Restricting the use of antibiotics in food-producing animals and its associations with antibiotic resistance in food-producing animals and human beings: a systematic review and meta-analysis

Abstract

Background: Antibiotic use in human medicine, veterinary medicine, and agriculture has been linked to the rise of antibiotic resistance globally. We did a systematic review and meta-analysis to summarise the effect that interventions to reduce antibiotic use in food-producing animals have on the presence of antibiotic-resistant bacteria in animals and in humans.

Methods: On July 14, 2016, we searched electronic databases (Agricola, AGRIS, BIOSIS Previews, CAB Abstracts, MEDLINE, Embase, Global Index Medicus, ProQuest Dissertations, Science Citation Index) and the grey literature. The search was updated on Jan 27, 2017. Inclusion criteria were original studies that reported on interventions to reduce antibiotic use in food-producing animals and compared presence of antibiotic-resistant bacteria between intervention and comparator groups in animals or in human beings. We extracted data from included studies and did meta-analyses using random effects models. The main outcome assessed was the risk difference in the proportion of antibiotic-resistant bacteria.

Findings: A total of 181 studies met inclusion criteria. Of these, 179 (99%) described antibiotic resistance outcomes in animals, and 81 (45%) of these studies were included in the meta-analysis. 21 studies described antibiotic resistance outcomes in humans, and 13 (62%) of these studies were included in the meta-analysis. The pooled absolute risk reduction of the prevalence of antibiotic resistance in animals with interventions that restricted antibiotic use commonly ranged between 10 and 15% (total range 0-39), depending on the antibiotic class, sample type, and bacteria under assessment. Similarly, in the human studies, the pooled prevalence of antibiotic resistance reported was 24% lower in the intervention groups compared with control groups, with a stronger association seen for humans with direct contact with food-producing animals.

Interpretation: Interventions that restrict antibiotic use in food-producing animals are associated with a reduction in the presence of antibiotic-resistant bacteria in these animals. A smaller body of evidence suggests a similar association in the studied human populations, particularly those with direct exposure to food-producing animals. The implications for the general human population are less clear, given the low number of studies. The overall findings have directly informed the development of WHO guidelines on the use of antibiotics in food-producing animals.

Funding: World Health Organization.

Figure 1

Flow diagram of the study selection process *160 studies were exclusively in animals; the other 19 studied antibiotic resistance in both human beings and animals and so are counted in both animal studies and human studies. †Two studies were exclusively in the human population; the other 19 studied antibiotic resistance in both human beings and animals and so are counted in both animal studies and human studies.

Figure 2

Forest plot of absolute risk differences of multi-drug resistance Differences are shown for Enterobacteriaceae isolates in (A) faecal and (B) meat samples. The references used have been provided in the appendix.

Figure 3

Forest plot of absolute risk differences of antibiotic resistance in humans The references used have been provided in the appendix.