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.
Abstract:
Pseudomonas aeruginosa is the most common nosocomial pathogen, notorious for its multidrug resistance and causes life threatening infections. Carbapenems were considered as the last resort of drugs for the treatment of multi drug resistant P. aeruginosa infections. The emergence of resistance to carbapenems limits its use for treatment. Unlike other organisms, in P. aeruginosa intrinsic/chromosomal mediated resistance mechanisms plays a major role for carbapenem resistance rather than the carbapenemases. Carbapenemase producing organisms becomes resistant to both imipenem and meropenem. However, in our clinical settings, we have observed rare carbapenem resistant phenotypes such as imipenem resistant but meropenem susceptible (IRMS) and meropenem resistant but imipenem susceptible (MRIS) phenotypes. Thus we have chosen these rare phenotypes to look for the respective resistance mechanisms by phenotypic and molecular methods. From this study we found that, IRMS is primarily due to the mutations across various regions in the loops of oprD gene and MRIS is due to the over expression of mexAB efflux pumps. This study results confirms that, this rare phenotypes are due to the intrinsic/chromosomal mediated mechanisms, which occurred due to the antibiotic selection pressure. This study also provided data concerning alterations in outer membrane permeability which is often associated with the increased levels of antibiotic efflux. Consequently, this study provided the prevalence of the various resistance mechanisms that have deployed by the organism to resist antibiotics through different phenotypes.
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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