Published Paper Details:

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical threat to global health, as it poses severe challenges to clinical treatment and infection control. This review explores the genetic basis of carbapenem resistance in Klebsiella pneumoniae, elucidating the mechanisms that enable this pathogen to withstand last-resort antibiotics and complicate patient management. Klebsiella pneumoniae, a prominent member of the Enterobacteriaceae family, is responsible for a broad spectrum of nosocomial infections, including urinary tract infections, pneumonia, and sepsis. The increasing prevalence of CRKP, characterized by its resistance to carbapenems such as imipenem, meropenem, and doripenem, underscores the necessity for an in-depth understanding of its genetic determinants and epidemiology. The primary mechanism of carbapenem resistance in K. pneumoniae is the production of carbapenemases, which are ?-lactamase enzymes that hydrolyze carbapenems, rendering them ineffective. This review highlights key resistance genes, including blaKPC, blaNDM, and blaOXA-48-like, each belonging to different Ambler classes of carbapenemases. The blaKPC gene, part of the Ambler class A serine ?-lactamases, is notorious for its global dissemination and significant role in CRKP outbreaks. Meanwhile, blaNDM (New Delhi metallo-?-lactamase), a class B metallo-?-lactamase, further complicates treatment by degrading a wide range of ?-lactams. The blaOXA-48-like genes, classified under Ambler class D oxacillinases, are often associated with multidrug-resistant strains and are a growing concern for healthcare settings. Diagnostic methods for CRKP rely on molecular techniques such as PCR, whole-genome sequencing (WGS), and pulsed-field gel electrophoresis (PFGE), which facilitate the rapid identification and tracking of resistant strains. However, the limitations of current diagnostic capabilities highlight the need for ongoing improvements to ensure timely and accurate detection. In light of limited treatment options, alternative therapeutic strategies have emerged, including novel antibiotics and combination therapies. Ceftazidime-avibactam, aztreonam-avibactam, and fosfomycin present promising alternatives, particularly against carbapenemase-producing isolates. Furthermore, combination therapies utilizing colistin, tigecycline, and other agents show potential in overcoming resistance, though their application requires careful consideration to prevent further resistance development. The development of effective surveillance systems, coupled with strategic interventions, offers hope for controlling the spread of CRKP and ensuring the efficacy of future treatment paradigms.