[Experimental evaluation of antibiotics as immunomodulators]

Area of Science:

• Immunology and Pharmacology
• Microbiology and Infectious Diseases

Background:

• Cooperation between therapeutics and host defense system (HDS) is crucial for optimal treatment efficacy.
• Antibacterial agents (ABA) efficacy is traditionally measured by MICs, MBCs, and pharmacokinetics, but clinical data emphasize the need for HDS synergy.
• While most ABA have minimal in vivo immune effects, some exhibit immunomodulatory properties.

Purpose of the Study:

• To investigate the immunomodifying properties of antibacterial agents.
• To introduce the concept of Biological Response Modifier (BRM)-antibiotics.
• To highlight cefodizime as a parenteral cephalosporin with demonstrated immunomodulating effects.

Main Methods:

• In vitro studies assessing phagocyte antimicrobial activity.
• Ex vivo analysis in immunocompromised animals and humans to evaluate immune parameter restoration.
• In vivo infection models using both sensitive and resistant microbial species.

Main Results:

• Cefodizime, a novel parenteral cephalosporin, exhibits significant immunomodulating properties.
• Demonstrated potentiation of phagocyte antimicrobial activity in vitro.
• Restored immune parameters in immunocompromised models and showed efficacy in vivo.

Conclusions:

• Cefodizime acts as a Biological Response Modifier (BRM)-antibiotic, enhancing host defense.
• The thio-thiazolyl moiety at the C3 position of the cephem nucleus is identified as the structural basis for BRM activity.
• Further research is needed to elucidate the precise mechanisms underlying cefodizime's immunomodulatory effects.