A Systematic Review of the Effect of Macrolide Use in Food Producing Animals and its Impact on Rates of Human Carriage and Disease of Macrolide-Resistant Bacteria

Abstract

Layman's Summary: Campylobacteriosis is a common illness caused by Campylobacter spp.. which causes a global loss in nearly the in nearly 33 million healthy human life years globally annually (the World Health Organization (WHO)). The main antibiotics used to treat campylobacteriosis are macrolides, which are in the highest priority group on both the WHO’s Critically Important Antimicrobials list and the World Organization for Animal Health (WOAH) critically important veterinary antimicrobials list. Macrolides are important drugs to both human and animal health and are used to treat common illnesses where there are few alternatives. The WHO cites the burden of disease and evidence of macrolide resistance in Campylobacter species and resistance genes in Enterococcus species which could be transferred from animals to humans as reasons for macrolides' high ranking in both lists. This systematic review aims to examine whether use of macrolides in food animals impacts the rate of human carriage and disease by macrolide-resistant bacteria, namely Campylobacter species and Enterococcus species of bacteria. I divided this question into 5 sub-questions; 1) the first asks if the use of macrolides in food animals is associated with carriage of macrolide-resistant bacteria in these animals; and 2) if the presence of resistant bacteria in food animals leads to resistant bacteria in food; 3) next, whether macrolide resistant bacteria can be transmitted from animals to humans via occupational and 4) community exposure was analyzed; 5) finally, data was collected to investigate if the carriage of macrolide resistant bacteria leads to illness in people. I performed a systematic literature search of Scopus and Web of Science for articles published between 1999 and September 2022. Quantitative analysis was performed when there was enough data in a category to make comparisons, otherwise a qualitative analysis was done. 59 papers were included. More data was available to address the first 2 sub-questions posed in the review than for the last 3 questions which needed more human data. Much of the available information described Campylobacter in animals within the food chain. Additionally, when Campylobacter spp. isolates from along the food chain were analyzed, I found that along the “farm to fork'' continuum, there is an increasing difference in species prevalence with C. jejuni being the most dominant species in human samples. Further study in this area would be valuable to help us understand what causes this shift and to gain more insight into the origins of human infections. This review found significant gaps in our understanding of the impact of using macrolides in food animals. More research that includes human samples and studies that use genetic data to track whether bacteria taken from different sources are related would be useful. The available information may indicate that while regulations should be cautious and control macrolide use in animals, a complete ban may not be necessary. Other solutions such as strict biosecurity controls in food production and educating the public on ways to reduce their risk, can be included to tackle potential transfer of macrolide resistant bacteria and genes from animals to humans.