Editor’s Note: Carbapenem-resistant Enterobacteriaceae (CRE) has emerged as a significant global public health threat. In recent years, there has been increasing attention on ertapenem monotherapy-resistant CRE strains, making it a hot topic in the field. At the 34th European Congress of Clinical Microbiology and Infectious Diseases (ESCMID Global 2024), a study (abstract number: P1469) by Professor Yunsong Yu‘s team at Zhejiang Provincial People’s Hospital reported on the molecular epidemiological characteristics of ertapenem monotherapy-resistant CRE. The study found that strains producing carbapenemase can still grow in high concentrations of meropenem, suggesting that monotherapy treatment may fail.
Phenotypic and Genotypic Characteristics of Ertapenem Monotherapy-Resistant Carbapenemase-Producing Enterobacteriaceae (CRE) (Abstract number: P1469)
Background
Carbapenem-resistant Enterobacteriaceae (CRE) represent a significant global public health threat. In recent years, there has been increasing reporting on strains resistant to monotherapy with ertapenem (ETP), yet the optimal treatment regimen remains uncertain. This study aims to explore the molecular epidemiological characteristics of ETP-monotherapy-resistant CRE strains, particularly focusing on carbapenemase-producing CRE (CP-CRE), to provide insights for rational antimicrobial therapy in clinical infections.
Methods
ETP-monotherapy-resistant strains were randomly matched in a 1:1 ratio with contemporaneous strains resistant to meropenem and/or imipenem (MEM/IPM), based on species or species complex type. The characteristics of ETP-monotherapy-resistant strains were elucidated using antimicrobial susceptibility testing, whole-genome sequencing, modified carbapenem inactivation method (mCIM), and reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Results
A total of 1,354 CRE strains were collected, with 18.8% of strains resistant to monotherapy with ETP. The ETP MIC distribution curve showed lower MIC values in the ETP-monotherapy-resistant group, with 76% (193/254) of strains having MIC <16 mg/L. Compared to MEM/IPM-resistant strains, ETP-monotherapy-resistant strains exhibited differences in susceptibility to β-lactams, β-lactamase inhibitor combinations, and levofloxacin.
The presence of carbapenemase genes may be a key factor contributing to the phenotypic differences in carbapenem resistance between the two groups (P < 0.001, Figure 2A).
Additionally, compared to the MEM/IPM-resistant group, the limited CP-CRE strains in the ETP-monotherapy-resistant group exhibited significantly reduced rates of extended-spectrum β-lactamase (ESBLs) gene carriage, porin mutation rates, and carbapenemase gene expression levels (Figures 3A-C). It is noteworthy that spot tests combined with semi-quantitative mCIM results suggested that ETP-monotherapy-resistant isolates producing carbapenemases could grow in environments with meropenem concentrations eight times higher than their corresponding MIC values, accompanied by rapid enhancement of carbapenem hydrolysis capability (Figures 3D-E), indicating potential clinical and/or microbiological failure during monotherapy with meropenem treatment.
Conclusion
Ertapenem monotherapy-resistant CRE strains are relatively common and exhibit phenotypic and genotypic characteristics distinct from MEM/IPM-resistant strains. Caution should be exercised when using meropenem monotherapy to treat infections caused by ETP-monotherapy-resistant CRE, and priority should be given to detecting carbapenemases.
References:
[1] Wang Y, Hu H, Shi Q, et al. Prevalence and characteristics of ertapenem-mono-resistant isolates among carbapenem-resistant Enterobacterales in China. Emerg Microbes Infect. 2024;13(1):2332658. doi:10.1080/22221751.2024.2332658
[2] Y. Wang, H. Hu, Q. Shi, et al. Phenotypic and genotypic characterization of ertapenem-mono-resistant carbapenem-resistant Enterobacterales. ESCMID Global 2024; Poster P1469.
Professor of Infectious Diseases, Chief Physician
Vice President of Zhejiang Provincial People’s Hospital
Distinguished Physician of Zhejiang University
Leading Talent of Health Commission of Zhejiang Provincial
– Director of the Infection Diseases Specialty Committee of the China Medical Education Association
– Vice Director of the Bacterial Infection and Antimicrobial Resistance Prevention and Control Specialty Committee of the Chinese Medical Association
– Director of the Bacterial Infection and Resistance Prevention and Control Specialty Committee of the Zhejiang Medical Association
– Vice Director of the Antimicrobial Rational Use and Resistance Evaluation Specialty Committee of the National Health Commission
– Director of the Zhejiang Provincial Key Laboratory of Microbial Technology and Bioinformatics
– Executive Committee Member of the Hospital Infection Control Committee of the Chinese Preventive Medicine Association
– Executive Committee Member of the Infectious Diseases Branch of the Chinese Medical Association
– Director of the Hospital Infection Control Specialty Committee of the Zhejiang Provincial Preventive Medicine Association
– Vice Director of the Infectious Diseases Specialty Committee of the Zhejiang Medical Association
– Published 145 SCI-indexed papers as first author and corresponding author
– Principal Investigator of 7 National Natural Science Foundation projects (including 2 key projects)
Currently pursuing a Ph.D. at the Zhejiang University School of Medicine
Engaged primarily in research related to antibiotic resistance and evolutionary mechanisms of Enterobacteriaceae, with 2 SCI-indexed papers published as the first author.
