Profile of antibiotic resistance of Staphylococcus aureus isolated from patients and bacterial carriers of the Astrakhan region as the basis for the selection of bacteriophage producing strains for further combined phage therapy

Staphylococcus aureus has a high level of antibiotic resistance and is a common cause of nosocomial infections, which primarily requires development of new therapeutic strategies.

Aim of the study was to investigate the level and spectrum of antibiotic resistance of S. aureus isolates for further isolation of virulent bacteriophages.

Material and methods. The study used samples of clinical material obtained on the basis of the City Clinical Hospital No. 3 named after S.M. Kirov (Astrakhan). Bacterial strains isolated from patients were identified on the basis of morphological, cultural, biochemical and molecular genetic characteristics. The determination of the resistance of the isolated cultures was carried out by the disco-diffusion method using standardized commercial discs with antibiotics, in accordance with the guidelines.

Results. Evaluation of antibiotic resistance of Staphylococcus aureus isolated during the study of clinical material from patients and analysis of sensitivity level of isolated strains of S. aureus allow us to conclude that all S. aureus isolated from patients are resistant to at least one antibiotic, and most strains are characterized by multidrug resistance to antibiotics.

Conclusions. The presence of multi-resistant strains indicates the need to search for new approaches in the treatment of staphylococcal infection and to develop effective means for combination therapy based on virulent staphylococcal bacteriophages.

1. Plumet L., Ahmad-Mansour N., Dunyach-Remy C., Kissa K., Sotto A., Lavigne J.P., Costechareyre D., Molle V. Bacteriophage therapy for Staphylococcus aureus infections: a review of animal models, treatments, and clinical trials. Front. Cell. Infect. Microbiol. 2022;12:907314. doi: 10.3389/fcimb.2022.907314

2. Ahmad-Mansour N., Loubet P., Pouget C., Dunyach-Remy C., Sotto A., Lavigne J.P., Molle V. Staphylococcus aureus toxins: an update on their pathogenic properties and potential treatments. Toxines (Basel). 2021;13(10):677. doi: 10.3390/toxins13100677

3. Tokaeva B.T., Kimalyakova Kh.Kh., Ugusheva D.Kh., Shikhova T.S. Analysis of sensitiveness of Staphylococcus aureus to the antibiotics. Nauka i zdravookhraneniye = Science and Healthcare. 2014;(2):92–94. [In Russian].

4. Roca I., Akova M., Baquero F., Carlet J., Cavaleri M., Coenen S., Cohen J., Findlay D., Gyssens I., Heuer O.E., ... Vila J. The global threat of antimicrobial resistance: science for intervention. New Microbes New Infect. 2015;6:22–29. doi: 10.1016/j.nmni.2015.02.007

5. Namazova-Baranova L.S., Baranov A.A. Antibiotic resistance in the modern world. Pediatricheskaya farmakologiya = Pediatric Pharmacology. 2017;14(5):341–354. [In Russian]. doi: 10.15690/pf.v14i5.1782

6. Kwiecinski J.M., Horswill A.R. Staphylococcus aureus bloodstream infections: pathogenesis and regulatory mechanisms. Curr. Opin. Microbiol. 2020;53:51– 60. doi: 10.1016/j.mib.2020.02.005

7. King D.T., Sobhanifar S., Strynadka N.C.J. One ring to rule them all: Current trends in combating bacterial resistance to the beta-lactams. Protein Science. 2016;25(4):787–803. doi: 10.1002/pro.2889

8. Turner N.A., Sharma-Kuinkel B.K., Maskarinec S.A., Eichenberger E.M., Shah P.P. Carugati M., Holland T.L., Fowler V.G. Methicillin-resistant Staphylococcus aureus: overview of basic and clinical research. Nat. Rev. Microbiol. 2019;17(4):203–218. doi: 10.1038/s41579-018-0147-4

9. Kolenda C., Medina M., Bonhomme M., Laumay F., Roussel-Gaillard T., Martins-Simoes P., Tristan A., Pirot F., Ferry T., Laurent F., PHAGEinLYON Study Group. Phage therapy against Staphylococcus aureus: selection and optimization of production protocols of novel broad-spectrum silviavirus phages. Pharmaceutics. 2022;14(9):1885. doi: 10.3390/pharmaceutics14091885

10. Atshan S.S., Hamat R.A., Aljaberi M.A., Chen J.S., Huang S.W., Lin C.Y., Mullins B.J., Kicic A. Phage therapy as an alternative treatment modality for resistant Staphylococcus aureus infections. Antibiotics (Basel). 2023;12(2):286. doi: 10.3390/antibiotics12020286

11. Kebriaei R., Lehman S.M., Shah R.M., Stamper K.C., Kunz Coyne A.J., Holger D., El Ghali A., Rybak M.J. Optimization of phage-antibiotic combinations against Staphylococcus aureus biofilms. Microbiol. Spectr. 2023;11(3): e0491822. doi: 10.1128/Spectrum.04918-22

12. Shepelin A.P., Domotenko L.V. Disk diffusion method for determining the sensitivity of microorganisms to antibacterial drugs. Poliklinika = Polyclinic. 2019;4(1):2–5 [In Russian].