Simple SummaryFosfomycin is an antibiotic with renewed interest over the last years, especially in human medicine, as it possesses some advantageous properties and a broad spectrum of bactericidal activity. Moreover, the emerging issue of multi-resistance against traditional antibiotics obligates specialists to turn to new alternative agents. However, cases of Fosfomycin-resistant strains are being detected at a rising rate worldwide, among humans and animals. The objective of this review is to collect, present and analyze studies related to Fosfomycin resistance in isolates from companion animals and specifically dogs and cats. Variable articles were collected and data for the relevant strains were scanned and evaluated. Since Fosfomycin is an agent not routinely used by veterinarians, the detection of Fosfomycin-resistant strains in canine and feline samples indicates possible dissemination of these strains among humans, pets, and the environment, reinforced by other factors. Concerning the origin, the species, and the resistance patterns of the related bacteria, useful conclusions were drawn, about the presence, the spreading, and possibly the causes of Fosfomycin resistance among companion animals and between them and their environment.AbstractFosfomycin is an old antibacterial agent, which is currently used mainly in human medicine, in uncomplicated Urinary Tract Infections (UTIs). The purpose of this review is to investigate the presence and the characteristics of Fosfomycin resistance in bacteria isolated from canine or feline samples, estimate the possible causes of the dissemination of associated strains in pets, and underline the requirements of prospective relevant studies. Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines were used for the search of current literature in two databases. A total of 33 articles were finally included in the review. Relevant data were tracked down, assembled, and compared. Referring to the geographical distribution, Northeast Asia was the main area of origin of the studies.E. coliwas the predominant species detected, followed by other Enterobacteriaceae, Staphylococci, andPseudomonasspp.FosAandfosA3were the more frequently encountered Antimicrobial Resistance Genes (ARGs) in the related Gram-negative isolates, whilefosBwas regularly encountered in Gram-positive ones. The majority of the strains were multidrug-resistant (MDR) and co-carried resistance genes against several classes of antibiotics and especially β-Lactams, such asblaCTX-MandmecA. These results demonstrate the fact that the cause of the spreading of Fosfomycin-resistant bacteria among pets could be the extended use of other antibacterial agents, that promote the prevalence of MDR, epidemic strains among an animal population. Through the circulation of these strains into a community, a public health issue could arise. Further research is essential though, for the comprehensive consideration of the issue, as the current data are limited.