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. 2024 Sep:38:247-251.
doi: 10.1016/j.jgar.2024.06.007. Epub 2024 Jun 25.

Susceptibility evaluation of novel beta-lactam/beta-lactamase inhibitor combinations against carbapenem-resistant Klebsiella pneumoniae from bloodstream infections in hospitalized patients in Brazil

Camila Mörschbächer Wilhelm  1 , Laura Czerkster Antochevis  2 , Cibele Massotti Magagnin  2 , Beatriz Arns  3 , Tarsila Vieceli  3 , Dariane Castro Pereira  4 , Larissa Lutz  4 , Ândrea Celestino de Souza  5 , Jéssica Nesello Dos Santos  2 , Rafaela Ramalho Guerra  2 , Gregory S Medeiros  6 , Lucas Santoro  7 , Diego R Falci  8 , Maria Helena Rigatto  9 , Afonso Luís Barth  2 , Andreza Francisco Martins  2 , Alexandre Prehn Zavascki  9
Affiliations
Free article

Susceptibility evaluation of novel beta-lactam/beta-lactamase inhibitor combinations against carbapenem-resistant Klebsiella pneumoniae from bloodstream infections in hospitalized patients in Brazil

Camila Mörschbächer Wilhelm et al. J Glob Antimicrob Resist. 2024 Sep.
Free article

Abstract

Introduction: Novel beta-lactam/beta-lactamase inhibitor (BIBLI) combinations are commercially available and have been used for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Continuous surveillance of susceptibility profiles and resistance mechanism identification are necessary to monitor the evolution of resistance within these agents.

Objective: The purpose of this study was to evaluate the susceptibility rates of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in CRKP isolated from patients with bloodstream infections who underwent screening for a randomized clinical trial in Brazil.

Methods: Minimum inhibitory concentrations (MICs) were determined for meropenem, ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam using the gradient diffusion strip method. Carbapenemase genes were detected by multiplex real-time polymerase chain reaction. Klebsiella pneumoniae carbapenemase (KPC)-producing isolates showing resistance to any BLBLI and New Delhi Metallo-beta-lactamase (NDM)-producing isolates with susceptibility to any BLBLI isolates were further submitted for whole-genome sequencing.

Results: From a total of 69 CRKP isolates, 39 were positive for blaKPC, 19 for blaNDM and 11 for blaKPC and blaNDM. KPC-producing isolates demonstrated susceptibility rates above 94 % for all BLBLIs. Two isolates with resistance to meropenem/vaborbactam demonstrated a Gly and Asp duplication at the porin OmpK36 as well as a truncated OmpK35. All NDM-producing isolates, including KPC and NDM coproducers, demonstrated susceptibility rates to ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam of 0 %, 9.1-21.1 % and 9.1-26.3 %, respectively. Five NDM-producing isolates that presented susceptibility to BLBLIs also had porin alterations CONCLUSIONS: This study showed that, although high susceptibility rates to BLBLIs were found, KPC-2 isolates were able to demonstrate resistance probably as a result of porin mutations. Additionally, NDM-1 isolates showed susceptibility to BLBLIs in vitro.

Keywords: Beta-lactamase inhibitors; Carbapenemases; Ceftazidime/avibactam; Imipenem/relebactam; Klebsiella pneumoniae; Meropenem/vaborbactam.

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Conflict of interest statement

Competing interests A.P.Z. is a research fellow of the National Council for Scientific and Technological Development (CNPq/Brazil). The authors have no relevant financial or non-financial interests to disclose.

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