TY - JOUR
T1 - Clinical and genomic evolution of carbapenem-resistant klebsiella pneumoniae bloodstream infections over two time periods at a tertiary care hospital in South India
T2 - A prospective cohort study
AU - Manesh, Abi
AU - Shankar, Chaitra
AU - George, Mithun M.
AU - Jasrotia, Davinder S.
AU - Lal, Binesh
AU - George, Biju
AU - Mathews, Vikram
AU - Eapen, C. E.
AU - Joseph, Philip
AU - Subramani, K.
AU - Rao, Shoma
AU - Peter, John V.
AU - Chacko, Binila
AU - Zachariah, Anand
AU - Sathyendra, Sowmya
AU - Hansdak, Samuel G.
AU - Abraham, Ooriapadickal C.
AU - Iyadurai, Ramya
AU - Vijayakumar, Saranya
AU - Karthik, Rajiv
AU - Marwick, Charis A.
AU - Parcell, Benjamin J.
AU - Gilbert, Ian H.
AU - Veeraraghavan, Balaji
AU - Varghese, George M.
N1 - Funding Information:
This study is supported by the institutional research grant of Christian Medical College, Vellore, University of Dundee, and International Society for Infectious Diseases. The publication fee was waived.
Copyright:
© 2023. The Author(s).
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - Bacteremia
KW - Carbapenem resistant
KW - Klebsiella pneumoniae
KW - Temporal evolution
UR - http://www.scopus.com/inward/record.url?scp=85153056134&partnerID=8YFLogxK
U2 - 10.1007/s40121-023-00803-3
DO - 10.1007/s40121-023-00803-3
M3 - Article
C2 - 37062023
SN - 2193-8229
VL - 12
SP - 1319
EP - 1335
JO - Infectious Diseases and Therapy
JF - Infectious Diseases and Therapy
IS - 5
ER -
