Project Abstract

The rapid emergence and widespread dissemination of antibiotic-resistant pathogens pose a significant threat to global public health. Klebsiella pneumoniae, a Gram-negative bacterium, has emerged as one of the most concerning multidrug-resistant (MDR) pathogens, causing a wide range of life-threatening infections, including pneumonia, bloodstream infections, and urinary tract infections. The increasing prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains, which are resistant to last-resort antibiotics, has further exacerbated the challenge of effectively managing Klebsiella infections. This project aims to comprehensively characterize the antibiotic resistance patterns in clinical isolates of Klebsiella pneumoniae collected from a tertiary care hospital. The specific objectives of the study are (1) to determine the prevalence of antibiotic resistance, including resistance to carbapenems, in Klebsiella pneumoniae isolates; (2) to identify the underlying genetic mechanisms responsible for the observed resistance profiles; and (3) to assess the clonal relatedness of the resistant isolates using molecular typing techniques. The study will be conducted in three phases. In the first phase, a collection of Klebsiella pneumoniae isolates will be obtained from the hospital's microbiology laboratory. The isolates will be subjected to antimicrobial susceptibility testing using standard broth microdilution or Kirby-Bauer disk diffusion methods to determine their resistance profiles against a panel of clinically relevant antibiotics, including carbapenems, cephalosporins, fluoroquinolones, and aminoglycosides. In the second phase, the genotypic mechanisms underlying the observed resistance phenotypes will be investigated. Polymerase chain reaction (PCR) and DNA sequencing techniques will be employed to detect the presence of common resistance genes, such as those encoding extended-spectrum beta-lactamases (ESBLs), carbapenemases, and other resistance determinants. Additionally, whole-genome sequencing (WGS) will be performed on a subset of the isolates to provide a comprehensive understanding of the genetic basis of antibiotic resistance in Klebsiella pneumoniae. The third phase of the project will focus on the molecular epidemiology of the resistant isolates. Techniques such as multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) will be used to assess the clonal relatedness of the Klebsiella pneumoniae isolates. This information will help identify the predominant circulating strains and potential transmission patterns within the hospital setting. The findings from this project will have significant implications for clinical practice and public health. The comprehensive characterization of antibiotic resistance patterns and the underlying genetic mechanisms will provide valuable insights into the evolving epidemiology of MDR Klebsiella pneumoniae. This knowledge can inform the development of more effective antibiotic stewardship strategies, guide the selection of appropriate empirical antimicrobial therapy, and support the implementation of targeted infection control measures to mitigate the spread of these resistant strains. Furthermore, the identification of prevalent clones and potential transmission dynamics can aid in the implementation of effective surveillance and outbreak management protocols within the healthcare setting. In conclusion, this project's findings will contribute to a better understanding of the antibiotic resistance landscape in Klebsiella pneumoniae and facilitate the development of more informed and targeted strategies to combat the growing threat of antimicrobial resistance in this important pathogen.

Project Overview