Therapeutic potential of highly diluted antibodies in antibiotic-resistant infection

Klebsiella pneumoniae is one of the main causes of hospital-acquired infections. Its rate of antimicrobial resistance is rapidly increasing, while there are no licensed human vaccines against it. A novel therapeutic approach involves modulation of the host immune response combined with antibiotic tr...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2022-06, Vol.173, p.106161-106161, Article 106161
Main Authors: Emelianova, Alexandra G., Petrova, Natalia V., Fremez, Christophe, Fontanié, Maxime, Tarasov, Sergey А., Epstein, Оleg I.
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
antibodies
antimicrobial resistance
Cross Infection
immunomodulation
Klebsiella Infections - drug therapy
Klebsiella Infections - microbiology
Klebsiella pneumoniae
MHC I
MHC II
Mice
Microbial Sensitivity Tests
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Summary:Klebsiella pneumoniae is one of the main causes of hospital-acquired infections. Its rate of antimicrobial resistance is rapidly increasing, while there are no licensed human vaccines against it. A novel therapeutic approach involves modulation of the host immune response combined with antibiotic treatment. One of the approaches to immunomodulation can be the use of antibodies (Abs) in a specific technological form of high dilutions (hd). The aim of the study was to assess whether hd-Abs could affect the antibacterial activity of AMC against a bacterial strain resistant to it. The study was performed on an in vivo model of K. pneumoniae BAA-1705 multiresistant strain lethal infection in neutropenic RjOrl:Swiss mice. The efficacy of hd-Abs combined with AMC was assessed based on survival and lung bacterial burden. Additionally, we evaluated the direct effect of the drugs on the growth of bacteria in vitro. hd-Abs in combination with AMC increased survival of mice infected with K. pneumoniae up to 50%, whereas all animals in the AMC group died. Hd-Abs had no direct effect on K. pneumoniae sensitivity to AMC in vitro. The survival rate in mice treated with hd-Abs combined with AMC was comparable to that in animals treated with the reference drug gentamicin. Thus, hd-Abs increased the antibacterial activity of AMC against the strain resistant to it. The mechanism of action of hd-Abs remains to be elucidated in future studies. [Display omitted]
ISSN:0928-0987
1879-0720
DOI:10.1016/j.ejps.2022.106161