Clinical and Genomic Evolution of Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections over Two Time Periods at a Tertiary Care Hospital in South India: A Prospective Cohort Study

Abi Manesh, Chaitra Shankar, Mithun M. George, Davinder S. Jasrotia, Binesh Lal, Biju George, Vikram Mathews, C. E. Eapen, Philip Joseph, K. Subramani, Shoma Rao, John V. Peter, Binila Chacko, Anand Zachariah, Sowmya Sathyendra, Samuel G. Hansdak, Ooriapadickal C. Abraham, Ramya Iyadurai, Saranya Vijayakumar, Rajiv KarthikCharis A. Marwick, Benjamin J. Parcell, Ian H. Gilbert, Balaji Veeraraghavan*, George M. Varghese*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Introduction: The objective of this study was to examine the evolution of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections and their impact at a tertiary care hospital in South India. Methods: A comparative analysis of clinical data from two prospective cohorts of patients with CRKp bacteremia (C1, 2014–2015; C2, 2021–2022) was carried out. Antimicrobial susceptibilities and whole genome sequencing (WGS) data of selected isolates were also analyzed. Results: A total of 181 patients were enrolled in the study, 56 from C1 and 125 from C2. CRKp bacteremia shifted from critically ill patients with neutropenia to others (ICU stay: C1, 73%; C2, 54%; p = 0.02). The overall mortality rate was 50% and the introduction of ceftazidime-avibactam did not change mortality significantly (54% versus 48%; p = 0.49). Oxacillinases (OXA) 232 and 181 were the most common mechanisms of resistance. WGS showed the introduction of New Delhi metallo-β-lactamase-5 (NDM-5), higher genetic diversity, accessory genome content, and plasmid burden, as well as increased convergence of hypervirulence and carbapenem resistance in C2. Conclusions: CRKp continues to pose a significant clinical threat, despite the introduction of new antibiotics. The study highlights the evolution of resistance and virulence in this pathogen and the impact on patient outcomes in South India, providing valuable information for clinicians and researchers.

Original languageEnglish
Pages (from-to)1319-1335
Number of pages17
JournalInfectious Diseases and Therapy
Issue number5
Publication statusPublished - May 2023


  • Bacteremia
  • Carbapenem resistant
  • Klebsiella pneumoniae
  • Temporal evolution

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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