Comparison of different approaches to antibiotic restriction in food-producing animals: stratified results from a systematic review and meta-analysis

BACKGROUND: We have previously reported, in a systematic review of 181 studies, that restriction of antibiotic use in food-producing animals is associated with a reduction in antibiotic-resistant bacterial isolates. While informative, that report did not concretely specify whether different types of restriction are associated with differential effectiveness in reducing resistance. We undertook a sub-analysis of the systematic review to address this question. METHODS: We created a classification scheme of different approaches to antibiotic restriction: (1) complete restriction; (2) single antibiotic-class restriction; (3) single antibiotic restriction; (4) all non-therapeutic use restriction; (5) growth promoter and prophylaxis restriction; (6) growth promoter restriction and (7) other/undetermined. All studies in the original systematic review that were amenable to meta-analysis were included into this substudy and coded by intervention type. Meta-analyses were conducted using random effects models, stratified by intervention type. RESULTS: A total of 127 studies were included. The most frequently studied intervention type was complete restriction (n=51), followed by restriction of non-therapeutic (n=33) and growth promoter (n=19) indications. None examined growth promoter and prophylaxis restrictions together. Three and seven studies examined single antibiotic-class and single antibiotic restrictions, respectively; these two intervention types were not significantly associated with reductions in antibiotic resistance. Though complete restrictions were associated with a 15% reduction in antibiotic resistance, less prohibitive approaches also demonstrated reduction in antibiotic resistance of 9%–30%. CONCLUSION: Broad interventions that restrict global antibiotic use appear to be more effective in reducing antibiotic resistance compared with restrictions that narrowly target one specific antibiotic or antibiotic class. Importantly, interventions that allow for therapeutic antibiotic use appear similarly effective compared with those that restrict all uses of antibiotics, suggesting that complete bans are not necessary. These findings directly inform the creation of specific policies to restrict antibiotic use in food-producing animals.