Sulfonamides antimicrobial activity

In subsequent studies attempting to find a correlation of physicochemical properties and antimicrobial activity, other parameters have been employed, such as Hammett O values, electronic distribution calculated by molecular orbital methods, spectral characteristics, and hydrophobicity constants. No new insight on the role of physiochemical properties of the sulfonamides has resulted. Acid dissociation appears to play a predominant role, since it affects aqueous solubiUty, partition coefficient and transport across membranes, protein binding, tubular secretion, and reabsorption in the kidneys. An exhaustive discussion of these studies has been provided (10). 

Sulfouamides have a broad spectrum of antimicrobial activity, including Staphylococcus aureus, nonenterococcal types of Streptococcus, Listeria monocytogenes, Nocardia, Neisseria, Haemophilius influenzae, enteric Gram-negative types of E. coli, Proteus mirabilis, and a few forms of anaerobic bacteria. Above all, sulfonamides are used for treating uncomplicated infections of the urinary tract, infections caused by Nocardia asteroids, streptococcal pharyngitis, menigococcal diseases, toxoplasmosis, and others. 

Trimethoprim has a broad spectrum of antimicrobial activity. It is 20-100 times more active than sulfamethoxazole with respect to most bacterial forms. Trimethoprim is active with respect to Gram-positive, aerobic bacteria such as Staphylococcus aureus, Staphylococcus epidermidis, and various types of Streptococcus and Listeria monocytogenes. Trimethoprim is inferior to sulfonamides against forms of Nocardia. It is active... 

In 1975, a United States Department of Agricultui e (USDA) survey showed that 5.3% of the 529 carcasses sampled were positive for antibiotic residues (2). Only 17 of the 5301 samples (0.3%) were positive for penicillin, whereas 12 of 728 samples (1.6%) were positive for sulfonamides. Nonspecific antimicrobial activity was found in 154 of the 5301 samples (2.9%) analyzed. 

Even when the pharmacokinetic parameters of a drug are such to suggest that it will reach the site of the infection, local factors can influence its antimicrobial activity. Aminoglycosides are ineffective in hyperosmolar, anaerobic acidic environments, such as the purulent environment of abscesses. Sulfonamides act by replacing para-aminobenzoic acid (PABA) in the folic acid synthetic pathway of bacteria and are ineffective in purulent material and necrotic tissue, which provide alternative sources of PABA. 

The cephalosporins and tetracyclines are commonly used for treatment of UTIs in other species. However, in horses, the cephalosporins are rarely more advantageous than the penicillins or potentiated sulfonamides. However, ceftiofur has broad-spectrum antimicrobial activity and may be indicated when urinary pathogens are resistant to... 

The sulfonamides are nearly completely absorbed from the gastrointestinal tract. Once absorbed they are bound to protein (60% to 90%), mainly to albumin, and are distributed to all tissue. Metabolism is by N-acetylation, with the products having no antimicrobial activity. 

Sulfonamides have wide antimicrobial activity, but their usefulness has diminished as resistant strains have emerged. These drugs are bacteriostatic, and host defenses are essential for eradication of the infection. 

Most drugs in the pyrimidine series fall into four categories the barbiturates, the sulfonamides, the antimicrobials and the antitumour agents. In addition there are innumerable pyrimidines with diverse biological activities, some of which are in use. 

Linear descendants of the antimicrobial sulfonamides, the orally active sulfonylureas continue to be of interest as alternatives to insulin injections in patients with adult-onset diabetes. Tolpyrramide (153) is synthesized from unsymmetrical O-methylurea... 

Among pharmaceuticals, antibiotics have become of special concern in recent years. The reason is that these substances are continuously being introduced into the environment and may spread and maintain bacterial resistance in the different compartments. Sulfonamides are very commonly used antimicrobials in humans but mainly in veterinary medicine, due to their broad spectrum of activity and low cost, being the second most widely used veterinary antibiotic in the EU. Their occurrence has been reported in all kinds of water matrices their high excretion rates (after their intake by humans of livestock) and high water solubility make them very ubiquitous and persistent pollutants in the environment. 

The sulfonamides are a group of organic compounds with chemotherapeutic activity they are antimicrobial agents and not antibiotics. They have a common chemical nucleus that is closely related to PABA, an essential component in the folic acid pathway of nucleic acid synthesis. The sulfonamides are synergistic with the diaminopyrim-idines, which inhibit an essential step further along the folate pathway. The combination of a sulfonamide and a diaminopyrimidine is advantageous because it is relatively non-toxic to mammalian cells (less sulfonamide is administered) and is less likely to select for resistant bacteria. Only these so-called potentiated sulfonamides are used in equine medicine. These drugs are formulated in a ratio of one part diaminopyrimidine to five parts sulfonamide, but the optimal antimicrobial ratio at the tissue level is 1 20, which is achieved because the diaminopyrimidines are excreted more rapidly than the sulfonamides. 

The gastrointestinal tract is a frequent site for adverse effects of antimicrobial drugs, primarily because of disruption of normal intestinal microbial populations and proliferation of enteropatho-gens. Diarrhea, often with accompanying signs of endotoxemia, is the usual clinical manifestation. Antimicrobial agents known to be, or implicated in being, associated with antimicrobial-induced diarrhea include penicillin, ceftiofur, lincomycin, tetracycline, erythromycin and the potentiated sulfonamides. Erythromycin can also promote diarrhea via its motilide activity. 

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