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. 2025 Mar 15;12(4):ofaf164.
doi: 10.1093/ofid/ofaf164. eCollection 2025 Apr.

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

Federico Becerra-Aparicio  1 , Silvia Gómez-Zorrilla  2   3 , Marta Hernández-García  1   3 , Kyriaki Xanthopoulou  4   5 , Desiré Gijón  1 , Ana Siverio  2   6 , Dàmaris Berbel  7 , Emilia Cercenado  8   9 , Alba Rivera  10 , Ana De Malet  11 , Mariona Xercavins  12 , Enrique Ruiz De Gopegui  3   13 , Luis Canoura-Fernández  14 , José Antonio Martínez  15 , Cristina Seral  3   16 , José Luis Del Pozo  17 , Manuel Cotarelo  18 , Ricardo Ponz  18 , Paul G Higgins  4   5 , Xavier Durán-Jordà  19 , Rafael Cantón  1   3 , Antonio Oliver  3   13 , Juan Pablo Horcajada  2   3 , Patricia Ruiz-Garbajosa  1   3
Affiliations

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

Federico Becerra-Aparicio et al. Open Forum Infect Dis. .

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.

Keywords: Klebsiella pneumoniae; ST307 clone; carbapenemase-producing Enterobacterales; extended-spectrum β-lactamases; health care–associated infections.

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Conflict of interest statement

Potential conflicts of interest. E. C. has received payment honoraria for educational activities from MSD, Shinogi, and Pfizer. E. R. D. G. has received support for attending meetings from Becton Dickinson. R. P. and M. C. work as MSD Spain full-time employees. A. O. has received honoraria for educational activities and consulting fees from MSD, Shinogi, and Pfizer. J. P. H. has received research grants from MSD; consulting fees from MSD, Pfizer, Menarini, Angelini, Zambon, and Tillots; honoraria for educational activities from Pfizer, MSD, and Angelini; and support for attending meetings from MSD and Pfizer. J. P. H. has also participated on a data safety monitoring board from TFT Pharmaceuticals. P. R.-G. has received support for attending meetings from MSD. R. C. has received research grants from MSD and Shionogi. All other authors report no potential conflicts.

Figures

Figure 1.
Figure 1.
Similarity tree of sequenced Klebsiella pneumoniae complex isolates (n = 55) during the ITUBRAS-2 project and visualized with iTOL. Branch length is indicative of the MASH distance. Antimicrobial susceptibility results and molecular and epidemiologic data are also included. AMC, amoxicillin/clavulanic acid; AMK, amikacin; AZT, aztreonam; CIP, ciprofloxacin; COL, colistin; C/T, ceftolozane/tazobactam; ERT, ertapenem; FEP, cefepime; FOT, cefotaxime; GEN, gentamicin; IMP, imipenem; MER, meropenem; PTZ, piperacillin-tazobactam; STX, trimethoprim/sulfamethoxazole; TAZ, ceftazidime; TOB, tobramycin. I, susceptible–increase exposure; R, resistant; S, susceptible–standard dose.
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