| Summary: | <b>Background:</b> Antimicrobial resistance is a serious public-health problem throughout the world. <i>Escherichia coli</i>, the most common Gram-negative microorganism, has developed different resistance mechanisms, making treating infections difficult. Colistin is considered a last-resort drug in the treatment of infections caused by <i>E. coli</i>. Plasmid-mediated mobile-colistin-resistant (<i>mcr</i>) genes in <i>E. coli</i>, now disseminated globally, are considered a major public-health threat. Humans, chickens, and pigs are the main reservoirs for <i>E. coli</i> and the sources of antibiotic resistance. Hence, an up-to-date and precise estimate of the global prevalence of <i>mcr</i> resistance genes in these reservoirs is necessary to understand more precisely the worldwide spread and to more effectively implement control and prevention strategies. <b>Methodology</b>: Publications were identified in the PubMed database on the basis of the PRISMA guidelines. English full-text articles were selected from December 2014 to March 2021. Descriptive statistics and a meta-analysis were performed in Excel and R software, respectively. Colistin resistance was defined as the molecular-genetic detection of the <i>mcr</i> genes. The crude and estimated prevalence were calculated for each host and continent. The studies were divided into two groups; community-based when they involved isolates from healthy humans, chickens, or pigs, and clinical studies when they involved only hospital, outpatient, or laboratory isolates. <b>Results</b>: A total of 1278 studies were identified and 218 were included in this systematic review and meta-analysis, divided into community studies (159 studies) and clinical studies (59 studies). The general prevalence of <i>mcr</i>-mediated colistin-resistant <i>E. coli</i> (<b>mcrMCRE</b>) was 6.51% (n = 11,583/177,720), reported in 54 countries and on five continents; Asia with 119 studies followed by Europe with 61 studies registered the most articles. Asia reported the major diversity of <i>mcr</i>-variants (eight of nine, except <i>mcr-2</i>). Worldwide, chickens and pigs proved to be the principal reservoir of <i>mcr</i> with an estimated prevalence of 15.8% and 14.9%, respectively. Healthy humans and clinical isolates showed a lower prevalence with 7.4% and 4.2% respectively. <b>Conclusions</b>: In this systematic review and meta-analysis, the worldwide prevalence of <i>mcr</i> in <i>E. coli</i> isolated from healthy humans, chickens, and pigs was investigated. A wide prevalence and distribution of <i>mcr</i> genes was demonstrated on all continents in <i>E. coli</i> isolates from the selected reservoirs. Understanding the epidemiology and occurrence in the reservoirs of <i>mcr</i> in <i>E. coli</i> on different continents of the world facilitates tracing how <i>mcr</i> genes are transmitted and determining the infection risks for humans. This knowledge can be used to reduce the incidence of zoonotic transmission by implementing the appropriate control programs.
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