Living Textbook MC610

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Lincomycins

They were first isolated in 1962 from Streptomyces sp., and resemble Macrolides' mechanism of action and spectrum (they are more active against anaerobes). Their binding site on the ribosomes overlap, and thus cross-resistance is frequently seen (MLS group resistance).

They contain a weakly basic Pyrollidene with a pKa of 7.6 and an unusual eight carbon sugar, Thiomethyl aminooctoside, connected by an amide bond. They are water-soluble drugs, that are orally active (usually administered as the HCl salt) and are widely distributed to different body tissues. They are metabolized by N-demethylation, which yields a biologically active metabolite.

Linocmycin is the prototype of this class of agents. Clindamycin was introduced in 1970 and touted to be a superior agent due to the chlorination that increases lipophilicity and thus shows better absorption and penetration into bacterial cells. It also showed an extended spectrum that included some protozoa. It is administered as the Palmitate ester for oral dosage forms and Phosphate ester for topical and parenteral forms. The ester is formed with a hydroxyl group on the sugar molecule.

They have low toxicity, but Clindamycin has been connected to high incidences of pseudomembranous colitis that arises due to toxins produced by an opportunistic agent, Clostridium difficile that can damage the intestinal lining and in some cases is fatal. Thus it is reserved for serious anaerobic infections and topical use in acne. The latter application is prefered to the use of Tetracyclines due to the colorless nature of Clindamycin.