doctoral candidate from 01.01.1993 to 01.01.1998
Kazan, Kazan, Russian Federation
Russian Federation
employee
VAK Russia 4.1.2
VAK Russia 4.1.3
VAK Russia 4.1.4
VAK Russia 4.1.5
VAK Russia 4.2.1
VAK Russia 4.2.2
VAK Russia 4.2.3
VAK Russia 4.2.4
VAK Russia 4.2.5
VAK Russia 4.3.3
VAK Russia 4.3.5
UDC 615
UDC 615.3
UDC 615.9
UDC 616.98
The aim of the study is to evaluate the effect of metallo-β-lactamase inhibitors (MBLIs) on preserving the antimicrobial activity of antibiotics against microorganisms. Objectives: selection, synthesis, and evaluation of complexing agents capable of forming stable complexes with zinc, a metal contained in the active center of MBLIs, and evaluation of their compatibility with antibiotics; determination of the optimal ratio of antibiotic to metallo-β-lactamase inhibitor (MBLI); evaluation of the antimicrobial activity of combinations of an antibiotic with a metallo-β-lactamase inhibitor (MBLI) on a mixed culture of bacterial microorganisms causing diseases of the distal extremities (Staphylococcus spp.) and on a fungal test culture (Candida tropicalis). Data collection and analysis were conducted according to Guideline 4.2.3676-20 "Methods of laboratory research and testing of disinfectants to assess their efficacy and safety" in 2025 in the Veterinary Sanitation Laboratory of the Biotechnology Department of the Federal Center for Toxicology, Radiation, and Biological Safety, as well as in the Mycotoxins Laboratory of the Toxicology Department. Test cultures were obtained from the microorganism collection of the Federal Center for Toxicology and Radiation Safety (FCTRB-VNIVI). The choice of metallo-β-lactamase inhibitor (MBL) components was based on the complexing properties of zinc ions, which are part of the active site of β-lactamases. All test samples with the calculated content of IMBL based on benzylpenicillin, amoxicillin and ceftiofur showed antimicrobial activity against microorganisms (Escherichia coli, Clostridium perfrinens, Streptococcus spp., Staphylococcus spp., Candida tropicalis). The most pronounced antimicrobial and anti-drug resistance activity was observed with ceftiofur and amoxicillin when EDTA, a chelating agent, was added: it increased almost twofold. When using amoxicillin, a pronounced effect was observed when zoledronic acid was used as an IMBLM. However, when using tartrate, the opposite effect was observed. Therefore, tartrate should be excluded from potential IMBLM formulations when using amoxicillin (as well as any antibiotics containing a free phenolic group). High-molecular-weight chelating agents, particularly those like EDTA, exhibit inhibitory effects on mixed microbial cultures, Staphylococcus aureus strains, and even extremely antibiotic-resistant yeasts (Candida tropicalis). The study results will enable the development of new formulations of drugs using IMBLM.
beta-lactam antibiotics, β-lactamases, new metallo-β-lactamase inhibitors, zinc complexes, ceftiofur, amoxicillin, Staphylococcus aureus, Candida tropicalis, mixed culture of microorganisms
1. Gasretova TD, Tyukavkina SYu, Kharseeva GG. Candidiasis. Microbiological diagnostics of candidiasis. In: Textbook. Rostov-on-Don; 2010.
2. Shevyakov MA. Diagnostics and treatment of intestinal candidiasis. Therapeutic archive. 2003;75(11):77-78.
3. Volosach OV. Treatment of candidiasis: possibilities and prospects (literature review). Journal of the Grodno State Medical University. 2014;(2):19-23.
4. Chulkov AK, Ivanov AV, Semenov EI, et al. The problem of mycotoxicoses during import and adaptation of imported cattle. The Veterinarion. 2007;(5):56.
5. Tremasov MYa, Ivanov AV, Papunidi KKh, et al. The problem of mycotoxicoses in animals. The Veterinarion. 2010;(5):16-19.
6. Tremasov MYa, Semenov EI, Tanaseva SA, et al. Mycotoxicosis problems in the Russian Federation. In: International scientific and practical conference “Commodity science and examination, production of food and feed products, ensuring their quality and safety”. Kazan; 2016. P. 224–230.
7. Kryukov SV, Melnik NV, Soloviev BV, et al. Means for veterinary-sanitary and therapeutic measures for bovine necrobacteriosis. The Veterinarion. 2010;(4):7-9.
8. Bakieva FA, Shynybaev KM, Kadyrov OS., et al. Treatment of cattle hoof diseases of necrobacteriosis etiology. Science and Education. 2022;3:35-43.
9. Potekhina RM, Khuzin DA, Titova VYu, et al. Mold fungi and pyogenic bacteria – causes of diseases of fingers and hooves in cows. The Veterinarion. 2021;2:44-49.
10. Nekhaychik FM, Mingaleev DN. Corrosion activity and foaming ability of a new disinfectant. The Veterinarion. 2022;1:26-30.
11. Khuzin DA, Shamilova TA, Tremasova AM, et al. Study of the antimicrobial and fungicidal activity of a product for disinfecting livestock premises in the presence of animals. The Veterinarion. 2023;4:20-26.
12. Perfilova KV, Kashevarov GS, Saitov VR, et al. Evaluation of ultrastructural changes in Fusobacterium necrophorum under the influence of agents used for group prevention of distal limb diseases in ungulates. Bulletin of the Kursk State Agricultural Academy. 2023;1:153-158.
13. Matrosova LE, Cherednichenko YuV, Matveeva EL, et al. A case of candidiasis in ducks. Advances in Medical Mycology. 2016;16:216.
