The combined influence of a metabolite complex of Lactobacillus rhamnosus GG and Saccharomyces boulardii with amikacin on infected wounds in models in vivo




metabolites, antibiotics, multiresistant bacteria, infected wounds, synergistic activity



The aim of the work – to study in vivo the effectiveness of the simultaneous and alternate use of the Lactobacillus rhamnosus GG and Saccharomyces boulardii metabolite complex with an antibacterial preparation in a guinea pig model of skin wound infected with a multiresistant Pseudomonas aruginosa strain to validate prospects for its application in the development of add-on preparations to antibiotic therapy.

Materials and methods. The metabolite complex of lactobacteria and saccharomycetes was obtained by culturing cells of probiotic microorganisms in their own ultrasonic disintegrates (MLS). The following were applied to wounds infected with the multiresistant strain of P. aeruginosa twice daily: 0.9 % sodium chloride solution (control group, К), amikacin – AB (group L I), simultaneously AB with MLS (group L II), alternately AB and MLS (group L III). The dynamics of planimetric indicators of wounds (sizing, calculation of the healing area, healing rate, healing rate coefficient, reparative effect) was carried out on days 1, 5, 8 and 11. Antimicrobial activity was evaluated by bacteriological examination of a material from wound samples with identification and determination of the number of colony forming units (CFU) of the pathogen.

Results. The combined anti-pseudomonas activity of amikacin and the L. rhamnosus GG and S. boulardii metabolite complex was established. Decreased CFU of P. aeruginosa and acceleration of reparative processes in wounds were observed in groups L I, L II, L III compared to K on days 5 and 8 (P < 0.05). The greater effectiveness of the first proposed alternate method of using AB and MLS was proved in contrast with their simultaneous application. The wound surface areas in L III group were smaller relative to L II (1.8 and 5.0 times, P = 0.03), and L I (2.8 and 9.0 times, P = 0.04) on days 5 and 8, respectively. The increase in synergistic antimicrobial activity due to the new approach of alternate effect was probably due to an increase in antibiotic susceptibility of the test cultures.

Conclusions. The presented in the work results of the pronounced synergistic effect of combined using amikacin and the metabolite complex of Lactobacillus rhamnosus GG and Saccharomyces boulardii confirm its promise for practical medicine and the pharmaceutical industry. The data obtained open the potential for developing add-on preparations to antibiotic therapy based on metabolite complexes for the treatment of infected wounds.


World Health Organization. (2017, February 27). WHO publishes list of bacteria for which new antibiotics are urgently needed.

Fomicheva, T. D., Turkutyukov, V. B., Sotnichenko, S. A., Terekhov, S. M., Skurikhina, Yu. E., & Okrokov, M. V. (2018). Mikrobiologicheskii monitoring v sisteme epidemiologicheskogo nadzora za gnoino-septicheskimi infektsiyami pri ozhogovoi travme [Microbiological monitoring in the epidemiological surveillance system for purulent-septic infections in case of burn injury]. Tikhookeanskii meditsinskii zhurnal, (3), 72-74. [in Russian].

Fadeev, S. B. (2013). Dinamika vidovogo sostava mikroflory ochagov khirurgicheskoi infektsii myagkikh tkanei v techenie zabolevaniya [The dynamics of species structure of microflora of foci surgical soft tissue infection in the course of the disease]. Byulleten' Orenburgskogo nauchnogo tsentra UrO RAN, (3), 1-12. [in Russian].

Buliga, L. A., Chernykh, V. P., Movchan, B. A., Shtrygol, S. Y., Butko, Y. A., Ruban, E. A., & Gorbach, T. V. (2015). Izuchenie ranozazhivlyayushchego deistviya gelei s nanochastitsami serebra u zhivotnykh s gnoinymi ranami [The studies of wounds healing activity of gels with nanoparticles of silver in animals with purulent wounds]. Vestnik farmatsii, (2), 62-68. [in Russian].

Balabekyan, T. R., Karapetyan, K. J., Khachatryan, T. V., Khachatryan, G. E., & Tatikyan, S. S. (2018). Antimicrobial activity of preparations after combined cultivation of lactic acid bacteria and yeast strains. Journal of Animal Physiology and Animal Nutrition, 102(4), 933-938.

Isayenko, O. Y. (2019). Protydyfteriini vlastyvosti strukturno-metabolitnykh kompleksiv probiotychnykh shtamiv laktobakterii i sakharomitsetiv u testakh in vitro ta in vivo [Anti-diphtheria properties of structural-metabolites complexes of Lactobacteria and Saccharomyces probiotic strains]. Fiziolohichnyi zhurnal, 65(6), 51-60. [in Ukrainian].

Isayenko, O. Y. (2019). Synergistic activity of filtrates of Lactobacillus rhamnosus and Saccharomyces boulardii and antibacterial preparations against Corynebacterium spp. Regulatory Mechanisms in Biosystems, 10(4), 445-456.

