Resistance antibacterials

Uses Epoxy resin curing agent (composite aircraft bodies/components) hardener for adhesives, PWB laminates, prepregs, composites, powd. coatings exc. high temp, and chem. resist. antibacterial in treatment of dermatitis herpetiformis leprosy treatment drug veterinary medicine... 

Oxazolidinones are useful as chiral auxiliaries in asymmetric synthesis, and precursors of nafurally occurring amino alcohols and amino acids. Recently, some oxazolidinone derivatives such as DUP-105, DUP-721, and line-zolid (Zyvox) have attracted much interest as monodrug- or multidrug-resistant antibacterial agents [156]. General method of preparation to oxazolidinones include the reactions of 1,2-amino alcohols and phosgene or ifs derivatives... 

Fu GD, Yao F, li Z, Li X (2008) Solvent-resistant antibacterial mictofibers of self-quaternized block copolymers from atom transfer radictil polymerization and electrospinning. J Mater Chem 18(8) 859 7. doi 10.1039/b716127a... 

Development of Resistance. One of the principal disadvantages of sulfonamide therapy is the emergence of dmg-resistant strains of bacteria. Resistance develops by several mechanisms overproduction of PABA (38) altered permeabiUty of the organisms to sulfonamides (39) and reduced affinity of dihydropteroate synthetase for sulfonamides while the affinity for PABA is retained (40). Sulfonamides also show cross-resistance to other sulfonamides but not to other antibacterials. In plasmodia, resistance may occur by means of a bypass mechanism in which the organisms can use preformed foHc acid (41). 

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... 

The development of new antibiotics to combat resistance, and to provide easier oral administration and improved pharmacokinetics has been successful through synthetic modifications. This approach has been particularly rewarding in the area of P-lactams. The commercial importance of the P-lactams is evident from Table 3 which gives the market share of antibacterials. Fully 62% of the 1989 world antibacterial market belonged to the cephalosporin and penicillin P-lactams (20). 

Tolypomycin Y (48) shows strong antibacterial activity against gram-positive bacteria and Neisseriagonorrheae. When adininistered by subcutaneous, intraperitoneal, and intravenous routes, tolypomycin Y is effective in mice infected with Staphylococcus aureus Streptococcuspyrogenes and Diplococcuspneumoniae. Cross-resistance is observed with rifampicia but not with other antibiotics. Resistance to tolypomycin Y develops rapidly. The bioactivity of tolypomycin R... 

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). 

Other specific discovery assays have been used such as differential inhibition of a vancomycin resistant S. aureus strain and its susceptible parent, and an assay based on antagonism of the antibacterial activity by N,A/-diacetyl-L-Lys-D-Ala-D-Ala [24570-39-6] a tripeptide analogue of the dalbaheptides receptor. AppHcation of this latter test to 1936 cultures (90) led to the isolation of 42 dalbaheptides, six of which, including kibdelin (Table 3), parvodicin (Table 3), and actinoidin A2 (68) were novel. A colorimetric assay based on competition between horseradish peroxidase bound teicoplanin and the... 

A variety of chemical products and fabrics are reputed to be antibacterial and to prevent odors and the spread of infection (170). One such finish is based on an organosiUcon quaternary ammonium chloride compound (171). Chemical finishing of cotton has also been directed toward improving soil release (172,173), antistatic treatments (174), and rot resistance (175,176). 

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). 

The antibacterial effectiveness of penicillins cephalospotins and other P-lactam antibiotics depends upon selective acylation and consequentiy, iaactivation, of transpeptidases involved ia bacterial ceU wall synthesis. This acylating ability is a result of the reactivity of the P-lactam ring (1). Bacteria that are resistant to P-lactam antibiotics often produce enzymes called P-lactamases that inactivate the antibiotics by cataly2ing the hydrolytic opening of the P-lactam ring to give products (2) devoid of antibacterial activity. 

Clavulanic acid has only weak antibacterial activity, but is a potent irreversible inhibitor for many clinically important P-lactamases (10—14,57,58) including penases, and Richmond-Sykes types 11, 111, IV, V, VI ([Bacteroides). Type I Cephases are poorly inhibited. Clavulanic acid synergizes the activity of many penicillins and cephalosporins against resistant strains. The chemistry (59—63), microbiology (64,65), stmcture activity relationships (10,13,60—62,66), biosynthesis (67—69), and mechanism of action (6,26,27,67) have been reviewed. 

Resistance to Tetracyclines. The tetracyclines stiU provide inexpensive and effective treatment for several microbial infections, but the emergence of acquired resistance to this class of antibiotic has limited their clinical usehilness. Studies to define the molecular basis of resistance are underway so that derivatives having improved antibacterial spectra and less susceptibiUty to bacterial resistance may be developed. Tetracyclines are antibiotics of choice for relatively few human infections encountered in daily clinical practice (104), largely as a result of the emergence of acquired tetracycline-resistance among clinically important bacteria (88,105,106). Acquired resistance occurs when resistant strains emerge from previously sensitive bacterial populations by acquisition of resistance genes which usually reside in plasmids and/or transposons (88,106,107). Furthermore, resistance deterrninants contained in transposons spread to, and become estabUshed in, diverse bacterial species (106). 

Several promising antibacterial compounds are available and may be considered for use in U.S. aquaculture. In addition to sarafloxacin, other quinolones, flumequine and oxolinic acid, are already registered in Europe. However, resistance to both of these compounds developed in bacteria in just a few years (20). Enrofloxacin, [95106-60-6], C22H22FN2O2, a quinolone product of Bayer A.G. (Germany), is also a candidate for aquaculture registration in Europe and may be considered for registration in the United States. 

Norfloxacin (1, R = C2H5, R = H), a typical example, exhibits broad-spectrum activity and is useful in the treatment of upper respiratory tract and urinary infections [7] Lomefloxacin (2), a very recent introduction, is a third-generation product that, given once daily, is especially useful against pathogens resistant to cephalosponns, penicillins, and aminoglycosides [4] Floxacillin (J) is a stable, orally active antibacterial with improved activity over thenonfluonnated product (cloxacillin) [5]... 

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