KPC Overexpression and Ceftazidime-Avibactam Heteroresistance in Klebsiella pneumoniae
Author Information
Author(s): Li Yitan, Chen Xiandi, Guo Yingyi, Lin Yingzhuo, Wang Xiaohu, He Guohua, Wang Mingzhen, Xu Jianbo, Song Mingdong, Tan Xixi, Zhuo Chao, Lin Zhiwei
Primary Institution: Key Laboratory of Respiratory Disease, People’s Hospital of Yangjiang, Yangjiang, China
Hypothesis
This study aimed to investigate the characteristics and mechanisms of CZA heteroresistance in CRKP isolates.
Conclusion
The study identified that overexpression of KPC contributes to CZA heteroresistance in CRKP isolates, and increasing avibactam concentration or combining it with tigecycline can effectively prevent this resistance.
Supporting Evidence
- 34 (12.4%) CZA-susceptible CRKP isolates exhibited heteroresistance to CZA.
- All heteroresistant strains belonged to KPC-2 (97.1%) or KPC-3 (2.9%).
- Imipenem-relebactam and meropenem-vaborbactam showed excellent activity against resistant subpopulations.
- Silencing bla KPC expression decreased the CZA MIC in resistant subpopulations.
- Increasing avibactam concentration significantly suppressed the formation of CZA heteroresistance.
Takeaway
Some bacteria can be resistant to a medicine even if they usually respond to it, and this study found that a specific gene makes some Klebsiella pneumoniae bacteria resistant to a treatment called ceftazidime-avibactam.
Methodology
The study collected 311 CRKP clinical strains and evaluated their resistance using broth microdilution, population analysis profiling, and molecular sequencing.
Limitations
The study may not cover all possible resistance mechanisms and focuses primarily on KPC-related heteroresistance.
Participant Demographics
Clinical strains collected from inpatients in three tertiary hospitals in Guangdong province, China.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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