Outbreak by KPC-62-producing ST307 Klebsiella pneumoniae isolates resistant to ceftazidime/avibactam and cefiderocol in a university hospital in Madrid, Spain
Authors
Pablo Sánchez, Raúl DeIdentifiers
Permanent link (URI): http://hdl.handle.net/10017/59518DOI: 10.1093/jac/dkad086
ISSN: 0305-7453
Date
2023-05-03Embargo end date
2024-05-03Affiliation
Universidad de Alcalá. Departamento de Medicina y Especialidades Médicas. Unidad Docente de MedicinaFunders
Ministerio de Industria, Comercio y Competitividad
Instituto de Salud Carlos III
FEDER
Bibliographic citation
Journal of Antimicrobial Chemotherapy, 2023, v. 78, n. 5, p. 1259-1264
Keywords
Klebsiella pneumoniae ST307
KPC-62
Ceftazidime Avibacta m
Cefiderocol
Description / Notes
8 p.
Project
REIPI RD16/0016/0011 ; PI22/01283 ; CB21/13/00084
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/acceptedVersion
Rights
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/embargoedAccess
Abstract
Objectives: Ceftazidime/avibactam and cefiderocol are two of the latest antibiotics with activity against a wide variety of Gram-negatives, including carbapenem-resistant Enterobacterales. We sought to describe the phenotypic and genotypic characteristics of ceftazidime/avibactam- and cefiderocol-resistant KPC-Klebsiella pneumoniae (KPC-Kp) detected during an outbreak in 2020 in the medical ICU of our hospital.
Methods: We collected 11 KPC-Kp isolates (6 clinical; 5 surveillance samples) resistant to ceftazidime/avibactam and cefiderocol from four ICU patients (November 2020 to January 2021), without prior exposure to these agents. All patients had a decontamination regimen as part of the standard ICU infection prevention protocol. Additionally, one ceftazidime/avibactam- and cefiderocol-resistant KPC-Kp (June 2019) was retrospectively recovered. Antibiotic susceptibility was determined by broth microdilution. β-Lactamases were characterized and confirmed. WGS was also performed.
Results: All KPC-Kp isolates (ceftazidime/avibactam MIC ≥16/4 mg/L; cefiderocol MIC ≥4 mg/L) were KPC + CTX-M-15 producers and belonged to the ST307 high-risk-clone (ST307-HRC). KPC-62 (L168Q) was detected in all isolates involved in the 2020 outbreak, contained in January 2021. KPC-31 (D179Y) was identified in the KPC-Kp from 2019. Cloning experiments demonstrated that both blaKPC-62 and blaKPC-31 were responsible for ceftazidime/avibactam resistance (MIC >16 mg/L) and an increased cefiderocol MIC. Additionally, mutations in OmpA and EnvZ/OmpR porin proteins (in KPC-62-Kp) and in PBP2 (in KPC-31-Kp) were found and may be involved in cefiderocol resistance.
Conclusions: The emergence of resistance to both ceftazidime/avibactam and cefiderocol in KPC-Kp-HRCs, together with the diversification of novel KPC enzymes displaying different antibiotic resistance phenotypes, is an epidemiological and clinical risk.
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