Tetracycline antimicrobial activity

Tetracyclines are produced by various Streptomyces strains and are extensively applied in human and veterinary medicine. They display a broad spectrum of antimicrobial activity in combination with low toxicity and can be applied orally. The most commonly prescribed tetracycline drugs are tetracycline itself and oxytetracycline, an oxygenated derivative, which are directly isolated from fermentation liquors, and doxycycline whose partial synthesis from oxy-... 

In 1939 the isolation of a mixture of microbial products named tyrotbricin from a soil bacillus was described. Further investigation showed this material to be a mixture of gramicidin and tyrocidine. In rapid succession the isolation of actinomycin (1940), streptothricin (1942), streptomycin (1943), and neomycin (1949), produced by Streptomjces were reported and in 1942 the word antibiotic was introduced. Chloramphenicol, the first of the so-called broad spectmm antibiotics having a wide range of antimicrobial activity, was discovered in 1947. Aureomycin, the first member of the commercially important tetracycline antibiotics, was discovered in 1948. 

Pharmacology The tetracyclines are bacteriostatic. They exert their antimicrobial effect by inhibition of protein synthesis. Tetracyclines are active against a wide range of gram-positive and gram-negative organisms. 

Tetracyclines are a family of antibiotics which display a characteristic 4-fused-core ring structure (Figure 1.16). They exhibit broad antimicrobial activity and induce their effect by inhibiting protein synthesis in sensitive microorganisms. Chlortetracycline was the first member of this family to be discovered (in 1948). Penicillin G and streptomycin were the only antibiotics in use at that time, and chlortetracycline was the first antibiotic employed therapeutically that retained its antimicrobial properties upon oral administration. Since then, a number of additional tetracyclines have been discovered (all produced by various strains of Streptomyces), and a variety of semi-synthetic derivatives have also been prepared (Table 1.18). 

Although all tetracyclines have a similar mechanism of action, they have different chemical structures and are produced by different species of Streptomyces. In addition, structural analogues of these compounds have been synthesized to improve pharmacokinetic properties and antimicrobial activity. While several biological processes in the bacterial cells are modified by the tetracyclines, their primary mode of action is inhibition of protein synthesis. Tetracyclines bind to the SOS ribosome and thereby prevent the binding of aminoacyl transfer RNA (tRNA) to the A site (acceptor site) on the 50S ri-bosomal unit. The tetracyclines affect both eukaryotic and prokaryotic cells but are selectively toxic for bacteria, because they readily penetrate microbial membranes and accumulate in the cytoplasm through an energy-dependent tetracycline transport system that is absent from mammalian cells. 

The answer is b. (Hardman, p 1128.) Tetracycline is one of the drugs of choice in the treatment of Rickettsia, Mycoplasma, and Chlamydia infections. The antibiotics that act by inhibiting cell-wall synthesis have no effect on Mycoplasma because the organism does not possess a cell wall penicillin G, vancomycin, and bacitracin will be ineffective. Gentamicin has little or no antimicrobial activity with these organisms. 

The microorganism used for tetracycline are Staphylococcus aureus NCTC 6751 and Staphylococcus aureus ATCC 6538 P. The buffer solution with a pH of 4.5 and the incubation temperature between 35 - 37 °C are used (90, 91). Additives in TC formulations can influence the results obtained by microbiological methods (92). Comparison of the microbiological results has been made with those obtained through other methods (93, 94). Effects of certain tablet-formula-tion-additives such as starch, bentonite, veegum F, talc, liquid paraffin, stearic acid etc. on the antimicrobial activity of TC-HC1 has been investigated (95). 

Tetracyclines have a broad range of antimicrobial activity and differences between the individual members are in general small. 

Polyoxyethylene stearates are unstable in hot alkaline solutions owing to hydrolysis, and will also saponify with strong acids or bases. Discoloration or precipitation can occur with salicylates, phenolic substances, iodine salts, and salts of bismuth, silver, and tannins.Complex formation with preservatives may also occur. The antimicrobial activity of some materials such as bacitracin, chloramphenicol, phenoxymethylpenicillin, sodium penicillin, and tetracycline may be reduced in the presence of polyoxyethylene stearate concentrations greater than 5% w/w. ... 

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... 

Various parts of M. oleifera are identified for innumerable pharmacological properties viz. antimicrobial activity (12, 134). The juice from the leaves and stem bark of M. oleifera inhibit Staphylococcus aureus but not Escherichia coli (50). The fresh leaf juice inhibits the growth of pathogenic Pseudomonas aeruginosa and Staphylococcus aureus (21, 143). The bark extract possesses anti-fungal and anti-tubercular activity (50). Niaziridin rich fraction of M. oleifera pods enhances the bioactivity of commonly used antibiotics such as rifampicin, tetracycline and ampicillin against gram(+) and (-) bacteria (37). 

Tetracyclines including semi-synthetic derivatives like doxycycline and minocycline are offering a wide range of antimicrobial activity against Gram-positive, Gramnegative bacteria and even some protozoa infections. 

Asker, A., M. el-Nakeeb, M. Motawi, and N. el-Gindy. 1973. Effect of certain tablet formulation factors on the antimicrobial activity of tetracycline hydrochloride and chloramphenicol. 3. Effect of lubricants. Pharmazie. 28 476M78. 

Robinson expressed this skepticism (45) when he wrote in 1953 .. . indeed one of the disappointments in antibiotic work is that it seems impossible to modify the molecule without reducing or eliminating its antimicrobial activity. . . The discoveries early in the 1950 s of tetracycline and phenoxymethylpenicillin established beyond doubt, however, that modification of antibiotics by chemical or biosynthetic means could yield superior drugs. 

The high level of antimicrobial activity of tetracycline established earlier reveal that the substitutions on the C-5 and C-7 were not an essential requirement. 

Oleandomycin, a 14-membered ring macrolide antibiotic, was isolated in 1956 from fermentation broths of Streptomyces antibioticus [360]. Some years later, oleandomycin was assigned the structure 340 on the basis of its chemical degradation [361]. Oleandomycin is effective, but less potently, against the same spectrum of bacteria as erythromycin, namely Gram-positive bacteria such as staphylococci, streptococci, and pneumococci. The antimicrobial activity of oleandomycin, when combined with tetracycline, is potentiated. In fact, in such a combination it is sold as an antibacterial agent for upper and lower respiratory tract infection. 

Structural modifications in rings C and D have been used to produce a range of semisyn-thetic tetracyclines with altered antimicrobial activities (49), The aromatic ring D is par-... 

Antimicrobial activity was also investigated for the positive control, tetracycline against the pathogens. It s found that the area of the zone of inhibition, AZOI in several instances is less than that induced by the n-CeHu and CH3CH2OH extract of Solanum melongena, Moringa oleifera, Brassica rapa chinensis andArtocarpus altilis. 

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