The article reviews the global crisis of carbapenemase-producing *Klebsiella pneumoniae* and other enterobacterial species, highlighting the evolution of antibiotic resistance and the emergence of multidrug-resistant (MDR) strains. *K. pneumoniae* has historically been a significant cause of community-acquired and nosocomial infections, but its epidemiology and spectrum of infections have changed dramatically since the 1970s. The bacterium has become a leading cause of nosocomial infections, with high carriage rates in patients and healthcare settings. The introduction of multidrug resistance plasmids, particularly those encoding extended-spectrum β-lactamases (ESBLs) and carbapenemases, has further exacerbated the problem. Carbapenemases, including class A KPC enzymes, class B metallo-β-lactamases (MBLs), and class D OXA-48 enzymes, have become the first-choice drugs for treating healthcare-associated infections caused by *K. pneumoniae*. The article discusses the genetic context, substrate spectra, and β-lactam resistance phenotypes of these enzymes, emphasizing their widespread dissemination and impact on infection control and treatment. The global spread of carbapenemase-producing enterobacteria (CPE) is discussed, focusing on the emergence and spread of KPC, MBL, and OXA-48 producers. The article details the epidemiological characteristics of these strains, including their international spread and the challenges posed by their multidrug resistance. Detection methods for carbapenemase production, such as modified Hodge tests, chelating agent tests, boronate-based assays, and molecular techniques, are reviewed. The in vitro activity of antimicrobials against CPE is examined, with colistin, tigecycline, and fosfomycin being the most effective drugs. The article also discusses the potential synergistic effects of combining different antimicrobials and the efficacy of various treatment regimens in clinical settings. The clinical outcomes of infections caused by CPE are analyzed, with combination therapies including carbapenems showing the highest success rates. The limited efficacy of tigecycline and the need for cautious use of colistin as a single agent are highlighted. The article concludes by emphasizing the critical need for timely, aggressive, and effective treatment of CPE infections, given the limited therapeutic options and the increasing resistance profiles of these pathogens.The article reviews the global crisis of carbapenemase-producing *Klebsiella pneumoniae* and other enterobacterial species, highlighting the evolution of antibiotic resistance and the emergence of multidrug-resistant (MDR) strains. *K. pneumoniae* has historically been a significant cause of community-acquired and nosocomial infections, but its epidemiology and spectrum of infections have changed dramatically since the 1970s. The bacterium has become a leading cause of nosocomial infections, with high carriage rates in patients and healthcare settings. The introduction of multidrug resistance plasmids, particularly those encoding extended-spectrum β-lactamases (ESBLs) and carbapenemases, has further exacerbated the problem. Carbapenemases, including class A KPC enzymes, class B metallo-β-lactamases (MBLs), and class D OXA-48 enzymes, have become the first-choice drugs for treating healthcare-associated infections caused by *K. pneumoniae*. The article discusses the genetic context, substrate spectra, and β-lactam resistance phenotypes of these enzymes, emphasizing their widespread dissemination and impact on infection control and treatment. The global spread of carbapenemase-producing enterobacteria (CPE) is discussed, focusing on the emergence and spread of KPC, MBL, and OXA-48 producers. The article details the epidemiological characteristics of these strains, including their international spread and the challenges posed by their multidrug resistance. Detection methods for carbapenemase production, such as modified Hodge tests, chelating agent tests, boronate-based assays, and molecular techniques, are reviewed. The in vitro activity of antimicrobials against CPE is examined, with colistin, tigecycline, and fosfomycin being the most effective drugs. The article also discusses the potential synergistic effects of combining different antimicrobials and the efficacy of various treatment regimens in clinical settings. The clinical outcomes of infections caused by CPE are analyzed, with combination therapies including carbapenems showing the highest success rates. The limited efficacy of tigecycline and the need for cautious use of colistin as a single agent are highlighted. The article concludes by emphasizing the critical need for timely, aggressive, and effective treatment of CPE infections, given the limited therapeutic options and the increasing resistance profiles of these pathogens.