Physicochemical characterization of hexetidine-impregnated endotracheal tube poly(vinyl chloride) and resistance to adherence of respiratory bacterial pathogens.

PURPOSE: Ventilator-associated pneumonia is a frequent cause of mortality in intensive care patients. This study describes the physicochemical properties of hexetidine-impregnated poly(vinyl chloride) (PVC) endotracheal tube (ET) biomaterials and their resistance to microbial adherence (Staphylococcus aureus and Pseudomonas aeruginosa). METHODS: PVC emulsion was cured in the presence of hexetidine (0-20% w/w) and was characterized in terms of drug release, surface properties (i.e., microrugosity/contact angle), mechanical (tensile) properties, and resistance to microbial adherence. RESULTS: Under sink conditions, hexetidine release from PVC was diffusion-controlled. Increasing the concentration of hexetidine from 1% to 10% (w/w) (but not from 10% to 20% w/w) increased the subsequent rate of drug release. In general, increasing the concentration of hexetidine decreased both the tensile properties and hydrophobicity, yet increased PVC microrugosity. Following hexetidine release (21 days), the surface properties were similar to those of native PVC. The resistance of hexetidine-containing PVC (1% or 5%) to microbial adherence (following defined periods of drug release) was greater than that of native PVC and was constant over the examined period of hexetidine release. CONCLUSIONS: ET PVC containing 1% (w/w) hexetidine offered an appropriate balance between suitable physicochemical properties and resistance to microbial adherence. This may offer an approach with which to reduce the incidence of ventilator-associated pneumonia.

[Hexetidine--an oral antiseptic]. / Heksetidin--oralni antiseptik.

Hexetidine is very safe oral antiseptic with broad antibacterial and antifungal activity in vivo and in vitro. It has local-anesthetics, astringent and deodorant activity. Also, it has very strong antiplac effects. Resistention of microorganisms on hexetidine is short and transient. These characteristics give important therapeutic role in treatment of oral infections.

Determination of the salivary retention of hexetidine in-vivo by high-performance liquid chromatography.

The non-antibiotic antimicrobial agent hexetidine is widely used at a concentration of 0.1% w/v as an oral rinse to reduce the number of viable microorganisms within the oral cavity. However, following use, the available concentration of hexetidine in the oral cavity declines with time, thus compromising the resultant antimicrobial activity. It is, therefore, desirable to determine the persistence of the agent in the oral cavity by quantification of the drug concentration in saliva, thus enabling prediction of its antimicrobial activity in the oral environment. A rapid reverse-phase HPLC method was therefore developed and validated for hexetidine in aqueous solution (Oraldene) and in saliva samples collected from volunteers post-rinsing with 15 mL of hexetidine oral rinse for 30s. The HPLC assay was sufficiently sensitive to accurately detect hexetidine in saliva up to 25 min after in-vivo use of a commercial oral rinse. Furthermore, it was possible to detect hexetidine below the published minimum inhibitory concentrations (MICs) for a selection of microorganisms. From these data a first-order elimination rate constant of hexetidine from the oral cavity was determined post-rinsing in each of six volunteers. The validated HPLC assay method presented is useful for the assay of hexetidine in the oral cavity both at and below MICs. The first-order elimination rate constant shows significant variation between volunteers.

[Stability and new formulations of hexetidine. 2. Formulations and in vitro bioavailability]. / Stabilität und neue Formulierungen von Hexetidin. 2. Mitteilung: Formulierungen und in vitro-Verfügbarkeit.

The solubilization of the water insoluble antimicrobial compound hexetidine is achieved by tensides and cyclodextrins. Using tensides the active ingredient is associated with the lipophilic part of the emulsifier. Tensides with a hydrophilic element in the lipophilic part of the molecule show better solubilizing properties. In contrast a higher stability is achieved with emulsifiers without hydrophilic elements in the lipophilic part of the molecule. The antimicrobial activity, determined by an in vitro test, is not influenced by the type of emulsifier. Cyclodextrins form inclusion complexes with hexetidine. Hydroxy propyl-beta-cyclodextrin is preferred due to its high water solubility. This inclusion complex shows compared with tenside solubilization a better taste and stability. The in vitro antimicrobial activity was comparable to tenside solubilized products.