Antimicrobial effects of pharmaceutical compositions of nisin with auxiliary components

Abstract

Introduction. One of the promising methods of combating antibiotic resistance can be the combination of nisin with helper substances that do not have a direct antimicrobial effect, but in one way or another bind the resistance factors of bacteria, restoring their sensitivity to classical antibiotics. The search for helper substances among already known and well-studied substances is considered a promising direction in the fight against the resistance of microorganisms. The aim of the work is the microbiological substantiation of the feasibility of creating pharmaceutical compositions based on nisin with auxiliary substances for the treatment of infectious and purulent-inflammatory diseases. Materials & methods. The antimicrobial activity of 1.0% aqueous solutions of unmodified and modified nisin with helper substances was determined. Modified nisin was obtained by acylation of nisin with acetic anhydride. Diclofenac sodium and amlodipine are used as auxiliary substances. 17 clinical strains of microorganisms were used for microbiological research. The antimicrobial activity of substances and their combinations was determined by the diffusion method of "wells" with the measurement of the diameters of the zones of growth retardation of microorganisms. Results & discussion 1.0% aqueous solutions of unmodified nisin and amlodipine in isolated form exerted mainly a weak antimicrobial effect on gram-positive microorganisms. Moderate sensitivity of clinical strains of S. epidermidis and weak sensitivity of S. aureus and E. faecalis to sodium diclofenac was established. With regard to clinical strains of gram-negative microorganisms, all investigated substances in isolated form were inactive or weakly active. When combining unmodified nisin, diclofenac sodium and amlodipine, an increase in the antimicrobial effect of the combinations was observed to a high level against some clinical strains of S. epidermidis and to a moderate level against the remaining clinical strains of gram-positive microorganisms and E. coli. When combining 1.0% aqueous solutions of unmodified nisin, diclofenac sodium and amlodipine in all cases, their antimicrobial activity against clinical strains of S. aureus increased to moderate. Clinical strains of S. epidermidis showed the greatest sensitivity to combinations of unmodified nisin, diclofenac sodium and amlodipine. Regarding all investigated representatives of the genus Streptococcus, the effect of combinations of unmodified nisin with diclofenac sodium and the triple combination of nisin, diclofenac and amlodipine was moderate. However, half of the studied strains of Streptococcus spp. were generally insensitive to the combination of unmodified nisin and amlodipine. Regarding the studied clinical strains of E.faecalis, the antimicrobial effect of all studied combinations of substances was moderate. As a result of experiments with gram-negative clinical strains of microorganisms, it was established that E.coli strains were moderately sensitive to all tested combinations of unmodified nisin, sodium diclofenac and amlodipine. Representatives of Proteus spp. were insensitive to double combinations of unmodified nisin with diclofenac sodium and nisin with amlodipine. The triple combination of unmodified nisin, diclofenac sodium and amlodipine was effective on clinical strains of Proteus spp. weak antimicrobial effect. When combining 1.0% aqueous solutions of acetylated nisin, diclofenac sodium and amlodipine in all cases of a double combination, the antimicrobial activity against clinical strains of S. aureus and S. epidermidis increased to a moderate level, and to a high level in relation to the triple combination. Regarding the representatives of Streptococcus spp., E.faecalis and gram-negative microorganisms, the antimicrobial effect of all studied combinations was moderate. Conclusion.  1. When combining unmodified nisin, diclofenac sodium and amlodipine, an increase in the antimicrobial effect of the combinations was observed to a high level in relation to some of the clinical strains of S. epidermidis and to a moderate level in relation to the rest of the clinical strains of gram-positive microorganisms and E.coli. 2. When combining unmodified nisin, diclofenac sodium and amlodipine, their triple combination was the most effective, which, in addition to a high antimicrobial effect against 50.0% of clinical strains of S. epidermidis and a moderate one against S. aureus, E.faecalis, the remaining strains of S. epidermidis and E.coli showed a weak antimicrobial effect against the studied clinical strains of Proteus spp.3. When combining acetylated nisin, diclofenac sodium and amlodipine, an increase in the antimicrobial effect of the combinations was observed against both gram-positive and gram-negative microorganisms. 4. In a comparative analysis of the antimicrobial activity of 1.0% aqueous solutions of unmodified nisin, diclofenac sodium, amlodipine in isolated form and their combinations, as well as acetylated nisin in combinations with diclofenac sodium and amlodipine, the most effective against the studied clinical strains of gram-positive and gram-negative microorganisms a triple combination of 1.0% aqueous solutions of acetylated nisin, diclofenac sodium and amlodipine was found.

Key words: nisin, acetylated nisin, auxiliary components, diclofenac sodium, amlodipine, pharmaceutical compositions, microorganisms, antimicrobial activity