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<p>The emergence of <i>Serratia marcescens</i> as a significant healthcare-associated pathogen is compounded by its rising carbapenem resistance resulting in a critical global health challenge. This study is the first in Pakistan to comprehensively characterize the antimicrobial resistance patterns and molecular mechanisms of <i>S. marcescens</i> from clinical specimens. The <i>S. marcescens</i> isolates were obtained from clinical specimens collected at tertiary care hospitals in Lahore and Faisalabad, Pakistan, between October 2023 and September 2024. Isolates were identified using the Vitek-2 system and MALDI-TOF mass spectrometry. The disk diffusion assays, and broth microdilution method were used for antimicrobial susceptibility testing. The antimicrobial resistance determinants were amplified by PCR followed by sanger sequencing. The study revealed concerning resistance rates among <i>S. marcescens</i> isolates: 78% were resistant to third-generation cephalosporins, 52% to carbapenems, and 71.6% to fluoroquinolones. However, no isolates were found to be resistant to the tigecycline. The carbapenem resistance genes were distributed among carbapenem-resistant <i>S. marcescens</i> (CRSM) strains as follows: <i>bla</i><sub>OXA-48</sub> was most prevalent at 69.2%, followed by <i>bla</i><sub>KPC</sub> at 20.8%, and <i>bla</i><sub>IMP</sub> at 10% of isolates. The 16S methylase gene <i>armA</i> was found exclusively in CRSM strains, present in 73.1% (95/130) of isolates. The <i>aac</i>(6′)-Ib-cr gene variant, which confers resistance to aminoglycosides and fluoroquinolones, was found in 37.2% of CRSM isolates. The CRSM isolates co-harboring <i>bla</i><sub>OXA-48</sub>, <i>armA</i>, and aac(6′)-Ib-cr genes demonstrated a convergence of carbapenem, aminoglycoside, and fluoroquinolone resistance mechanisms which confer a multi-drug resistance phenotype in these isolates, with tigecycline remaining the sole susceptible agent. These findings expose an escalating AMR crisis in Pakistan driven by high-risk resistance gene combinations among <i>S. marcescens</i> isolates. This underscores the dire necessity for urgent nationwide interventions including rapid diagnostics, genomic surveillance of resistance mechanisms, and strict antibiotic stewardship to curb the increasing antimicrobial resistance threats and nosocomial transmission of such pathogens. </p>

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Carbapenem Resistant Serratia marcescens Harboring blaOXA-48, armA and aac(6′)-Ib-cr Genes: The First Baseline Study from Pakistan

  • 期刊论文

  • 发表日期：

    2025年6月3日

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  • Amna Kausar,
  • Muhammad Sohail,
  • Mohsin Khurshid,
  • Hafiz Ghulam Murtaza Saleem

摘要

The emergence of Serratia marcescens as a significant healthcare-associated pathogen is compounded by its rising carbapenem resistance resulting in a critical global health challenge. This study is the first in Pakistan to comprehensively characterize the antimicrobial resistance patterns and molecular mechanisms of S. marcescens from clinical specimens. The S. marcescens isolates were obtained from clinical specimens collected at tertiary care hospitals in Lahore and Faisalabad, Pakistan, between October 2023 and September 2024. Isolates were identified using the Vitek-2 system and MALDI-TOF mass spectrometry. The disk diffusion assays, and broth microdilution method were used for antimicrobial susceptibility testing. The antimicrobial resistance determinants were amplified by PCR followed by sanger sequencing. The study revealed concerning resistance rates among S. marcescens isolates: 78% were resistant to third-generation cephalosporins, 52% to carbapenems, and 71.6% to fluoroquinolones. However, no isolates were found to be resistant to the tigecycline. The carbapenem resistance genes were distributed among carbapenem-resistant S. marcescens (CRSM) strains as follows: blaOXA-48 was most prevalent at 69.2%, followed by blaKPC at 20.8%, and blaIMP at 10% of isolates. The 16S methylase gene armA was found exclusively in CRSM strains, present in 73.1% (95/130) of isolates. The aac(6′)-Ib-cr gene variant, which confers resistance to aminoglycosides and fluoroquinolones, was found in 37.2% of CRSM isolates. The CRSM isolates co-harboring blaOXA-48, armA, and aac(6′)-Ib-cr genes demonstrated a convergence of carbapenem, aminoglycoside, and fluoroquinolone resistance mechanisms which confer a multi-drug resistance phenotype in these isolates, with tigecycline remaining the sole susceptible agent. These findings expose an escalating AMR crisis in Pakistan driven by high-risk resistance gene combinations among S. marcescens isolates. This underscores the dire necessity for urgent nationwide interventions including rapid diagnostics, genomic surveillance of resistance mechanisms, and strict antibiotic stewardship to curb the increasing antimicrobial resistance threats and nosocomial transmission of such pathogens.