Characterization of Pseudomonas aeruginosa with discrepant carbapenem susceptibility profile

Agila K Pragasam1, M Raghanivedha2, Shalini Anandan3

  • 1Department of Clinical Microbiology, Christian Medical College, Vellore, 632004, India. akilaprakasam.90@gmail.com.

Insights

Rare carbapenem resistance in Pseudomonas aeruginosa stems from intrinsic mechanisms, not carbapenemases. Mutations in the oprD gene cause imipenem resistance, while mexAB efflux pump overexpression leads to meropenem resistance.

Area of Science:

  • Clinical microbiology
  • Molecular biology
  • Antimicrobial resistance

Background:

  • Pseudomonas aeruginosa is a common cause of hospital-acquired infections, often exhibiting multidrug resistance.
  • Carbapenems are last-resort antibiotics, but resistance limits their effectiveness.
  • Intrinsic resistance mechanisms, rather than carbapenemases, are key to carbapenem resistance in P. aeruginosa.

Purpose of the Study:

  • Investigate the mechanisms behind rare carbapenem-resistant phenotypes in P. aeruginosa.
  • Characterize imipenem-resistant but meropenem-susceptible (IRMS) and meropenem-resistant but imipenem-susceptible (MRIS) phenotypes.
  • Identify the genetic and molecular basis of these unusual resistance patterns.

Main Methods:

  • Phenotypic analysis of bacterial isolates.
  • Molecular techniques to identify genetic mutations and gene expression levels.
  • Analysis of outer membrane permeability and efflux pump activity.

Main Results:

  • IRMS phenotype is primarily caused by mutations in the oprD gene.
  • MRIS phenotype is associated with the overexpression of the mexAB efflux pump.
  • Both phenotypes are linked to intrinsic/chromosomal resistance mechanisms driven by antibiotic selection pressure.

Conclusions:

  • Rare carbapenem resistance phenotypes in P. aeruginosa are mediated by intrinsic chromosomal mechanisms.
  • Mutations in oprD and mexAB efflux pump overexpression are key determinants of IRMS and MRIS phenotypes, respectively.
  • Understanding these mechanisms is crucial for managing P. aeruginosa infections and combating antimicrobial resistance.

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