Spiramycin: The past and future of an antibiotic with pleiotropic effects in the therapy of community-acquired infections

The aim of the work was to search and analyze works on pharmacokinetic (PK) and pharmacodynamic (PD) parameters of spiramycin, allowing to evaluate the potential of this macrolide in the therapy of community-acquired infections. Materials and & mcy;ethods. The abstract databases of PubMed, Google Scholar, EMBASE, the ResearchGate scientific information network and elibrary.ru were used to search for the materials. The following key queries were used in the work: "pharmacokinetics of spiramycin", "pharmacokinetic parameters of spiramycin", "pharmacodynamics of spiramycin", "mechanism of action of spiramycin", "targets for spiramycin", "pharmacodynamic effects of spiramycin". The search depth-69 years (1955-2024), the total number of publications included in the literature review in the areas of "pharmacokinetics" and "pharmacodynamics" was 72. The total number of the sources used in the article amounted is 152. Results. With the spread of the antibiotic resistance (AR) among the pathogens of both nosocomial and community-acquired infections, it is important for physician to search for strategies to preserve the possibility of using first-line antibacterial drugs (ABDs) in patients with infectious diseases. Spiramycin has been characterized by a minimal consumption by the population in the last decades, thus, it has a potential for the therapy of infectious diseases. The analysis of the PK spiramycin parameters indicates the ability to form effective concentrations in various tissues and organs, as well as a minimal risk of drug interactions that can alter the therapeutic response. The evaluation of its antibacterial activity in vitro and in vivo yields different results, indicating the ability of the drug to exhibit significantly greater efficacy in vivo. This paradox may be based on pleiotropic effects of spiramycin involving both host cells (immunomodulatory and anti-inflammatory effects, the ability to favorably affect the tissue regeneration, the antitumor activity, the inhibition of adipogenesis) and pathogen targets (the ability to reduce the virulence of P. aerugenosa, the antiviral effect, the reduction of the adhesion ability of cocci). Conclusion. The PK and PD parameters and the properties of spiramycin along with the results of the published clinical studies evaluating its efficacy indicate that, despite its lower in vitro activity, the presence of additional pleiotropic effects may be the key to its superiority over the traditional macrolides in in vivo methods.