Editor's Note: Carbapenem-resistant Enterobacterales (CRE) have become a significant global public health threat. In recent years, ertapenem-monotherapy resistant CRE has increasingly become a focal point of interest. At the 34th European Congress of Clinical Microbiology and Infectious Diseases (ESCMID Global 2024), a study from Professor Yunsong Yu 's team at Zhejiang Provincial People's Hospital (Abstract No.: P1469) reported on the molecular epidemiological characteristics of ertapenem-monotherapy resistant CRE. The study found that carbapenemase-producing strains can still grow in high concentrations of meropenem environments, suggesting that monotherapy may fail.Phenotypic and Genotypic Characteristics of Ertapenem-Monotherapy Resistant Carbapenem-Resistant Enterobacterales (Abstract No.: P1469)
Background:
Carbapenem-resistant Enterobacterales (CRE) are one of the major global public health threats. In recent years, reports of ertapenem (ETP) monotherapy resistant CRE strains have been increasing, yet the optimal treatment strategy remains uncertain. The main objective of this study was to explore the molecular epidemiological characteristics of ETP-monotherapy resistant CRE strains and further reveal the characteristics of carbapenemase-producing CRE (CP-CRE) strains, aiming to provide a basis for rational antimicrobial use in clinical infections.
Methods:
ETP-monotherapy resistant strains were randomly matched 1:1 with strains resistant to meropenem and/or imipenem (MEM/IPM) isolated during the same period, based on species or species complex type. The characteristics of ETP-monotherapy resistant strains were revealed through antimicrobial susceptibility testing, whole-genome sequencing, modified carbapenem inactivation method (mCIM), and reverse transcription quantitative PCR (RT-qPCR).
Results:
A total of 1,354 CRE strains were collected, of which 18.8% were resistant to ETP-monotherapy. The MIC distribution curve for the ETP-monotherapy resistant group showed lower MIC values, with 76% (193/254) of the strains having an MIC < 16 mg/L (Table 1). Compared to MEM/IPM resistant strains, the ETP-monotherapy resistant strains showed increased susceptibility to β-lactams, β-lactamase inhibitor combinations, levofloxacin, fosfomycin, amikacin, and polymyxin (P < 0.05).
Phylogenetic analysis revealed high genetic diversity among the ETP-monotherapy resistant strains. The presence of carbapenemase genes was a key factor in the phenotypic differences in carbapenem resistance between the two groups (P < 0.001).
Furthermore, compared to the MEM/IPM resistant group, the limited CP-CRE strains in the ETP-monotherapy resistant group had significantly lower rates of extended-spectrum β-lactamase (ESBLs) gene carriage, porin mutation rates, and carbapenemase gene expression levels (Figure 3A-C). Notably, spot assays combined with semi-quantitative mCIM tests suggested that carbapenemase-producing ETP-monotherapy resistant isolates can grow in environments with meropenem concentrations 8 times higher than their respective MIC values, accompanied by rapidly enhanced carbapenem hydrolysis capability, suggesting the potential for clinical and/or microbiological failure during meropenem monotherapy treatment.
Conclusion:
ETP-monotherapy resistant CRE strains are relatively common and exhibit phenotypic and genotypic characteristics different from those of MEM/IPM resistant strains. Clinicians should use caution when treating ETP-monotherapy resistant CRE infections with meropenem monotherapy and prioritize testing for carbapenemase.
