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Objectives <p>Drug-resistant <i>Enterobacterales</i> carrying carbapenem-resistant genes cause severe infections in clinical settings worldwide. Among these, the New Dehli Metallo-β-lactamase (<i>bla</i><sub>NDM</sub>) gene is significantly prevalent and associated with high morbidity. This study was designed to investigate the susceptibility profiling of <i>Carbapenem-Resistant-Enterobacterales</i> (CRE), prevalence of <i>bla</i><sub>NDM</sub> and its variants, and associated risk factors.</p> Methods <p>CRE isolates from a tertiary care hospital, in Islamabad, Pakistan, were identified and the susceptibility testing was performed using disc diffusion method. MICs were determined for imipenem, tigecycline, and colistin through E-strips and microbroth dilution method respectively. For molecular characterization and typing of the <i>bla</i><sub>NDM</sub> gene, PCR products were sequenced, and the phylogenetic analysis was performed using MEGA ver 6.0 software.</p> Results <p>Among 5,134 clinical samples, 42.13% (<i>n</i> = 2,163) yielded pathogens including 42.58% (<i>n</i> = 921) <i>Enterobacterales</i>. On further screening, 39.52% (<i>n</i> = 364) of <i>Enterobacterales</i> were identified as CRE. The <i>bla</i><sub>NDM</sub> gene was detected in 75.27% (<i>n</i> = 274) in CRE isolates, comprising <i>bla</i><sub>NDM−1</sub> (44%), <i>bla</i><sub>NDM−5</sub> (53%), and <i>bla</i><sub>NDM−7</sub> (3%) variants. Tigecycline (86.7%) and colistin (100%) were most effective antimicrobial agents with MICs ranging from 0.064 to 8 and 0.125–1&#xa0;µg/ml respectively. <i>bla</i><sub>NDM−1</sub>-harboring bacteria exhibited high antimicrobial resistance compared to <i>bla</i><sub>NDM−5</sub> and <i>bla</i><sub>NDM−7</sub>. Cefiderocol was 75.6% and ceftazidime/avibactam with aztreonam was 97.08% effective against <i>bla</i><sub>NDM</sub>-harboring bacteria. The phylogenetic analysis indicated that <i>bla</i><sub>NDM</sub> variants showed close genetic relationships and homology to the previously described sequences in GenBank databases having diverse connection with worldwide sequences.</p> Conclusion <p>The high prevalence of <i>bla</i><sub>NDM</sub> in our study has of great concern for clinical practice and public health. Clinicians are left with few therapeutic options. However, ceftazidime/avibactam with aztreonam may show therapeutic success. Continuous surveillance is crucial to monitorgenetic variations of continuously evolving <i>bla</i><sub>NDM</sub> gene, which is essential for effective clinical management.</p>

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Prevalence of New Delhi Metallo-β-lactamase (blaNDM) gene in a selected population of drug-resistant clinical isolates

  • 期刊论文

  • 发表日期：

    2025年4月15日

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  • Muhammad Shafiq,
  • Aftab Ahmad,
  • Kunza Latif,
  • Muhammad Saeed,
  • Iftikhar Ahmed,
  • Muhammad Zeeshan Hyder

摘要

Objectives

Drug-resistant Enterobacterales carrying carbapenem-resistant genes cause severe infections in clinical settings worldwide. Among these, the New Dehli Metallo-β-lactamase (blaNDM) gene is significantly prevalent and associated with high morbidity. This study was designed to investigate the susceptibility profiling of Carbapenem-Resistant-Enterobacterales (CRE), prevalence of blaNDM and its variants, and associated risk factors.

Methods

CRE isolates from a tertiary care hospital, in Islamabad, Pakistan, were identified and the susceptibility testing was performed using disc diffusion method. MICs were determined for imipenem, tigecycline, and colistin through E-strips and microbroth dilution method respectively. For molecular characterization and typing of the blaNDM gene, PCR products were sequenced, and the phylogenetic analysis was performed using MEGA ver 6.0 software.

Results

Among 5,134 clinical samples, 42.13% (n = 2,163) yielded pathogens including 42.58% (n = 921) Enterobacterales. On further screening, 39.52% (n = 364) of Enterobacterales were identified as CRE. The blaNDM gene was detected in 75.27% (n = 274) in CRE isolates, comprising blaNDM−1 (44%), blaNDM−5 (53%), and blaNDM−7 (3%) variants. Tigecycline (86.7%) and colistin (100%) were most effective antimicrobial agents with MICs ranging from 0.064 to 8 and 0.125–1 µg/ml respectively. blaNDM−1-harboring bacteria exhibited high antimicrobial resistance compared to blaNDM−5 and blaNDM−7. Cefiderocol was 75.6% and ceftazidime/avibactam with aztreonam was 97.08% effective against blaNDM-harboring bacteria. The phylogenetic analysis indicated that blaNDM variants showed close genetic relationships and homology to the previously described sequences in GenBank databases having diverse connection with worldwide sequences.

Conclusion

The high prevalence of blaNDM in our study has of great concern for clinical practice and public health. Clinicians are left with few therapeutic options. However, ceftazidime/avibactam with aztreonam may show therapeutic success. Continuous surveillance is crucial to monitorgenetic variations of continuously evolving blaNDM gene, which is essential for effective clinical management.