CTX-M β-lactamases are a key example of antibiotic resistance evolution. These enzymes originate from chromosomal genes in Kluyvera species, which are mobilized into mobile genetic elements like insertion sequences (ISEcp1, ISCR1) and integrons. This process has occurred multiple times, leading to different CTX-M clusters. The spread of these enzymes is driven by genetic mobilization and antibiotic selective pressure, particularly from cephalosporins like cefotaxime and ceftazidime, which promote mutations and diversification. CTX-M enzymes have become globally prevalent, especially in Enterobacteriaceae, and are associated with multi-drug resistant clones. They are often found in epidemic plasmids and have been linked to carbapenemase production, contributing to a complex pandemic scenario. CTX-M enzymes have spread worldwide, with CTX-M-15 being particularly widespread. They have been identified in various countries, including Europe, South America, and Asia, and have been found in both clinical and environmental settings. CTX-M enzymes are not limited to Enterobacteriaceae but have also been found in non-fermentative bacteria like Pseudomonas aeruginosa and Stenotrophomonas maltophilia. The origin of CTX-M genes is linked to Kluyvera species, and their mobilization is facilitated by insertion sequences. The evolution of CTX-M enzymes has been influenced by selective pressures, including the use of antibiotics and the presence of other resistance genes. The spread of CTX-M enzymes is also influenced by genetic elements like integrons and transposons, which facilitate their dissemination. The diversity of CTX-M enzymes has increased significantly, with new variants emerging through mutations and recombination events. These enzymes have also been associated with resistance to β-lactam-β-lactamase inhibitors and carbapenems, highlighting their adaptability and the challenges they pose in clinical settings. The genetic environments of CTX-M genes are complex, involving various mobile genetic elements that contribute to their spread and maintenance. The mobilization of CTX-M genes is a key factor in their global spread, and understanding their origin and evolution is crucial for developing strategies to combat antibiotic resistance.CTX-M β-lactamases are a key example of antibiotic resistance evolution. These enzymes originate from chromosomal genes in Kluyvera species, which are mobilized into mobile genetic elements like insertion sequences (ISEcp1, ISCR1) and integrons. This process has occurred multiple times, leading to different CTX-M clusters. The spread of these enzymes is driven by genetic mobilization and antibiotic selective pressure, particularly from cephalosporins like cefotaxime and ceftazidime, which promote mutations and diversification. CTX-M enzymes have become globally prevalent, especially in Enterobacteriaceae, and are associated with multi-drug resistant clones. They are often found in epidemic plasmids and have been linked to carbapenemase production, contributing to a complex pandemic scenario. CTX-M enzymes have spread worldwide, with CTX-M-15 being particularly widespread. They have been identified in various countries, including Europe, South America, and Asia, and have been found in both clinical and environmental settings. CTX-M enzymes are not limited to Enterobacteriaceae but have also been found in non-fermentative bacteria like Pseudomonas aeruginosa and Stenotrophomonas maltophilia. The origin of CTX-M genes is linked to Kluyvera species, and their mobilization is facilitated by insertion sequences. The evolution of CTX-M enzymes has been influenced by selective pressures, including the use of antibiotics and the presence of other resistance genes. The spread of CTX-M enzymes is also influenced by genetic elements like integrons and transposons, which facilitate their dissemination. The diversity of CTX-M enzymes has increased significantly, with new variants emerging through mutations and recombination events. These enzymes have also been associated with resistance to β-lactam-β-lactamase inhibitors and carbapenems, highlighting their adaptability and the challenges they pose in clinical settings. The genetic environments of CTX-M genes are complex, involving various mobile genetic elements that contribute to their spread and maintenance. The mobilization of CTX-M genes is a key factor in their global spread, and understanding their origin and evolution is crucial for developing strategies to combat antibiotic resistance.