In vitro activity of ceftazidime-avibactam, imipenem-relebactam, aztreonam-avibactam, and comparators toward carbapenem-resistant and hypervirulent Klebsiella pneumoniae isolates

Dan Li; Hua Yu; Xiangning Huang; Shanshan Long; Jie Zhang

doi:10.1128/spectrum.02806-23

Microbiology Spectrum (Dec 2023)

In vitro activity of ceftazidime-avibactam, imipenem-relebactam, aztreonam-avibactam, and comparators toward carbapenem-resistant and hypervirulent Klebsiella pneumoniae isolates

Dan Li,
Hua Yu,
Xiangning Huang,
Shanshan Long,
Jie Zhang

Affiliations

Dan Li: School of Medicine, University of Electronic Science and Technology of China , Chengdu, China
Hua Yu: Department of Laboratory Medicine, Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu , Sichuan, China
Xiangning Huang: Department of Laboratory Medicine, Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu , Sichuan, China
Shanshan Long: Department of Laboratory Medicine, Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu , Sichuan, China
Jie Zhang: Department of Laboratory Medicine, Sichuan Provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu , Sichuan, China

DOI: https://doi.org/10.1128/spectrum.02806-23
Journal volume & issue: Vol. 11, no. 6

Abstract

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ABSTRACT Carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) strains are increasingly reported, posing a significant threat to public health. Therefore, effective antimicrobial therapy is urgently needed. This study aimed to analyze the in vitro activity of ceftazidime-avibactam (CZA), imipenem-relebactam (IMR), and aztreonam-avibactam (AZA) toward CR-hvKP and carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates. Non-repetitive clinical CRKP and CR-hvKP strains were collected from Sichuan Provincial People’s Hospital between August 2018 and June 2022. CR-hvKP strains were screened using string tests and polymerase chain reaction (PCR). The microbroth dilution method was used to evaluate in vitro antibacterial activity of CZA, IMR, and AZA toward CRKP and CR-hvKP stains. The molecular characteristics of CRKP and CR-hvKP strains were investigated using PCR amplification. The virulence features of CR-hvKP strains were investigated using serum resistance assays and a Galleria mellonella infection model. A total of 114 CRKP and 40 CR-hvKP strains were collected. The susceptibility rates of CRKP and CR-hvKP to tigecycline, colistin, and polymyxin B exceeded 89.5%. The susceptibility rates of CRKP and CR-hvKP to CZA were 64.0% and 77.5%, respectively; the susceptibility rates to IMR were 92.5% and 71.9%, respectively; and the susceptibility rates to AZA were 89.5% and 75.0%, respectively. Multilocus sequence typing and wzi-loci sequencing identified sequence type 11 KL64 as the predominant type in CRKP and CR-hvKP strains. Carbapenemase genes were dominated by blaKPC-2 and blaNDM-1. IMR and AZA may be promising therapeutic agents for the treatment of infections caused by CRKP and CR-hvKP isolates. IMPORTANCE To our knowledge, this is the first study to report the in vitro activity of two novel antimicrobial drugs, including imipenem-relebactam (IMR) and aztreonam-avibactam (AZA), toward carbapenem-resistant and hypervirulent Klebsiella pneumoniae (CR-hvKP) strains. Our in vitro activity study revealed that only few antibacterial agents (including several novel agents) exhibit high antimicrobial activity toward carbapenem-resistant Klebsiella pneumoniae (CRKP) and CR-hvKP isolates. IMR and AZA may be promising therapeutic agents for the treatment of infections caused by CRKP and CR-hvKP isolates.

Published in Microbiology Spectrum

ISSN: 2165-0497 (Online)
Publisher: American Society for Microbiology
Country of publisher: United States
LCC subjects: Science: Microbiology
Website: https://journals.asm.org/journal/spectrum

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