ملخص
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.
| اللغة الأصلية | English |
|---|---|
| الصفحات (من إلى) | 1319-1335 |
| عدد الصفحات | 17 |
| دورية | Infectious Diseases and Therapy |
| مستوى الصوت | 12 |
| رقم الإصدار | 5 |
| المعرِّفات الرقمية للأشياء | |
| حالة النشر | Published - مايو 2023 |
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في: Infectious Diseases and Therapy, المجلد 12, رقم 5, ٠٥.٢٠٢٣, صفحة 1319-1335.
نتاج البحث: المساهمة في مجلة › Article › مراجعة النظراء
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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. Funding Information: We are grateful for the patients and medical personnel involved in this study. 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. George M Varghese, Balaji Veeraraghavan, Ian H. Gilbert, and Abi Manesh conceptualized the study and developed the study protocol. George M Varghese, Balaji Veeraraghavan, Abi Manesh, Chaitra Shankar, and Davinder Singh Jasrotia developed the methodology. George M Varghese and Abi Manesh acquired funding. George M Varghese, Balaji Veeraraghavan, Abi Manesh, Davinder Singh Jasrotia, Mithun Mohan George, Saranya Vijayakumar and Chaitra Shankar provided oversight and supervision. Mithun Mohan George did the statistical analysis. Davinder Singh Jasrotia and Mithun Mohan George did project administration, oversaw data collection and management. Chaitra Shankar, Abi Manesh, Balaji Veeraraghavan, George M Varghese, and Mithun Mohan George accessed and verified the data. George M Varghese, Abi Manesh, Chaitra Shankar, and Mithun Mohan George wrote the original draft of the manuscript. Balaji Veeraraghavan, Davinder Singh Jasrotia, Binesh Lal, Biju George, Vikram Mathews, C.E. Eapen, Philip Joseph, K Subramani, Shoma Rao, John Victor Peter, Binila Chacko, Anand Zachariah, Sowmya Sathyendra, Samuel George Hansdak, Ooriapadickal Cherian Abraham, Ramya Iyadurai, Saranya Vijayakumar, Rajiv Karthik, Charis A Marwick, Benjamin J Parcell, and Ian H. Gilbert provided critical review and edited the original draft. All authors had access to the raw data, reviewed and approved the final manuscript, and agreed to the submission for publication. Abi Manesh, Chaitra Shankar, Mithun Mohan George, Davinder Singh Jasrotia, Binesh Lal, Biju George, Vikram Mathews, C.E. Eapen, Philip Joseph, K Subramani, Shoma Rao, John Victor Peter, Binila Chacko, Anand Zachariah, Sowmya Sathyendra, Samuel George Hansdak, Ooriapadickal Cherian Abraham, Ramya Iyadurai, Saranya Vijayakumar, Rajiv Karthik, Charis A Marwick, Benjamin J Parcell, Ian H. Gilbert, Balaji Veeraraghavan, and George M Varghese have nothing to disclose. The study was conducted according to the principles of the Helsinki Declaration and was approved by the Institutional Review Board and Ethics Committee of Christian Medical College, Vellore (IRB No.9041/2014 and IRB No.13464/2020). Before recruitment into the study, informed consent was obtained from all the patients or immediate kin for accessing clinical information and publishing data. The data sets generated and/or analysed during the current study are available from the corresponding author on reasonable request. Publisher 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
UR - http://www.scopus.com/inward/citedby.url?scp=85153056134&partnerID=8YFLogxK
U2 - 10.1007/s40121-023-00803-3
DO - 10.1007/s40121-023-00803-3
M3 - Article
C2 - 37062023
AN - SCOPUS:85153056134
SN - 2193-8229
VL - 12
SP - 1319
EP - 1335
JO - Infectious Diseases and Therapy
JF - Infectious Diseases and Therapy
IS - 5
ER -