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Bacteriophages in Different Medicinal Forms

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Different Medicinal Forms of Bacteriophages for Treatment and Prevention of Bacterial Infections Induced by the Genera of Staphylococcus and Streptococcus

Tech Area / Field

  • MED-OTH/Other/Medicine
  • BIO-MIB/Microbiology/Biotechnology

Status
3 Approved without Funding

Registration date
31.10.2001

Leading Institute
Georgian Academy of Sciences / Institute of Bacteriophage, Microbiology and Virology, Georgia, Tbilisi

Collaborators

  • University of Maryland / School of Medicine / Department of Epidemiology and Preventive Medicine, USA, MD, Baltimore

Project summary

Notwithstanding the obvious successes achieved in treatment and prevention of bacterial diseases, in the meantime the purulent and septic infections still maintain a leading role in the human infectious pathologies. Universal and uncontrollable implementation of the antibiotics of wide spectrum of action, against bacterial diseases, resulted in wide distribution of the multiresistant bacterial strains; Etiological structure of purulent and intestinal infections has changed dramatically, which increased significantly the role of conditionally-pathological bacteria. The past decade has seen the increasing emergence of pathogenic bacteria which are resistant to most, if not all, currently available antimicrobial agents. This has become a critical problem in modern medicine, particularly with the concomitant increase in immunosuppressed patients (including patients undergoing organ transplantation, cancer chemotherapy, or persons infected with HIV). Prior to the discovery and widespread use of antibiotics, it had been suggested that bacterial infections could be treated by administration of bacteriophages (viruses which kill bacteria). While these early studies with bacteriophages were not rigorously pursued in the West, phages continued to be utilized in the former Soviet Union and Eastern Europe, with the activities centered at the Eliava Institute of Bacteriophage, Microbiology, and Virology of the Georgian Academy of Sciences, Tbilisi, Georgia (one of the former Soviet Union Republics). Out of the microorganisms representing most important pathogens in human a special role belongs to the gram-positive cocci of the Firmicutus pision, Staphylococcus and Streptococcus genera.
The most important pathogens inducing a vast number of diseases – those from the upper respiratory tract and focal abscesses to the fatal sepsis – are the staphylococci. Such a multiple pathogeneicity is due to the ability of staphylococcal cells to rapidly acquire a resistance against the novel antibiotics. The dominant position in the human pathologies hold hemolytic streptococci of the serovar A, which induce skin infections, scarlet fever, toxic tonsillo-pharyngitis, as well as newly recorded clinical forms – syndrome of clinical shock, necrotic myositis and fascitis, and primary peritonitis. Recently a significant spread of streptococcal infections has been registered, which are characterized with bursting of disease and its heavy course. Because of decreasing efficiency of the antibiotics, allergic responses of the organism to their administration, and rise of the bacterial strains resistant against the antibacterial substances, all these make search and implementation of novel, highly active and still harmless, antibacterial preparations most pressing problem. Just to such preparations belong the medicinal-prophylactic bacteriophages, which posses safe, stable, and highly specific mode of action Therapeutic application of the bacteriophages on the background of spreading of the multiresistant microorganisms should be viewed as the alternative for antibiotics and sulfanilamides.
The phage-therapy has been successfully and efficiently implemented in the Former Soviet Union countries. For many years the Tbilisi Institute of Bacteriophagy, Microbiology and Virology was a leading center for investigation of especially dangerous bacterial organisms. At the same time, Institute worked in isolation and selection of active bacterial viruses against the pathogenic microorganisms, and in creation of therapeutic phage preparations. The preparations of specific phages have been successfully used in burn-, septic-, gastroenterological-, pediatric centers and surgical departments of the clinics, against the primary and nosocomial infections.
Absence of the bacteriophage action efficacy in certain cases should be due to insufficient diagnostics and incorrect choice of the method for implementation of a specific phage. Therefore, during creation of the new preparations, one must not be restricted by the earlier applied means, but rather should implement novel methods in both investigation of the phages and new technological schemes of their production, and new medicinal forms must be constructed. Meanwhile, different medicinal forms will require different demands to methodological approaches and production. In mass application of the bacteriophages in any medicinal form one of the major factors is obtaining the high quality phage preparations, possessing a wide spectrum of action.
In this respect important factors for implementation of the phages with positive medicinal effect are timely and precise diagnostic of bacterial infection, isolation of bacterial strains, selection of specific phage preparation with wide spectrum action, or creation of a preparation for each inpidual case; Isolation of the atphylococcal, streptococcal, and escherichial strains from the patients from different regions of Georgia and Tbilisi, covering various clinics and independent contingent.
The goal of this Project is selection of the active phages against staphylococcal, streptococcal and escherichial microorganisms, and creation of novel medicinal-preventive phages, in different combinations and in different medicinal forms – as routinely known (liquid), so in the new forms (powder, ointment, suppository).
- To identify lytic bacteriophages with lytic activity against multidrug-resistant Staphylococcus and Steptococcus (including vancomycin-resistant mutants);
- To develop a cocktail of anti- Stapilococcus and Steptococcus phages having optimal lytic activity against genetically perse Stapilococcus and Steptococcus strain population, and
- To test the in vivo Stapilococcus and Steptococcus efficacy of the phage cocktail to prevent and/or treat
infections caused by multidrug-resistant Stapilococcus and Steptococcus strains.
- The phages of the Institute Collection, as well as the freshly isolated phages from the environment will be implemented in the screening procedures.
- It is considered to study a number of taxonomic properties of the new phages according to the scheme proposed by the World Committee for Classification of Viruses.
All investigations concerned with bacterial strains and phages will be used in creation of medicinal mono- and polycompetent phage preparations, in various medicinal forms.


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