Antimicrobial activity microbicidal

Recently, the activities of host defense peptides related to the resolution of infection have been suggested to result in part from nondirect antimicrobial activities. It has been postulated that immunomodulation may represent the primary action of these peptides in vivo as the immunomodulatory activities are retained under physiological conditions in contrast to the direct antimicrobial activities of most natural mammalian host defense peptides. These immunomodulatory activities include, but are not limited to, direct chemotactic activity, induction of chemokines and other immune mediators, stimulation of leukocyte degranulation and other microbicidal activities, effects on leukocyte and epithelial cell survival and apoptosis, stimulation of epithelial and endothelial cell proliferation, promotion of wound healing and angiogenesis, antiendotoxic and anti-inflammatory activities, and adjuvant fiinctions. These will be described in detail in the following sections and a summary is found in Table 1. 

The ambient medium impairs the effectiveness of microbicides also if its constituents include those capable of interacting with a microbicide in competition with the constituents of the microbe cell. This is true of electrophilically active microbicides in general as far as the ambient medium contains nucleophilically active constituents with which the microbicide can react in competition with the corresponding cell constituents. It is also true, however, of membrane-active microbicides if adsorption of the microbicide on organic matter competes with the adsorptive processes on the cytoplasmic membrane or if such microbicides, e.g. phenol derivatives, become incorporated in micelles that are formed in certain media at levels above the critical micelle concentration with the result that the incorporated active substance molecules are no longer available for the antimicrobial effect (see III. 16, Fig. 34). 

The effectiveness and efficiency of microbicides result from the interplay of the chemicophysical properties of the active substance molecule, which are determined by the molecule s constitution. Solubility, polarity, ionicity and reactivity are examples of properties that influence effectiveness. Taking the N-trihalo-methylthio derivative as examples, Paulus Kiihle (1986) drew attention to an important principle that evidently applies to electrophilically active microbicides in general, namely that the relationship shown in Fig. 11 exists between the antimicrobial effectiveness and reactivity of microbicide molecules. As the reactivity increases, so, too, does the effectiveness—until it peaks at a moderately high reactivity level. Thereafter the antimicrobial activity decreases as the reactivity continues to rise because at this stage competition reactions — interactions of the reactive microbicide molecules with constituents of the surrounding medium — predominate. 

As a rule it has to be stated that halogenated alkylphenols are more active and broader in effectiveness than the alkylphenols. It is therefore in no way astonishing that some of the most important phenol derivatives in practical application are found in this class of phenolics. Among others Klarmann et al. (1933) have carried out systematic examinations of the relationship between chemical structure and antimicrobial activity with regard to halogenated alkylphenols. However, one should not overestimate the value of the data obtained when decisions and selections have to be made for practical application, as other properties of the microbicidal compounds, such as water-solubility, partition coefficient, activity in the presence of interfering factors encountered in practice, and toxicity, are of the same or of even more importance. Although there are available a lot of data and experience, often the optimum compound and formulation must be determined by experiment. 

Due to its moderate antimicrobial activity the compound has not gained importance as a microbicide in practice. 

The microbicidal acids belong to the membrane-active substances. Typical is that acids display significant antimicrobial activity only when they are present in their undissociated state. A carboxylic acid for instance dissociates according to the following equation... 

IPPC is a broad spectrum fungicide as is IPBC (Section 9.1). As can be seen from Table 86 the antimicrobial activity is also against yeasts and algae. IPPC may be used in fields of application which are described for IPBC. In exposure tests with paint films IPPC containing coatings appeared to be of somewhat longer lasting effectiveness in comparison to IPBC, which apparently is a little more leachable. However, up to now IPPC is not a commercially available microbicide. 

The microbicides given in Sections 9.7 and 9.8 are novel benzoxalone compounds. Their antimicrobial activity, mainly directed against fungi and their utility as microbicides is described by Chi-Tung Hsu (1991). 

Although Zineb displays a broad spectrum of effectiveness and considerable antimicrobial activity, it has not often been employed as a microbicide for the protection of materials. The stable Ziram (see Section 9.10.2) is the preferred zinc dithiocarbamate for that application. The disodium salt of ethylenebisdithio-carbamic acid (Nabam) is also available. 

Among other pyridine derivatives 2-hydroxy-pyridine-AT-oxides, 2-mercapto-pyridine- -oxides and 8-hydroxyquinolines are described in this section which may be looked at as membrane-active microbicides with chelating properties. The following pyridine compounds with antimicrobial activity but without significant importance for the protection of materials shall only be mentioned ... 

The antimicrobial activity of dioctyl-dimethylammonium chloride corresponds to that of other QACs. Concentrations of 5-15 mg/litre are algicidal for fresh water algae. As the active concentrations of dioctyl-dimethylammonium chloride do not foam the microbicide is preferably used as a slimicide and algicide for water treatment. 

TBTL is a microbicide of minor importance in the field of material protection its antimicrobial activity corresponds to that of TBTN (Section 17.7.1). 

Membrane-active microbicides include alcohols - phenols - acids- saHcylanilides - carbanOides - dibenzamidines -biguanides - quaternary ammonium salts and other active ingredients with cationic character, e.g. azole fungicides which also act as chelate formers. As many of the antimicrobial agents which are able to complex metal cations display membrane-activity, they will be considered here as membrane-active microbicides. 

Other authors reported no microbicidal effect of silver. The survival of three bacterial species and C. albicans on a silver-impregnated polymer was not found to be influenced by the silver incorporation (Kampf et al., 1998). Using confocal laser scanning microscopy, Cook et al. (2000) observed that a silver-coated prosthetic heart valve sewing cuff was colonized by a higher number of bacteria S. epidermidis) than an uncoated cuff. McLean et al. (1993) reported that only a combination of silver and copper in multilayer surface films on catheter materials provided enhanced antimicrobial activity compared to uncoated or only silver-coated surfaces. 

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