Urinary tract infections (UTIs) represent frequently recorded bacterial infections worldwide, predominantly caused by Escherichia coli. Amikacin, an aminoglycoside antibiotic, has historically been proven therapeutic approach for severe UTIs, especially when resistance to other antibiotics is a concern. However, the emergence and spread of amikacin resistance in Uropathogenic Escherichia coli (UPEC) strains have raised significant clinical challenges. The amikacin resistance mechanisms in UTIs, mainly the molecular mechanisms behind resistance development, the prevalence and distribution of amikacin-resistant UPEC strains in different age groups also should be considered. Resistance to amikacin in UPEC often arises due to aminoglycoside-modifying enzymes, efflux pumps, or alterations in the bacterial ribosomal target sites. These resistance mechanisms may be intrinsic or procured through horizontal gene exchange, further complicating treatment options. The prevalence of amikacin-resistant UPEC strains in UTIs is considerably increasing. Since Amikacin is the important and primary therapeutic option of various pathogenic UTIs including other multidrug resistance strains such as ESBL producers, the development of Amikacin resistance should be taken into account as a dangerous scenario. © 2025 Elsevier B.V., All rights reserved.