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Salivary levels of gramicidin after use of a tyrothricin-containing gargle/mouth-wash and tyrothricin lozenges.

Three pharmaceutical preparations for the disinfection of the oropharynx were tested with regard to the gramicidin concentration obtained in the saliva after their appropriate application. Peak values followed a dose-concentration relationship and were highest after sucking a lozenge containing 10 mg tyrothricin (mean 109.3 mg/L) followed by that of a gargle/mouth-wash containing 667 mg tyrothricin/L (mean 21.1 mg/L) and of a lozenge containing 4 mg tyrothricin (mean 14.4 mg/L).

Adult↗

Salivary levels of gramicidin after use of a tyrothricin lozenge and a tyrothricin gargle/mouth-wash.

Salivary levels and total salivary recovery of gramicidin were determined by high performance liquid chromatography in healthy volunteers after administration of a tyrothricin lozenge and a tyrothricin gargle/mouth-wash. Average peak values of gramicidin after sucking the lozenge were 37.5 mg/l and were usually reached within the five minutes. After use of the lozenge mean total recovery of gramicidin in saliva was 44% within the first 30 minutes. After application of the gargle/mouth-wash about 11% was retained in the oral cavity and excreted with saliva within the following 30 minutes. The implications of these findings are discussed.

Adult↗

[Tyrothricin powder in the treatment of cutaneous lesions].

BACKGROUND AND OBJECTIVES: The efficacy and tolerance of an antiseptic wound powder based on the antibiotic tyrothricin was investigated in a prospective, randomized multicenter trial in patients with posttraumatic and surgical cutaneous lesions. PATIENTS AND METHODS: In 5 centers, 131 male and female patients from 18-85 years were included with posttraumatic or surgical cutaneous lesions with infection or in danger of infection (area > or = 200 mm2). In a double-blind study, tyrothricin (n = 62; 0.1 g tyrothricin per 100 g of vehicle) or placebo powder (n = 69) was applied to the wound twice daily for 9 days. The primary aim was to evaluate the average daily reduction of the radius from the lesion area between the start and end of the randomized treatment (alpha = 0.025; one-sided). Secondly, a wound index (range 0-15) was calculated from the assessments of rubor, crusting, exudation, pain and functional impairment. RESULTS: The treatment groups were comparable at baseline. During randomized treatment, the radius of the lesions was reduced at an average of 0.55 +/- 0.31 mm/day (mean +/- SD) for tyrothricin and 0.47 +/- 0.30 mm/day for placebo (p = 0.016; one-sided; intention-to-treat data set). The wound index decreased at an average of 4.2 +/- 1.7 and 3.3 +/- 1.9 points for tyrothricin and placebo, respectively (p = 0.0048; one-sided). 4 adverse events occurred in each group. A causal relationship with the investigational drug could not be excluded in 3 of the placebo group. CONCLUSION: The results confirm the tendency to an acceleration of wound healing by tyrothricin powder (Tyrosur Powder) in case of infection or danger of infection. A superior efficacy compared to placebo was demonstrated. Due to its good tolerability and the absence of a systemic effects tyrothricin powder is appropriate for the treatment of superficial skin lesions.

Adolescent↗

The lytic action of tyrothricin and its derivatives on Staphylococcus aureus.

A tyrothricin concentration of 0.01 mg. per ml. causes rapid lysis of Staphylococcus aureus; this lyric action is not enhanced by phage. A concentration of 0.001 mg. per ml. of tyrothricin is likewise capable of lysing staphylococci, and the addition of phage does not appreciably alter the rate of lysis. A concentration of 0.0001 mg. per ml. of tyrothricin is unable to effect lysis though it enhances the lytic activity of phage. The tyrocidine fraction of tyrothricin appears to be responsible for the latter's lytic action.

Staphylococcal Infections↗

Fungicidal effect of tyrothricin on Candida albicans.

Tyrothricin, a polypeptide antibiotic, is active against yeast cells. Tyrothricin was rapidly fungicidal towards Candida albicans. Concentration of four times the minimum inhibitory (25 mg l-1) reduced the yeast numbers by more than 3 log10 within 1 h. Similar results were obtained in a flow cytometric antifungal activity assay using the new two-colour probe for yeast viability, FUN-1, which measures impairment of metabolic activity. The respiratory activity of Candida albicans, measured in a XTT kinetic assay, was significantly reduced in comparison with controls by 3.12 mg l-1 of the substance. Because fungicidal concentrations of tyrothricin are locally achievable in patients, an evaluation of the local effect of tyrothricin in patients suffering from mucosal infections with Candida species should be considered.

Antifungal Agents↗

GRADIENT PLATE BIOASSAY FOR TYROTHRICIN AND ITS APPLICATION TO DENTIFRICES.

A bioassay for tyrothricin, based on a procedure used by Szybalski in bacterial resistance studies, was developed. Replacement of the tube dilution assay with this procedure represented economy in time and equipment, with a resultant increase in productivity. The procedure involved preparation of special agar plates which provided graded concentrations of tyrothricin along a horizontal axis. A culture dish was inclined, and a base layer of agar, without antibiotic, was poured to cover the bottom of the dish and allowed to harden. A second layer of agar, containing 1 ppm of tyrothricin, was poured and allowed to harden with the dish in a level position. Diffusion of the antibiotic from the top layer into the bottom layer yielded a concentration gradient. A third thin layer of agar seeded with Streptococcus faecalis was poured on the surface. After incubation, a bacterial growth front, representing the minimal effective concentration (MEC), developed. The MEC is expressed as distance (in millimeters) from the edge of the plate. Unknowns were directly related to a standard preparation for calculation of tyrothricin concentration.

