Antimicrobial response

Carpenter, S., O Neill, L.A. How important are Toll-like receptors for antimicrobial responses Cell Microbiol 9 (2007) 1891-1901. 

Liu, P.T. et al. (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science, 311, 1770-1773. 

The possibility to combine different reinforcement phases in a polymer matrix was also recently considered in order to obtain multifunctional systems with increased mechanical and thermal properties providing also an antimicrobial response. In a recently accepted paper [160] Fortunati et al. demonstrated the high potential benefits offered by nanotechnology in the development of tailor-made nanobiocomposites with specific applications by the combination of two different synthesized nanostructures inorganic nanoparticles and cellulose nanocrystals in a biodegradable polymer matrix. 

Liu, L, Roberts, A. A., and Ganz, T., By lL-1 signaling, monocyte-derived cells dramatically enhance the epidermal antimicrobial response to hpopolysaccharide, J. Immunol, 170,575,2003. 

GRAYFER L, GARCIA EG, BELOSEVIC M (2010), Comparison of macrophage antimicrobial responses induced by type II interferons of the goldfish Carassius auratus L.) , I Biol Chem, 285,23537-47. 

The antimicrobial activity of this class of compounds was first reported ia 1943 (1) and this finding was described iadependendy four years later (2). After iavestigation of several derivatives, it was concluded that the 5-nitro function was responsible for the observed antimicrobial activity (3). These preliminary findings focused attention on this area of research and as a result, several thousand nitrofurans have been prepared, and thousands of articles have been prepared, and thousands of articles have been pubUshed describiag the extensive efforts ia these areas. 

This wide range of pharmacokinetic properties, along with thek ease of administration, broad spectmm antimicrobial activity, and noninterference with host-defense mechanisms is responsible for thek widespread use five decades after thek discovery. 

Antimicrobial Activity. The elfamycins antimicrobial specificity and lack of toxicity in animals can be explained in view of species-dependent specificity of elfamycin binding to EE-Tu. Inefficient cellular uptake or the presence of a nonresponding EE-Tu were cited as responsible factors for the natural resistance in Halohacterium cutiruhrum (67), Lactobaci//us brevis (68), and in actinomycetes (5,69). The low activity of elfamycins against S. aureus was also attributed to an elfamycin-resistant EE-Tu system (70). However, cross-resistance with other antibacterial agents has not been observed (71). 

The dissociation of hypochlorous acid depends on the pH. The unionized acid is present in greater quantities in acid solution, although in strongly acid solution the reaction with water is reversed and chlorine is Hberated. In alkaline solutions the hypochlorite ion OCL is increasingly Hberated as the pH is increased. The pH is important because unionized hypochlorous acid is largely responsible for the antimicrobial action of chlorine in water. Chlorine compounds are therefore more active in the acid or neutral range. The hypochlorites most commonly employed are sodium hypochlorite [7681-52-9] or calcium hypochlorite [7778-54-3]. 

Povidone—iodine is a brown, water-soluble powder containing approximately 10% iodine. However, the amount of free iodine, which is responsible for the antimicrobial activity, is low in a concentrated solution, but is released as the solution is diluted (41). Concentrated solutions have actually been contaminated with bacteria (42). For use as an antiseptic, povidine—iodine is diluted with water or alcohol to a concentration of 1% iodine. Detergents are added if it is used as a surgical scmb. lodophors are important as broad-spectmm antiseptics for the skin, although they do not have the persistent action of some other antiseptics. They are also used as disinfectants for clinical thermometers that have been used by tuberculous patients, for surface disinfection of tables, etc, and for clean equipment in hospitals, food plants, and dairies, much as chlorine disinfectants are used. 

Metal compounds, particularly compounds of the heavy metals, have a history of importance as antimicrobial agents. Because of regulations regarding economic poisons in the environment they are no longer widely used in this appHcation. Mercury, lead, cadmium, uranium, and other metals have been imphcated in cases of poisoning that resulted in government response. The metals whose compounds have been of primary interest as antimicrobials are mercury, silver, and copper. 

Hammond JN, Leavitt MC, Rudy JJ, Isaacson JS, Hertogs K, Larder BA, Pattick AK (2003) Long-term virological response to capravirine in HIV-infected NNRTI-experienced patients. In 43rd interscience conference on antimicrobial agents and chemotherapy. Chicago, IL, Abstract H-871... 

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. 

Although a few mechanisms have so far been proposed to explain the antimicrobial properties exhibited by proanthocyanidins (e.g., inhibition of extracellular enzymes) [86], Jones et al. [83] postulated that their ability to bind bacterial cell coat polymers and their abihty to inhibit cell-associated proteolysis might be considered responsible for the observed activity (Table 1). Accordingly, despite the formation of complexes with cell coat polymers, proanthocyanidins penetrated to the cell wall in sufficient concentration to react with one or more ultra-structural components and to selectively inhibit cell wall synthesis. Decreased proteolysis in these strains may also reflect a reduction of the export of proteases from the cell in the presence of proanthocyanidins [83]. 

Stream-line antimicrobial therapy based on clinical judgment, patient response, and microbiological data... 

Select empirical antimicrobial therapy based on spectrum-of-activity considerations that provide a measured response proportional to the severity of illness. Provide a rationale for why a measured response in antimicrobial selection is appropriate. 

Identify and apply five major principles of patient education and monitoring response to antimicrobial therapy. 

Bacterial cultures should be obtained prior to antimicrobial therapy in patients with a systemic inflammatory response, risk factors for antimicrobial resistance, or infections where diagnosis or antimicrobial susceptibility is uncertain. 

Patient education, deescalation of antimicrobial therapy based on culture results, monitoring for clinical response and... 

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. 

After selection and initiation of antimicrobial regimen, there are a number of additional patient care and monitoring considerations that should be addressed to improve the likelihood of a successful outcome. Patient education, deescalation of antimicrobial therapy based on culture results, monitoring for clinical response and adverse effects, and appropriate duration of therapy are important. 

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