Urinary tract infections (UTIs) are the second most frequent type of infection observed in clinical practice. Gram-negative Enterobacteriaceae are common pathogens in UTIs. Excessive antibiotic use in humans and animals, poor infection control, and increased global travel have accelerated the spread of multidrug-resistant strains (MDR). Carbapenem antibiotics are commonly considered the last line of defense against MDR Gram-negative bacteria; however, their efficacy is now threatened by the increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE). This comprehensive review aims to explore the biological mechanisms underlying carbapenem resistance and to present a focus on therapeutic alternatives currently available for complicated UTIs (cUTIs). A comprehensive bibliographic search was conducted on the PubMed/MEDLINE, Scopus, and Web of Science databases in December 2023. The best evidence on the topic was selected, described, and discussed. Analyzed with particular interest were the clinical trials pivotal to the introduction of new pharmacological treatments in the management of complicated cUTIs. Additional suitable articles were collected by manually cross-referencing the bibliography of previously selected papers. This overview provides a current and comprehensive examination of the treatment options available for CRE infections, offering a valuable resource for understanding this constantly evolving public health challenge.