Agar↗

In vitro antibacterial activity of gramicidin and tyrothricin.

815 recent clinical isolates of different species representing pathogenic or saprophytic constituents of human microbial flora were submitted to agar dilution tests. In concentrations above 64 micrograms/ml tyrothricin is in general equally as gramicidin or slightly more effective whereas below 8 micrograms/ml gramicidin is mostly more effective than tyrothricin. Of 401 streptococci all were inhibited by tyrothricin and gramicidin in concentrations up to 96 micrograms/ml; staphylococci were more resistant. The pathogenic species of 130 strains of gram-negative cocci were more susceptible than the saprophytic species. Haemophilus strains were mostly resistant to gramicidin and to a lesser extent to tyrothricin. Enterobacteriaceae were totally resistant to both antibiotics.

Bacteria↗

[Antiviral activity of tyrothricin against Sendai virus in suspension tests (author's transl)].

In suspension tests it could be found, that tyrothricin, isolated from bacteria, possesses an anti-infectious activity against Sendai virus. Concentrations of 10(2) to 10(3) ID50-units of Sendai virus were incubated with 0.5 and/or 1.0 mg tyrothricin per 5 ml for 30 minutes at 37 degrees C (pH 7.5). These mixtures were tested in embryonated eggs and showed a marked decrease of viral infectivity. Tween 80 added after the incubation period leads to an incomplete reactivation of the virus infectivity. According to these results and further preliminary studies on herpes simplex virus we suppose a virustatic effect of tyrothricin also in the case of other lipophilic viruses.

Antiviral Agents↗

Adenine nucleotide pool and energy charge during growth of a tyrothricin-producing strain of Bacillus brevis.

The adenine nucleotide levels and derived energy charge value of a tyrothricin-producing strain of Bacillus brevis under aerobic conditions were in good agreement with published values for other bacteria. When growing cultures of B. brevis underwent a transition from aerobic to anaerobic conditions, cyclic variations in the level of adenine nucleotides were observed and the energy charge value oxcillated between 0.87 and 0.70. The significance of these changes is considered in relation to antibiotic production as a possible regulatory mechanism in energy metabolism. It is concluded that tyrothricin is not directly involved in the observed changes in energy charge value.

Adenine Nucleotides↗

[The effect of a formaldehyde-tyrothricin combination placed in periodontal pockets in association with scaling and root planing].

A solution of formaldehyde and tyrothricin was placed in periodontal pockets of 14 patients. One maxillary quadrant was used as the experimental side, while the contralateral quadrant was employed as the control. A placebo solution was placed in the pockets of the control side. Both the experimental and control sides were treated on days -3, 0, +4, +7, +11 and +14. Scaling and root planing was accomplished on day 0. Plaque and gingival indices, and gingival fluid volume were recorded on all of the treatment days, as well as on day +28. Pocket depths were noted on days -3, 0, +14 and +28. Improvements were noted in all parameters measured on both the experimental and control sides, although statistical analyses revealed that plaque and gingival indices were slightly better in the experimental side. The author concludes that placing a Formaldehyde-Tyrothricin solution in periodontal pockets offers some therapeutic gain over scaling and root planing alone.

Adult↗

[The antibacterial activity of a gel for burns and wounds containing tyrothricin, fomocaine, diphenhydramine and 8-hydroxyquinoline (author's transl)].

The antibacterial activity of a new jelly for burns and wounds with the components tyrothricin, 8-hydroxyquinoline, fomocaine and diphenhydramine (Herit) is described. The biological availability of tyrothricin and 8-hydroxyquinoline from the gel is in accordance with minimum inhibitor concentrations (MIC). Against strains of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans the jelly was most effective.

Anti-Bacterial Agents↗

A rapid HPLC method for the quantification of tyrothricin, menthol, and benzocaine in pharmaceutical formulations.

A rapid, sensitive, and accurate reversed-phase HPLC method has been developed for the analysis and quantification of pharmaceutical formulations containing tyrothricin (1), an antibiotic used in antiseptic buccal compressed tablets for local application. The assay has been carried out under isocratic conditions, using a stationary phase of alumina particles coated with polybutadiene and an alkaline mobile phase (pH = 8.2). No HPLC method was reported for the analysis of 1. So, this new technique is an alternative to the slow and tedious microbiological methods. On the other hand, it allows the simultaneous quantification of 1, benzocaine (2), and menthol (3), an aromatic compound not currently analyzed by liquid chromatography.

Benzocaine↗

Development and validation of chromatographic methods (HPLC and GC) for the determination of the active components (benzocaine, tyrothricin and menthol) of a pharmaceutical preparation.

Methods are reported for the determination of tyrothricin and benzocaine by HPLC and menthol by GC in the analysis of throat lozenges (tablets) containing all three compounds. After optimization of the variables involved in both HPLC and GC the methods have been characterized and validated according to the guidelines of the Spanish Pharmacopoeia, and applied to both the monitoring of the manufacturing process and the quality control of the final product.

Anesthetics, Local↗