decision-making to tackle AMR and better reporting to improve comparability of results between studies.