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Chapter 24 : Tetracyclines
The use of tetracyclines is less widespread now than in the past due to the emergence of antibacterial resistance to these antibiotics and the discovery of more effective and selective molecules. The physicochemical properties of the tetracyclines may be modified by minimal structural variations. The antibacterial spectrum and activity of the tetracyclines include numerous gram-positive and gram-negative bacteria, anaerobes, rickettsiae, mycoplasmas, chlamydiae, Helicobacter pylori, and spirochetes. In the case of gram-negative bacteria, the first obstacle to be overcome is the bacterial outer membrane. Tetracyclines probably penetrate the periplasmic space via transmembrane proteins forming hydrophilic channels. The therapeutic use of tetracyclines is increasingly undermined by the frequent emergence of resistance. Hypersensitivity reactions to tetracyclines are rare but may include anaphylactic shock, urticaria, periorbicular edema, rashes, and morbilliform rashes. The hepatotoxicity of the tetracyclines, first described with chlortetracycline, is now known for all tetracyclines. The results of experimental studies in animals are contradictory with respect to the teratogenicity of tetracyclines: some authors have reported inhibited growth and skeletal deformities in the rat and chicken, whereas according to other authors this risk is nonexistent. Several authors have reported yellow or brown discoloration of the milk teeth in children born to mothers treated with tetracyclines (tetracycline and oxytetracycline) during the second and particularly the third trimesters of pregnancy. Majority of tetracyclines can cause a cerebral pseudotumor syndrome, characterized by a benign increase in intracranial pressure in children and adults. Tetracyclines are used in cases of nonspecific urethritis and urethral syndrome.