Miramistin

Miramistin is a topical antiseptic with broad antimicrobial action, including activity against biofilms and a clinical profile showing good tolerability. Miramistin was developed within a framework of the Soviet Union Cold War Space Program. It is available for clinical use in several prior Soviet bloc countries, but barely known outside of these countries and there is almost no mention of miramistin in the English literature. However, considering emerging antimicrobial resistance, the significant potential of miramistin justifies its re-evaluation for use in other geographical areas and conditions. The review consists of two parts: (i) a review of the existing literature on miramistin in English, Russian and Ukrainian languages; (ii) a summary of most commonly used antiseptics as comparators of miramistin. The oral LD50 was 1200 mg/kg, 1000 mg/kg and 100 g/L in rats, mice and fish, respectively. Based on the results of the review, we suggest possible applications of miramistin and potential benefits over currently used agents. Miramistin offers a novel, low toxicity antiseptic with many potential clinical uses that need better study which could address some of the negative impact of antimicrobial, antiseptic and disinfectant resistance.

Effects of Miramistin and Phosprenil on biofilms of S. pyogenes, S. aureus, E. coli, L. acidophilus, and L. plantarum were studied. Significant differences in the effects of these substances on mature biofilms of microorganisms and the process of their formation were observed. Miramistin had significant inhibiting effects on the forming of biofilms and on the formed biofilms of all studied microorganisms. Treatment with Miramistin inhibited biofilm formation by 2-3 times compared to the control. This effect was found already after using of Miramistin in the low doses (3.12 μg/ml). Inhibition of the growth of a formed biofilm was observed only after treatment with Miramistin in the high doses (25-50 μg/ml). Phosprenil in the high doses (15-30 mg/ml) inhibited the forming of biofilms, especially the biofilms of S. pyogenes and L. plantarum (by 3-4.5 times). Treatment of formed biofilms with the agent in doses of 6.0 and 0.6 mg/ml was associated with pronounced stimulation of its growth in S. pyogenes, S. aureus, and L. acidophilus.

Background: Miramistin is a widely used antiseptic, disinfectant and preservative, and one of the most popular antimicrobial agents on pharmaceutical market of the Russian Federation (http://www.dsm.ru/en/news/385/). However, there is a lack of reported systematic data on antibacterial efficacy of this agent obtained in accordance with the international standards. Aim: This paper represents a systematic study of antibacterial properties of miramistin. Another objective of this work is to evaluate and compare the exploratory performance of in vitro and in vivo protocols of antiseptics' efficacy testing using miramistin as the reference antiseptic. Methods: Antibacterial activity of 0.1% and 0.2% aqueous solutions of miramistin against two museum strains of S. aureus (ATCC 209p) and E. coli (CDC F-50) was studied. Three standard in vitro laboratory tests (microdilution test, suspension test, and metal surface test), and one in vivo test (on rat's skin) were used. The study was conducted in accordance with the international regulatory documents. Results: Miramistin showed high bactericidal activity against the studied bacterial pathogens in the standard in vitro tests. Thus, in the microdilution test it showed expressed activity against S. aureus (MIC 8 μg/ml, MBC 16 μg/ml) and E. coli (MIC 32 μg/ml, MBC 128 μg/ml). In the suspension test, miramistin decreased the amount of colony forming units by at least 6 log10 units for S. aureus, and by at least 4.5 log10 units for E. coli. Transition to the metal surface test led to significant decrease of antibacterial activity by 1-3 log10 units as compared to the suspension test. Further dramatic reduction of antiseptic activity (by 3-4 log10 units) was observed in in vivo rat skin test. Addition of a protein contaminant (bovine serum albumin) led to a general decrease in the effectiveness of miramistin against the test pathogens (typically, by 1-2 log10 units). An interesting effect of exposure time-dependent reversal of miramistin's specificity to the studied Gram-positive S. aureus and the Gram-negative E. coli organisms was observed in the metal surface test. Conclusions: The results of this work provide systematic data on antibacterial efficacy of miramistin. They also underscore the need in relevant in vivo models for evaluation of antiseptics' efficacy. While the existing in vitro methods can be successfully applied at the discovery stages, it is necessary to use more realistic in vivo models at more advanced development stages. The observed selectivity reversal effect should be taken into account when carrying out the antiseptics' efficacy testing and surface disinfection procedures.