Carbapenemase-producing Enterobacteriaceae (CPE) are a growing global health threat, primarily caused by Klebsiella pneumoniae and other bacteria producing enzymes like KPC, MβLs, and OXA-48. These enzymes confer resistance to carbapenems, leading to severe infections in immunocompromised patients with high mortality rates. CPE has spread globally, with KPC-producing strains first emerging in the U.S. and later in Latin America, Israel, and other regions. MβLs, including VIM, IMP, and NDM types, are also widespread, while OXA-48 is prevalent in various Enterobacteriaceae. Detection methods include phenotypic tests like MHT, chelating agents, and molecular techniques such as PCR and mass spectrometry. Antimicrobial agents like colistin, tigecycline, and fosfomycin show some efficacy, but resistance is increasing. In vitro studies suggest synergistic effects between polymyxins, carbapenems, and other agents. Experimental models indicate that optimized carbapenem regimens can achieve bactericidal effects in some cases. Despite these findings, the lack of effective treatments and the spread of CPE necessitate improved infection control, judicious antimicrobial use, and the development of novel agents. The global crisis demands urgent action to prevent further spread and improve patient outcomes.Carbapenemase-producing Enterobacteriaceae (CPE) are a growing global health threat, primarily caused by Klebsiella pneumoniae and other bacteria producing enzymes like KPC, MβLs, and OXA-48. These enzymes confer resistance to carbapenems, leading to severe infections in immunocompromised patients with high mortality rates. CPE has spread globally, with KPC-producing strains first emerging in the U.S. and later in Latin America, Israel, and other regions. MβLs, including VIM, IMP, and NDM types, are also widespread, while OXA-48 is prevalent in various Enterobacteriaceae. Detection methods include phenotypic tests like MHT, chelating agents, and molecular techniques such as PCR and mass spectrometry. Antimicrobial agents like colistin, tigecycline, and fosfomycin show some efficacy, but resistance is increasing. In vitro studies suggest synergistic effects between polymyxins, carbapenems, and other agents. Experimental models indicate that optimized carbapenem regimens can achieve bactericidal effects in some cases. Despite these findings, the lack of effective treatments and the spread of CPE necessitate improved infection control, judicious antimicrobial use, and the development of novel agents. The global crisis demands urgent action to prevent further spread and improve patient outcomes.