Mechanism of therapeutic effectiveness of cefixime against typhoid fever

Y Matsumoto1, A Ikemoto, Y Wakai

  • 1Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. yoshimi_matsumoto@po.fujisawa.co.jp

Insights

Cefixime effectively inhibits intracellular Salmonella growth within mammalian cells, challenging the notion that beta-lactams are ineffective against intracellular bacteria. This study demonstrates cefixime

Area of Science:

  • Pharmacology
  • Microbiology
  • Cell Biology

Background:

  • Beta-lactam antibiotics are generally considered ineffective against intracellular bacteria due to poor cell penetration.
  • Cefixime has demonstrated clinical efficacy against typhoid fever, suggesting intracellular activity.
  • The mechanism of cefixime's effectiveness against intracellular Salmonella enterica serovar Typhi remains unclear.

Purpose of the Study:

  • To investigate the probable mechanism of cefixime's therapeutic effectiveness against intracellular Salmonella.
  • To evaluate cefixime's ability to penetrate mammalian cells and inhibit intracellular bacterial growth.

Main Methods:

  • Utilized Salmonella enterica serovar Typhimurium in a cellular infection model with THP-1 cells.
  • Employed microscopy and electron microscopy to observe bacterial morphology and growth within cells.
  • Quantified intracellular cefixime concentrations and assessed its presence in serum over time.

Main Results:

  • Cefixime successfully inhibited the growth of Salmonella Typhimurium within THP-1 cells.
  • Microscopic analysis revealed bacterial elongation and morphological changes inside cells.
  • Intracellular cefixime concentration reached 46-48% of extracellular levels, with sustained therapeutic levels in serum.

Conclusions:

  • Cefixime can effectively penetrate mammalian cells and inhibit intracellular bacterial growth.
  • The findings support cefixime's utility against intracellular Salmonella infections, including typhoid fever.
  • Bacterial sensitivity to cefixime is crucial for its intracellular efficacy.

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