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In vitro antimicrobial activity of liposomal meropenem against Pseudomonas aeruginosa strains

Zuzanna Drulis-Kawa1, Jerzy Gubernator, Agata Dorotkiewicz-Jach

  • 1Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148 Wroclaw, Poland. kawa@microb.uni.wroc.pl

International Journal of Pharmaceutics
|March 23, 2006
PubMed

Insights

Cationic liposomes enhanced meropenem activity against susceptible Pseudomonas aeruginosa, but liposomal formulations showed limited efficacy against resistant strains due to low permeability. Further research is needed for drug-resistant bacterial infections.

Area of Science:

  • Pharmaceutical Sciences
  • Microbiology
  • Drug Delivery

Background:

  • Meropenem is a crucial antibiotic for treating bacterial infections.
  • Liposomal drug delivery systems offer potential for enhanced antimicrobial efficacy and targeted delivery.
  • Pseudomonas aeruginosa poses a significant challenge due to its intrinsic and acquired drug resistance mechanisms, including low outer membrane permeability.

Purpose of the Study:

  • To evaluate the antibacterial activity of twelve novel lipid formulations of liposomal meropenem.
  • To compare the efficacy of different liposomal formulations against drug-susceptible and drug-resistant Pseudomonas aeruginosa strains.
  • To investigate the influence of liposome charge and composition on meropenem's activity.

Main Methods:

  • Preparation and characterization of twelve distinct liposomal meropenem formulations.
  • Determination of Minimum Inhibitory Concentrations (MICs) against six drug-susceptible and two drug-resistant Pseudomonas aeruginosa strains.
  • Assessment of liposome-bacterial membrane interactions, including fusion, for specific formulations like Fluidosomes.

Main Results:

  • Cationic liposomal meropenem formulations (PC/DOPE/SA 4:4:2 and PC/DOTAP/Chol 5:2:3) exhibited lower MICs (two to four times) than free meropenem against susceptible P. aeruginosa.
  • Anionic liposomes were less effective than cationic ones against susceptible strains.
  • None of the tested liposomal meropenem formulations demonstrated bactericidal activity against drug-resistant P. aeruginosa strains, which are characterized by low permeability.
  • Fluidosomes, despite showing membrane fusion, displayed significantly higher MICs (4-16 times) compared to free meropenem for both susceptible and resistant strains.

Conclusions:

  • Cationic liposomes show promise in enhancing meropenem's activity against susceptible P. aeruginosa by improving delivery or interaction.
  • Liposomal encapsulation does not overcome the low-permeability barrier in drug-resistant P. aeruginosa strains, limiting therapeutic potential.
  • Further development of liposomal strategies is required to effectively combat multidrug-resistant bacterial infections.

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