Whole Genome Sequencing Analysis of Klebsiella pneumoniae Isolates from Health Care-Associated Bacteremia of Urinary Origin in Spain: Findings from the Multicenter ITUBRAS-2 Cohort Study

Abstract

Background: The objective of this study was to assess the microbiological and clinical features of Klebsiella pneumoniae health care-associated bacteremia of urinary origin (HCA-BUO) in Spain, with a focus on third-generation cephalosporin-(3GCR-Kp) and carbapenem-resistant K pneumoniae (CR-Kp) isolates. Methods: A total of 96 (21.4%, 96/449) K pneumoniae blood isolates were prospectively collected from patients with HCA-BUO (n = 443) from 12 tertiary care hospitals in Spain (2017-2019). Antimicrobial susceptibility was determined (standard broth microdilution), and extended-spectrum β-lactamase, AmpC, and carbapenemase production was screened. A subset of 55 K pneumoniae isolates was analyzed by whole genome sequencing (Illumina) to determine population structure, resistome, and virulome. Additionally, 13 of these isolates were subjected to long-read sequencing (Nanopore) for plasmid characterization. Patients' baseline and clinical characteristics were reviewed. Results: 3GCR-Kp prevalence was 43.8% (42/96), mostly associated with extended-spectrum β-lactamase production (34/96, 35.4%; mainly CTX-M-15, 32/34, 94.1%) and the dissemination of sequence type (ST)-307 (15/34, 44.1%) and other globally spread multidrug-resistant high-risk clones. CR-Kp prevalence was 9.4% (9/96); all isolates belonged to different STs and were mostly associated with carbapenemase production (6/9, 66.7%; mainly OXA-48-like, n = 3). Additionally, 3GCR-Kp and CR-Kp isolates showed higher content of other antibiotic resistance genes. Altogether, these episodes were associated with prior antibiotic use and receipt of inadequate empirical treatment. Conclusions: There is a high prevalence of 3GCR and CR-Kp causing HCA-BUO in Spain, mainly driven by the dissemination of ST307/CTX-M-15 and other globally spread multidrug-resistant high-risk clones, challenging the selection of empirical and targeted treatments for these infections.