Antibiotics bacterial strains resistant

With a constantly growing number of pathogenic bacterial strains resistant to the known antibiotics, the demand for novel antibiotics or, more generally speaking, therapeutic agents is evident. Because many NRPS products already have such activities and their chemical and structural diversity is so huge, efforts have been made to use NRPSs to broaden the known spectrum of therapeutics. In this section, the possibilities of using NRPS machineries or parts of them to produce new bioactive compounds are addressed. 

Vancomycin is most often the antibiotic of last resort for the treatment of resistant bacterial strains, however, bacterial strains resistant to vancomycin are now emerging [19]. The health threat posed by these strains has led to intense research into both the mechanism by which resistance develops and the development of pharmaceutical antibacterial agents with novel modes of action. 

Many in vitro studies have firmly established a synergism between sulbactam and various P-lactam antibiotics including piperacillin, amdinocillin, ampicillin, and penicillin G. These studies included bacterial strains resistant to ampicillin or penicillin G alone, which became sensitive upon addition of sulbactam. Carbenicillin-resistant Pseudomonas, however, was not potentiated. 

Employed as a sodium salt, fusidic acid (Fig. 5.14B) is achve against many types of Gram-positive bacteria, especially staphylococci, although streptococci are relatively resistant. It is employed in the treatment of staphylococcal infections, including strains resistant to other antibiotics. However, bacterial resistance may occur in vitro and in vivo. 

For highly potent APIs, profound effects can occur at low ng levels, the adverse effect of ethynylestradiol on fish populations is one example [107]. Another example is the development of resistant bacterial strains induced by the release of antibiotics into the environment [112, 113]. Dome et al. [114] concluded that fluoxetine, ibuprofen, diclofenac, propranolol and metoprolol exhibit relatively high acute toxicity to aquatic species. In addition, due to the inherent properties of these chemicals, pharmacodynamic effects were observed in the heart rate of Daphnia magna for the (3-blockers propranolol and metoprolol. 

In human medicine, selection pressure is at its most intense in hospitals, where antibiotics are extensively used. The major cause of problems of antimicrobial resistance in humans arises from overuse of antimicrobials at therapeutic levels in humans. It is generally accepted that drug resistance that develops in a bacterium as a result of mutation is only of importance within the individual host and a single bacterial strain. Because the determinant is chromosomal, the resistance cannot be transferred between different bacterial species and genera. In addition, the mutationally resistant microorganism is not usually as viable as the wild ones hence once the selective antibiotic is removed from the environment, the proportions of the mutant decrease. If exposure to the antibiotic continues, however, the mutants can become life-threatening to the patient. It should be understood that the antibiotic does not induce the mutation. The mutant simply takes advantage of its fortuitous spontaneous appearance to flourish in the presence of a selected antibiotic. 

R-plasmid-mediated resistance is almost invariably associated with crossresistance to a number of related and unrelated antibiotics. The reasons for the association lie in the resistance mechanism to related compounds that have been coded, the usual presence of more than one R determinant in the same plasmid, and the frequent coexistence of several different plasmids in the same bacterial cell. As a result, use of any antibiotic can lead to development of resistance to itself and to other related and unrelated antibiotics. If, for example, a plasmid is encoded for resistance to ampicillin, tetracycline, sulfonamide, and streptomycin, exposure to any of these antibiotics results in resistance to all the others, whereas the use of a -lactamase-containing strain results in resistance to other members of this group. 

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