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Interaction between Bacteriophages and Antibiotics

#G-1735


Study of Interactions between Antibiotics And Bacteriophages for Strains Isolated From Patients During the Treatment of Suppurative Infections

Tech Area / Field

  • MED-DIS/Disease Surveillance/Medicine

Status
3 Approved without Funding

Registration date
01.04.2009

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

Collaborators

  • Dr-George-L.-Dumont Regional Hospital, Canada, NB, Moncton\nKatholieke Universiteit Leuven / Laboratory of Gene Technology, Belgium, Leuven\nUniversity of Leicester / Department of Infection, Immunity and Inflammation, UK, Leicester\nInstitut Pasteur, France, Paris\nCentre Hospitalier Villeneuve St.G, France, Vincennes\nThe Evergreen State College, USA, MD, Washington

Project summary

The emergence of pathogenic bacteria resistant to most, if not all, currently available anti-microbial agents has become a critical problem in modern medicine, particularly because of the concomitant increase in immuno-suppressed patients. The concern that mankind is reentering the “pre-antibiotics era” has become very real, and development of alternative anti-infection modalities has become one of the highest priorities of modern medicine. Purulent infections are among the most important problems, seriously concerning both developed and developing countries because of the high rate of infection lethality and socio-economic damage. In the last 20 years, a sharp increase of inflammatory infections caused by both Gram-positive and Gram-negative bacteria has been seen, clinically expressed as purulent septic diseases. The use of a wide spectrum of antibiotics has played an important role in the struggle against infectious diseases, but at the same time the uncontrolled and sometimes needless use of antibiotics and resultant development and spreading of antibiotic-resistant strains causes great trouble. The etiological structure of infectious diseases, and particularly of hospital-acquired infections, has changed because of the natural and acquired multiple antibiotic resistance. [3,21]

Antibiotic resistance spreads fast. In 1992, 13,300 hospitalized patients in the USA were resistant to antibiotic therapy [37] and the figures are increasing every year, among both gram-positive and gram-negative bacteria. [18]. 20]..[18,35].[17,19].[38] [22].

Research has shown that resistance of these bacteria to classic treatment in humans is often a consequence of the use of certain antimicrobials in agriculture. WHO encourages countries to use all opportunities to reduce, to the extent possible, the use of antibiotics outside human medicine. This will minimize the risk of the emergence of antimicrobial resistance in bacteria, which can be transmitted to humans from animals or the environment. The overall aim is to ensure that infectious disease in humans can be controlled more efficiently. [39]

Bacteriophages have been used therapeutically for much of the last century in some parts of the world. In the early years, there were exciting successes in both prophylaxis and therapy but also discouraging failures, probably mainly due to lack of understanding and resultant use of phages that were inactive against the infection in question. With the advent of antibiotics, the therapeutic use of phage gradually fell out of favor in the U.S. and Western Europe and little subsequent research was conducted. However, bacteriophage therapy continued to be utilized in Eastern Europe [26,27,29] most notably in Poland and the former Soviet Union. The most extensive work evaluating the utility of therapeutic phages for infectious diseases was conducted here in Tbilisi, Georgia. [23,24,25,33]

Determining the frequency of occurrence of multiple resistance to clinical preparations (antibiotics, bacteriophages), and investigation of the resistance mechanisms will enable us to make important modifications in the treatment protocols and select the phages that work best in such combinations. The efficacy of phage treatment with vs. without appropriate antibiotics will then be tested in small-scale clinical trials involving two or three selected key problems. Characterization of the genomes and biology of the most effective phages (as is required before their approval for clinical administration) will provide information for classification and better understanding of them and their ecology, supporting their future application in the processes of patient treatment in cases of increased resistance to antibiotics.

All of the research workers and physicians participating in this project already have great skill in this type of work and are eager to take part in the first systematic studies of the interaction between various types of antibiotics and various types of phages. They have worked on the problems of dangerous infections for many years, particularly in military and severe trauma applications. This project will help them to apply their scientific potential in work for peaceful purposes, especially in enhancing treatment of infectious injuries and diseases. Also, the interest in phage therapy in the USA and Western Europe continues to increase, as proven by formation of new companies and research groups carrying out work on therapeutic applications of bacteriophages

The fundamental and practical parts of this project concerning the treatment of suppurative infections will play a principle role in elaborating technologies for peaceful applications of knowledge in some key areas where research and development were mainly supported by the military.

To achieve our purpose, we consider it crucial to complete the following tasks:

  1. To look in vitro at the effects of each class of antibiotics on phage infection in well-studied pathogenic strains involved in purulent infections, reasonably simulating in vivo conditions (with representatives of each major phage group to be included).
  2. To thoroughly analyze previous cases of application of antibiotics and bacteriophage preparations used during purulent-inflammatory infections, taking into account the best therapeutic effects reported by clinicians, in addition to detailed monitoring of current cases and isolation of bacteria pre and post treatment from new cases.
  3. To determine the sensitivity of these newly isolated bacteria to antibiotics and to study sensitivity and cross resistance of newly isolated bacteria to mono and polyvalent phages approved for therapeutic use.
  4. To precisely determine the medical conditions that can be most effectively included in clinical trials, and to design appropriate phage cocktails, choosing proper regimens for their application.
  5. To carry out small-scale controlled comparative clinical trials on phage versus phage plus antibiotic treatment in 2-3 selected conditions.


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The International Science and Technology Center (ISTC) is an intergovernmental organization connecting scientists from Kazakhstan, Armenia, Tajikistan, Kyrgyzstan, and Georgia with their peers and research organizations in the EU, Japan, Republic of Korea, Norway and the United States.

 

ISTC facilitates international science projects and assists the global scientific and business community to source and engage with CIS and Georgian institutes that develop or possess an excellence of scientific know-how.

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