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

• Published in: Infectious diseases and therapy Vol. 12; no. 5; pp. 1319 - 1335
• Main Authors: Manesh, Abi, Shankar, Chaitra, George, Mithun M., Jasrotia, Davinder S., Lal, Binesh, George, Biju, Mathews, Vikram, Eapen, C. E., Joseph, Philip, Subramani, K., Rao, Shoma, Peter, John V., Chacko, Binila, Zachariah, Anand, Sathyendra, Sowmya, Hansdak, Samuel G., Abraham, Ooriapadickal C., Iyadurai, Ramya, Vijayakumar, Saranya, Karthik, Rajiv, Marwick, Charis A., Parcell, Benjamin J., Gilbert, Ian H., Veeraraghavan, Balaji, Varghese, George M.
• Format: Journal Article
• Language: English
• Published: Cheshire Springer Healthcare 01.05.2023; Springer; Springer Nature B.V; Adis, Springer Healthcare
• Subjects: Antibiotics; Bacteremia; Bacterial pneumonia; Beta lactamases; Carbapenem resistant; Cohort analysis; DNA sequencing; Drug resistance in microorganisms; Genetic aspects; Genetic diversity; Genomes; Genomics; Health aspects; Imipenem; India; Infectious Diseases; Internal Medicine; Klebsiella pneumoniae; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Mortality; Nucleotide sequencing; Original Research; Pneumonia; Temporal evolution; United Kingdom; Virulence (Microbiology); United Kingdom; India; Temporal evolution; Carbapenem resistant; Bacteremia; Klebsiella pneumoniae
• ISSN: 2193-8229; 2193-6382
• DOI: 10.1007/s40121-023-00803-3

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.