Hanchi, H., Hammami, R., Gingras, H., Kourda, R., Bergeron, M. G., Ben Hamida, J., Ouellette, M., & Fliss, I. (2017). Inhibition of MRSA and of Clostridium difficile by durancin 61A: synergy with bacteriocins and antibiotics. Future Microbiology, 12(3), 205-212.

Valyshev, A. V., & Valysheva, N. A. (2016). Kombinatsiya antibiotikov i bakteriotsinov - effektivnyi sposob bor'by s rezistentnymi mikroorganizmami [Combination of antibiotics and bacteriocins – effective way for fighting resistance microorganisms]. Byulleten' Orenburgskogo nauchnogo tsentra UrO RAN, (4), 1-6. [in Russian].

Isaienko, O. Yu, Kotsar, O. V., Ryzhkova, T. M., & Babych, Ye. M. (2020). Protymikrobna aktyvnist strukturno-metabolitnykh kompleksiv L. rhamnosus GG i S. boulardii shchodo S. aureus ATSS 25923, E. coli ATCC 25922, R. aeruginosa ATCC 27853 [Antimicrobial activity of structural-metabolic complexes of L. rhamnosus GG and S. boulardii against S. aureus AТСС 25923, E. coli ATCC 25922, Р. аеruginosa ATCC 27853]. Zaporozhye medical journal, 22(4), 540-546. [in Ukrainian].

Xu, L., McLennan, S. V., Lo, L., Natfaji, A., Bolton, T., Liu, Y., Twigg, S. M., & Yue, D. K. (2007). Bacterial Load Predicts Healing Rate in Neuropathic Diabetic Foot Ulcers. Diabetes Care, 30(2), 378-380.

Heunis, T. D., Smith, C., & Dicks, L. M. (2013). Evaluation of a Nisin-Eluting Nanofiber Scaffold To Treat Staphylococcus aureus-Induced Skin Infections in Mice. Antimicrobial Agents and Chemotherapy, 57(8), 3928-3935.

Isaienko, O. Yu., Knysh, O. V., Babych, Ye. M., Kompaniets, A. M., Osetsky, O. I., Polianska, V. P., & Zachepylo, S. V. (2017). Vplyv umov zberihannia filtrativ bulionnykh kultur probiotykiv na yikhniu protymikrobnu aktyvnist [Influence of Storage of Probiotic Broth Culture Filtrates on Their Antimicrobial Activity]. Problems of Cryobiology and Cryomedicine, 27(4), 311-321. [in Ukrainian].

Samaeva, E. (2016). Sravnitel'naya kharakteristika osobennostei techeniya regeneratornykh protsessov pri peresadke kul'tivirovannykh dermal'nykh autofibroblastov i lechenii maz'yu «Levomekol'» [The comparative analysis of regenerative processes flow phenomena when transplanting incubate dermal auto-fibroblasts and treatment with the ointment «Levomekol»]. Universum: meditsina i farmakologiya, (6). [in Russian].

Jabés, D., Brunati, C., Candiani, G., Riva, S., Romanó, G., & Donadio, S. (2011). Efficacy of the New Lantibiotic NAI-107 in Experimental Infections Induced by Multidrug-Resistant Gram-Positive Pathogens. Antimicrobial Agents and Chemotherapy, 55(4), 1671-1676.

Zvyagintseva, T. V., & Khalin, I. V. (2011). Metabolitotropnaya terapiya khronicheskikh ran [Metabolitotropic therapy of chronic wounds]. FOP Vyrovets A. P. [in Russian].

Isayenko, O. Y., Knysh, O. V., Babych, Y. M., Ryzhkova, T. N., & Dyukareva, G. I. (2019). Effect of disintegrates and metabolites of Lactobacillus rhamnosus and Saccharomyces boulardii on biofilms of antibiotic resistant conditionally pathogenic and pathogenic bacteria. Regulatory Mechanisms in Biosystems, 10(1), 3-8.

Isayenko, O. Y., Knysh, O. V., Kotsar, O. V., Ryzhkova, T. N., & Dyukareva, G. I. (2020). Simultaneous and sequential influence of metabolite complexes of Lactobacillus rhamnosus and Saccharomyces boulardii and antibiotics against poly-resistant Gram-negative bacteria. Regulatory Mechanisms in Biosystems, 11(1), 139-145.

Ribeiro, S. M., de la Fuente-Núñez, C., Baquir, B., Faria-Junior, C., Franco, O. L., & Hancock, R. E. (2015). Antibiofilm Peptides Increase the Susceptibility of Carbapenemase-Producing Klebsiella pneumoniae Clinical Isolates to β-Lactam Antibiotics. Antimicrobial Agents and Chemotherapy, 59(7), 3906-3912.

How to Cite

Isaienko OY, Minukhin VV, Ryzhkova TM, Kotsar OV. The combined influence of a metabolite complex of Lactobacillus rhamnosus GG and Saccharomyces boulardii with amikacin on infected wounds in models in vivo. Zaporozhye Med J [Internet]. 2020Dec.9 [cited 2023Dec.5];22(6). Available from:



Original research