Resistance to antibacterial agents

The second general mechanism to cause resistance to antibacterial agents is to prevent the drug from reaching its target site. This is either achieved by altered rates of entry (reduced uptake) or by the active removal of the dtug (active efflux) [4]. 

It must be emphasized that the subject of bacterial resistance to antibacterial agents is a huge one. Consequently, as far as possible, only recent theories and practicalities will be described here, and reviews will be cited frequently, although occasionally some older work will perforce be referred to when necessary. 

It is clear from the preceding sections that bacterial resistance to antibacterial agents, especially antibiotics, is of mounting concern. Increasingly, therefore, attention is being devoted to ways of overcoming this problem. This section will thus consider possible means of counteracting bacterial resistance. 

In general terms, bacterial resistance to antibacterial agents can be considered as being either intrinsic (innate, a natural property) or acquired, for example, by mutation or by the acquisition of a plasmid or transposon (jumping gene) [105]. Resistance to mercury [103, 122-125] and to other cations and anions [103, 122, 123, 125] is well characterized. The mechanisms involved in resistance to some metals, including silver, are summarized in Table 7.1. 

Davies D. 2003. Understanding biofihn resistance to antibacterial agents. Nature Rev Drug Discov 2 114-122. 

Davies, D. (2003). Understanding biofilm resistance to antibacterial agents. Nat. Rev. Drug Discov. 2,114-122. 

Kolwzan B., T. Traczewska, and M. Pawlaczyk-Szipilowa (1991). Examination of resistance of bacteria isolated from drinking water to antibacterial agents. Environmental Protection Engineering 17 53-60. 

The organism is sensitive to physical agents such as heat sterilisation, radiation and cold shock [6,7], and it is therefore its resistance to antimicrobial agents which poses the major problem. The continued use of antibacterial agents will no doubt exacerbate the situation unless more effective agents are discovered. 

Lomefloxacin and quinolone agents in general are known to exert their antibacterial action by antagonism of the enzyme DNA gyrase also known as bacterial topoisomerase II. DNA gyrase has also been shown to play an important role in the mechanism of bacterial resistance to these agents (30). 

Bacteria are known to react differently to antibacterial agents. This is due either to inherent differences, which may be their unique cell envelope composition or proteins not being susceptible or as a result of resistance development, by adaptation exchange of genetic information. For organic acids to be effective as an antibacterial, they must be able to penetrate the cell envelope and attain a sufficiently high concentration at the target site where they will exert antibacterial action (Cloete, 2003). 

Brown MRW, Richards RME (1965) Effect of ethylenediamine tetraacetate on the resistance of pseudomonas aemginosa to antibacterial agents. Nature 207 1391-1393... 

Figure 14.2 Series of events leading to biofihn formation on an implant surface. These events include (a) cell adherence to the implant s surface with the help of a specialized structure on the bacterial cell wall, (b) cell to cell attachment, (c) cell proliferation leading to growth and aggregation, and (d) biofihn maturation and development of resistance against antibacterial agents.

Antibacterial Agents. There is a continuous need for new antibiotics primarily as a result of bacterial resistance. There are two aspects to this phenomenon. Fkst, as the mote common pathogens are contioUed by antibiotics, less common, highly resistant organisms present mote prominent health... 

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). 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

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