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Chloramphenicol has a simple nitrobenzene ring structure that can now be mass produced by chemical synthesis. It influences protein synthesis by binding to the 50S ribosomal subunit and blocking the action of peptidyl transferase, which prevents formation of the peptide bond essential for extension of the peptide chain. Its action is reversible in most susceptible species; thus, it is bacteriostatic. It has little effect on eukaryotic ribosomes, which explains its selective toxicity.
A broad-spectrum antibiotic, chloramphenicol, like tetracycline, has a wide range of activity against both aerobic and anaerobic species (see Table 13 – 1). Chloramphenicol is readily adsorbed from the upper gastrointestinal tract and diffuses readily into most body compartments, including the cerebrospinal fluid. It also permeates readily into mam-malian cells and is active against obligate intracellular pathogens such as Rickettsia and Chlamydia.
The major drawback to this inexpensive, broad-spectrum antimicrobial with almost ideal pharmacologic features is a rare but serious toxicity. Between 1 in 50,000 and 1 in 200,000 patients treated with even low doses of chloramphenicol have an idiosyncratic reaction that results in aplastic anemia. The condition is irreversible and, before the advent of bone marrow transplantation, it was universally fatal. In high doses, chloramphenicol also causes a reversible depression of the bone marrow and, in neonates, abdominal, circu-latory, and respiratory dysfunction. The inability of the immature infant liver to conjugate and excrete chloramphenicol aggravates this latter condition.
Chloramphenicol use is now restricted to treatment of rickettsial or ehrlichial infec-tions in which tetracyclines cannot be used because of hypersensitivity or pregnancy. Its central nervous system (CNS) penetration and activity against anaerobes continue to lendsupport to its use in brain abscess. In some developing countries,chloramphenicol use is more extensive because of its low cost and proven efficacy in diseases such as typhoid fever and bacterial meningitis.
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