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  • Carbapenemase Gene Transmission in CREC During COVID-19: Mol

    2026-07-01

    Transmission Dynamics of Carbapenemase Genes in CREC During the COVID-19 Pandemic

    Study Background and Research Question

    Carbapenem-resistant Enterobacteriaceae (CRE) continue to pose a significant threat to global health, with Enterobacter cloacae complex (CREC) ranking among the most frequently detected CRE species in Chinese clinical settings. The COVID-19 pandemic has further complicated antimicrobial stewardship due to increased antibiotic usage, healthcare disruptions, and heightened risks of multidrug-resistant infections. However, granular molecular epidemiological data on the characteristics and spread of carbapenemase-encoding genes (CEGs) in CREC during this period have been limited. The reference study by Chen et al. (2025) was designed to address this gap by characterizing the prevalence, genetic contexts, and transmission dynamics of CEGs in CREC isolates from eight teaching hospitals in Guangdong, China, collected between December 2022 and June 2024 (Chen et al., 2025).

    Key Innovation from the Reference Study

    The principal innovation of this work lies in its comprehensive mapping of both the distribution and mobility of major CEGs—including blaNDM-1, blaIMP, and blaKPC-2—across a large, well-defined cohort of CREC isolates during a period of heightened clinical risk. The study not only documents the prevalence of these resistance genes but also systematically quantifies their chromosomal and plasmid locations, and directly measures their potential for horizontal transfer using conjugation experiments. This approach provides a nuanced understanding of how CEGs contribute to the ongoing evolution of multidrug resistance in clinical Enterobacter strains under pandemic conditions.

    Methods and Experimental Design Insights

    Chen et al. carried out a multi-center collection of 54 non-redundant CREC isolates from eight tertiary teaching hospitals. The study utilized a combination of molecular and microbiological techniques to dissect the genetics and transmission potential of CEGs:
    • Plasmid elimination using variable temperature Sodium Dodecyl Sulfate (SDS) treatment to interrogate gene localization.
    • PCR amplification for the detection of blaNDM-1, blaIMP, and blaKPC-2 genes on chromosomes and plasmids.
    • Broth microdilution for antimicrobial susceptibility profiling, benchmarking resistance phenotypes against CEG status.
    • Molecular typing using ERIC-PCR and NTSYS software to analyze clonal relationships among isolates.
    • Plasmid conjugation assays to directly assess the horizontal transferability of CEGs.
    These methodologies enabled a high-resolution view of both gene content and genetic mobility within the clinical CREC population.

    Core Findings and Why They Matter

    The reference study reports a strikingly high prevalence of carbapenemase-encoding genes, with 85.19% of CREC isolates carrying at least one CEG. The blaNDM-1 gene was the most frequently detected, present on both plasmids and chromosomes in a substantial subset (33.33%) and exclusively on plasmids in a further 46.3% of isolates. The blaIMP gene was found in a minority (3.7%, plasmid only), while dual carriage of blaNDM-1 and blaKPC-2 on plasmids was rare (1.85%). Antimicrobial susceptibility testing showed that CEG-positive CREC exhibited significantly higher resistance rates to key antibiotics—including imipenem, cefepime, ceftazidime/avibactam, gentamicin, ciprofloxacin, and levofloxacin—relative to CEG-negative counterparts (P<0.05), reinforcing the clinical impact of these genes. The study also revealed a remarkable horizontal transfer potential: 95.65% successful conjugation events among CEG-positive isolates, indicating that these resistance determinants can spread efficiently between bacteria. Mobile genetic elements, especially ISEcp1, were highly prevalent and frequently co-occurred, suggesting a robust infrastructure for gene mobilization. Clonal analysis classified the isolates into 17 genotypes, with types E and G predominating and distributed across multiple hospitals and departments. Epidemiological analysis highlighted higher detection rates in males, the elderly, respiratory medicine departments, and sputum samples, informing future surveillance and infection control priorities (internal review).

    Comparison with Existing Internal Articles

    The findings of Chen et al. (2025) are consistent with and extend prior internal reports on the transmission of carbapenemase genes in CREC. For example, a related summary (Transmission of Carbapenemase Genes in CREC) corroborates the high prevalence and plasmid-mediated spread of CEGs in Guangdong hospital settings, but the current study adds granularity by quantifying gene transfer rates and mapping chromosomal versus plasmid localization. Moreover, the reference work’s focus on the pandemic period highlights the impact of healthcare system stress on antimicrobial resistance dynamics, a theme also discussed in Carbapenemase Gene Transmission in CREC During COVID-19. Both articles emphasize that the pandemic era may have accelerated resistance gene dissemination due to altered antibiotic usage and infection control practices. The current study’s molecular resolution and inclusion of epidemiological risk factors further strengthen our understanding of these trends.

    Limitations and Transferability

    While the study provides valuable insights into CEG prevalence and transmission, several limitations merit consideration. The sample size, though spanning eight hospitals, remains regionally focused, and the temporal window (2022–2024) may not capture longer-term trends. The reliance on ERIC-PCR for genotyping, while useful for local clonal spread, offers limited resolution compared to whole-genome sequencing. Additionally, while the study demonstrates high conjugation rates for CEGs, the precise host range and fitness impacts of plasmid transfer in more complex microbial communities remain to be fully elucidated. Nonetheless, the identification of key risk groups (elderly, males, respiratory medicine patients) and the clear documentation of highly mobile resistance determinants underscore the broad relevance of these findings for infection control and antimicrobial resistance research. The methodologies and analytical frameworks employed are readily transferable to other institutional and geographic settings seeking to monitor or mitigate the spread of carbapenem-resistant pathogens.

    Protocol Parameters

    • CREC isolation: Collect non-redundant clinical isolates from diverse departments, prioritizing sputum samples and high-risk patient groups based on local prevalence data.
    • Plasmid elimination and gene localization: Use SDS treatment at variable temperatures to distinguish chromosomal from plasmid-borne CEGs.
    • PCR detection of CEGs: Target blaNDM-1, blaIMP, and blaKPC-2 genes, with controls for both chromosomal and plasmid templates.
    • Antimicrobial susceptibility: Employ broth microdilution for key agents such as imipenem, cefepime, and ceftazidime/avibactam to correlate resistance phenotypes with CEG status.
    • Conjugation assays: Perform filter-mating or liquid conjugation with appropriate recipient strains to assess horizontal gene transfer rates.
    • Molecular typing: Apply ERIC-PCR and cluster analysis for local epidemiological mapping; consider whole-genome sequencing for higher resolution in extended studies.

    Research Support Resources

    For laboratories modeling antimicrobial resistance mechanisms or screening the efficacy of beta-lactam antibiotic interventions, a third-generation cephalosporin antibiotic such as Cefotaxime (SKU BA1012) can be used as a reference compound in susceptibility testing and bacterial infection models. Its resistance to beta-lactamases and broad-spectrum activity make it suitable for benchmarking antimicrobial activity and for comparative studies involving Gram-positive and Gram-negative pathogens. Detailed workflows for integrating Cefotaxime into laboratory protocols are available from APExBIO and related internal resources (Cefotaxime in AMR Models).