Effect of antibacterial drugs of the carbapenem group on the composition of the parietal microflora of the large intestine and the pool of free amino acids in the blood plasma of intact rats

Abstract

Introducing the antibiotic therapy into clinical practice is one of the most important steps in the fight against infectious diseases. Antibacterial therapy is prescribed to more than 70 % of all patients in intensive care units. Carbapenems remain the “cornerstone” of antibiotic therapy for severe infections. The main problem on the use of antibiotics is a long-term alteration of the healthy microbiota and a horizontal transfer of resistance genes. The structure of the fund of free amino acids in biological fluids and tissues is an integral characteristic of metabolism, and the effect of antibacterial agents on their concentration in plasma has not been sufficiently studied.The aim of this study was to conduct a comparative analysis of the effects of meropenem and imipenem/cilastatin on the bacterial flora of the intestine and the pool of free amino acids in the blood plasma of rats.The experiments were carried out on white outbred rats kept on a standard vivarium diet and having free access to drinking water. Animals were divided into 3 groups: group 1 (n = 7) – animals were intraperitoneally injected with 0.9 % NaCl solution for 10 days; group 2 (n = 7) – animals were intraperitoneally injected with meropenem-TF (SOOO “TriplePharm”, Republic of Belarus) at a dose of 60 mg/kg body weight for 10 days, group 3 (n = 7) – animals were injected with imipenem in the same way for 10 days /cilastatin (SOOO “TriplePharm”, RB) at a dose of 120 mg/kg of body weight. Free amino acids in blood plasma were determined by chromatography.A comparative analysis of the pool of free amino acids in the plasma of rats after the administration of antibacterial drugs of the carbapenem group revealed a number of significant confidence (p < 0.05) differences in the both study groups. Thus, in the imipenem/cilastatin group, an increase in the total amount of proteinogenic amino acids, essential amino acids, the total amount of aromatic amino acids and a decrease in the nonessential-to essential amino acid ratio were determined. In the meropenem group, these abnormalities were not identified. However, the total amount of sulfur-containing amino acids decreased.The results obtained showed a significant change in the levels of the both individual amino acids and their total amount.  A more pronounced change in the pool of free amino acids in the blood plasma after administrating imipenem/cilastatin is probably due to the presence of cilastatin (renal dehydropeptidase inhibitor) in the composition of the drug, as well as its more pronounced toxicity. When compared with meropenem, imipenem/cilastatin resulted in a greater growth of spore-forming anaerobes. In turn, meropenem more reduced the level of bifidobacteria, lactose-positive bacteria of the E. coli group than  imipenem/cilastatin.