Evaluation of pathogenetic features of antibiotic-associated syndrome using a biological model
Authors:   Central Research Institute of Epidemiology of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Moscow, Russian Federation, Ploskireva A.A. , Gorelov A.V. ,   Central Research Institute of Epidemiology of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Moscow, Russian Federation,   A.I.Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russian Federation, Golden L. ,   Central Research Institute of Epidemiology of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Moscow, Russian Federation, Nikolaeva S.V. ,   Central Research Institute of Epidemiology of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Moscow, Russian Federation, Simkova E.Yu. ,   Central Research Institute of Epidemiology of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Moscow, Russian Federation
Published: July 2023

Antibiotic therapy is an integral part of current therapeutic practice to save patients’ lives. However, as with any therapeutic intervention, the development of adverse events is possible, one of which is the antibiotic-associated syndrome (AAS). Objective. To study the pathogenetic features of AAS extraintestinal manifestations using a biological model as an example. Materials and methods. This study was conducted using the biological model (outbred male mice) between 2019 and 2020 on the basis of the Central Research Institute of Epidemiology of Rospotrebnadzor. Experimental animals were injected with amoxicillin/clavulanic acid and cefotaxime in two therapeutic doses, average and maximum. The recalculation of drug doses was carried out depending on the animal’s body weight. The comparison was performed in four study groups and one control group, which were distinguished according to the dose and type of antibacterial agent. The histological examination of internal organs (large intestine, small intestine, liver, pancreas, kidney, lung, heart, testicles, spleen, stomach, duodenum, skin, bladder) was conducted at two time points: 24 hours after antibiotic administration and 7 days after the end of antibiotic therapy. Results. The results of histological examination at the first time point (24 hours after antibiotic administration) demonstrated that the use of the studied antibacterial agents at the average therapeutic dose did not cause significant morphological changes in the organs of mice, while the administration of maximum dose led to the development of reactive changes, primarily in the vascular system. The results of histological examination in the experimental groups at the second control time point (7 days after the end of antibiotic therapy) showed a systemic reaction in the organs of mice, expressed primarily in perivascular leukocyte infiltration. Similar changes were registered in the group of experimental animals that were injected with average therapeutic doses of antibacterial agents. Conclusion. AAS is characterized by systemic and homogeneous pathomorphological changes in various tissues, which explains not only the development of antibiotic-associated diarrhea, but also its extraintestinal symptoms. Our findings allow to suggest that antibiotics, especially when used irrationally, increase the risks of pathology associated with a systemic inflammatory response, in particular atherosclerosis and obesity, at the population level. Key words: antibiotic-associated diarrhea, antibiotic-associated syndrome