Antimicrobial agents selection

Spontaneous mutation brings about organisms with novel antibiotic resistance mechanisms. If these cells are viable, in the presence of the antimicrobial agent selective multiplication of the resistant strain occurs so that it eventually dominates as above. 

Adhesive compositions for reducing, inhibiting and/or preventing calculus, tartar, plaque and/or microbes in the oral cavity comprise from about 15 to 70% of an alkyl vinyl ether maleic copolymer or terpolymer denture adhesive component, an effective amount of a quaternary ammoiuum antimicrobial agent selected from the group consisting of cetylpy ridinium chloride, domiphenbromide or mixtures thereof, and a non-aqueous vehicle. 

Uses. Silver fluoride has found many laboratory and special industrial appHcations. It is used as a soft (nHld) fluorinating agent for selective fluorination (7—17), as a cathode material in batteries (qv) (18), and as an antimicrobial agent (19). Silver fluoride is commercially available from Advance Research Chemicals, Inc., Aldrich Chemicals, Cerac Corp., Johnson/Matthey, PCR, Atochem, and other sources in the United States. The U.S. price of silver fluoride in 1993 was 1000— 1400/kg and the total U.S. consumption was less than 200 kg/yr. 

Industrial antimicrobial agents are chemicals used to prevent the adverse consequences of microbiological activity in processes and products. Some are unique to this segment and others are drawn from the antimicrobial agents used in medicine, agriculture, and sanitary appHcations. Industrial antimicrobials are selected where process or stricdy physical conditions, such as irradiation or heat, are impractical or ineffective in controlling microbiological activity. 

To retain solutes selectively by dispersive interactions, the stationary phase must contain no polar or ionic substances, but only hydrocarbon-type materials such as the reverse-bonded phases, now so popular in LC. Reiterating the previous argument, to ensure that dispersive selectivity dominates in the stationary phase, and dispersive interactions in the mobile phase are minimized, the mobile phase must now be strongly polar. Hence the use of methanol-water and acetonitrile-water mixtures as mobile phases in reverse-phase chromatography systems. An example of the separation of some antimicrobial agents on Partisil ODS 3, particle diameter 5p is shown in figure 5. 

Susceptibility of viruses to antimicrobial agents can depend on whether the viruses possess a lipid envelope. Non-lipid viruses are frequently more resistant to disinfectants and it is also likely that such viruses cannot be readily categorized with respect to their sensitivities to antimicrobial agents. These viruses are responsible for many nosocomial infections, e.g. rotaviruses, picornaviruses and adenoviruses (see Chapter 3), and it may be necessary to select an antiseptic or disinfectant to suit specific circumstances. Certain viruses, such as Ebola and Marburg which cause haemorrhagic fevers, are highly infectious and their safe destruction by disinfectants is of paramount importance. 

The intended application of an antimicrobial agent, whether for preservation, antisepsis or disinfection, will influence its selection and also affect its performance. For example, in medicinal preparations the ingredients in the formulation may antagonize preservative activity. The risk to the patient will depend on whether the antimicrobial is in close contact with a break in the skin or mucous membranes or is introduced into a sterile area of the body. 

Host factors can help to ensure selection of the most appropriate antimicrobial agent. Age is an important factor in antimicrobial selection. With regard to dose and interval, renal and hepatic function varies with age. Populations with diminished renal function include neonates and the elderly. Hepatic function in the neonate is not fully developed, and drugs that are metabolized or eliminated by this route may produce adverse effects. For example, sulfonamides and ceftriaxone may compete with bilirubin for binding sites and may result in hyperbilirubinemia and kernicterus. Gastric acidity also depends on... 

Figure 66-4 provides an overview of patient- and antimicrobial agent-specific factors to consider when selecting an antimicrobial regimen. It further delineates monitoring of therapy and actions to take depending on the patients response to therapy. The duration of therapy depends on patient response and type of infection being treated. 

The severity of a patient s infection, based on the PEDIS scale, guides the selection of empirical antimicrobial therapy. While most patients with grade 2 diabetic foot infections can be treated as outpatients with oral antimicrobial agents, all grade 4 and many grade 3 infections require hospitalization, stabilization of the patient, and broad-spectrum IV antibiotic therapy.31... 

Figure 4 Stabilized bromine antimicrobials are produced by eosinophils, a type of mammalian white blood cell. Bacteria are captured by phagocytosis and contained intracellularly within vesicles called phagosomes. Granules release cationic surfactants, lytic enzymes, and eosinophil peroxidase into the phagosome in a process known as degranulation. Eosinophil peroxidase, an enzyme that is structurally similar to the bromoperoxidases found in seaweed (Figure I), selectively catalyzes oxidation of bromide to hypobromite by reducing hydrogen peroxide to water. The hypobromite immediately reacts with nitrogenous stabilizers such as aminoethanesulfonic acid (taurine) to form more effective and less toxic antimicrobial agents.

Nebulizer formulation conforms to sterile product preparation, which means that drug stability in solution in the presence of additives must be evaluated. Historically, it was sufficient to use antimicrobial agents in the formulation, notably benzalkonium chloride. Adding antimicrobials is not now considered an acceptable approach to the formulation of nebulizer solutions. The solubility of the drug is important since it may impact upon the performance of the solution in a selected nebulizer. Additives may form complexes with the drug. 

The anatomic location of the GI infection influences the selection of the antimicrobial agent and the route of... 

The initial selection of an antimicrobial agent for the treatment of UTI is primarily based on the severity of the presenting signs and symptoms, the site of infection, and whether the infection is determined to be complicated or uncomplicated. 

Weiss MJ, Wong JR, Ha CS, et al. Dequalinium, a topical antimicrobial agent, displays anticarcinoma activity based on selective mitochondrial accumulation. Proc Natl Acad Sci USA 1987 84(15) 5444-5448. 

These are pyrimidine derivatives and are effective because of differences in susceptibility between the enzymes in humans and in the infective organism. Anticancer agents based on folic acid, e.g. methotrexate, inhibit dihydrofolate reductase, but they are less selective than the antimicrobial agents and rely on a stronger binding to the enzyme than the natural substrate has. They also block pyrimidine biosynthesis. Methotrexate treatment is potentially lethal to the patient, and is usually followed by rescue with folinic acid (A -formyl-tetrahydrofolic acid) to counteract the folate-antagonist action. The rationale is that folinic acid rescues normal cells more effectively than it does tumour cells. 

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