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Development and Assessment of Intracellular Infection Models for Staphylococcus aureus
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Development and Assessment of Intracellular Infection Models for Staphylococcus aureus

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Acrylic microparticles increase daptomycin intracellular and in vivo anti-biofilm activity against Staphylococcus

Anne-Kathrin Woischnig1, Lidia M Gonçalves2, Maxime Ferreira3

  • 1Laboratory of Infection Biology, Department of Biomedicine, University and University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland.

International Journal of Pharmaceutics
|August 29, 2018
PubMed

Insights

Daptomycin microparticles effectively target intracellular Staphylococcus aureus and eradicate implant-associated biofilm infections, offering a promising new treatment for staphylococcal infections.

Area of Science:

  • Infectious Diseases
  • Biomaterials Science
  • Pharmacology

Background:

  • Daptomycin (DAP) shows limited efficacy against Staphylococcus aureus, particularly in biofilm and intracellular infections.
  • Current treatments struggle to eradicate staphylococcal implant-associated infections.

Purpose of the Study:

  • To evaluate the efficacy of daptomycin encapsulated in poly(methyl methacrylate)-Eudragit microparticles (DAP-MPs) against intracellular and biofilm Staphylococcus aureus.
  • To compare the therapeutic advantage of DAP-MPs versus free daptomycin in vivo.

Main Methods:

  • Antimicrobial effect of DAP-MPs on intracellular S. aureus in human osteoblasts using fluorescence in situ hybridization (FISH).
  • In vivo evaluation in a murine model of implant-associated biofilm infection using tissue cage fluid analysis.

Main Results:

  • DAP-MPs reduced intracellular S. aureus by 73% compared to blank microparticles.
  • DAP-MPs achieved clearance of planktonic MRSA and >3 log10 reduction in adherent MRSA, curing 60% of infections.
  • Prolonged higher daptomycin concentration in tissue cage fluid was observed with DAP-MPs.

Conclusions:

  • Daptomycin microparticles demonstrate significant intracellular and in vivo anti-biofilm efficacy against staphylococcal infections.
  • DAP-MPs represent a novel and effective strategy for treating challenging staphylococcal implant-associated infections.
Keywords:
MicroparticlesMouse implant-associated biofilm infection modelOrthopedic associated-infectionOsteoblastPMMA-Eudragit

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