Chloramphenicol

Chloramphenicol
CHLORAMPHENICOL SODIUM SUCCINATE® FDA Package Insert
Description
Clinical Pharmacology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Dosage and Administration
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]

Overview

Chloramphenicol is a bacteriostatic antimicrobial originally derived from the bacterium Streptomyces venezuelae, isolated by David Gottlieb, and introduced into clinical practice in 1949.

It was the first antibiotic to be manufactured synthetically on a large scale. Chloramphenicol is effective against a wide variety of microorganisms; it is still very widely used in low income countries because it is exceedingly cheap, but has fallen out of favour in the West due to a very rare but very serious side effect: aplastic anemia.

In the West, the main use of chloramphenicol is in eye drops or ointment for bacterial conjunctivitis.

Thiamphenicol is a related compound with a similar spectrum of activity that is available in Italy and China for human use, and has never been associated with aplastic anaemia. Thiamphenicol is available in the U.S. and Europe as a veterinary antibiotic, and is not approved for use in humans.

Mechanism and resistance

Chloramphenicol is bacteriostatic (that is, it stops bacterial growth). It functions by inhibiting peptidyl transferase, preventing peptide bond formation. While chloramphenicol and the macrolide class of antibiotics both interact with the 50S ribosomal subunit, chloramphenicol is not a macrolide. Furthermore, their mechanisms are slightly different. While chloramphenicol directly interferes with substrate binding, macrolides sterically block the progression of the growing peptide.

There are three mechanisms of resistance to chloramphenicol: reduced membrane permeability, mutation of the 50S ribosomal subunit and elaboration of chloramphenicol acetyltransferase. It is easy to select for reduced membrane permability to chloramphenicol in vitro by serial passage of bacteria, and this is the most common mechanism of low-level chloramphenicol resistance. High level resistance is conferred by the cat-gene; this gene codes for an enzyme called chloramphenicol acetyltransferase which inactivates chloramphenicol by covalently linking one or two acetyl groups, derived from acetyl-S-coenzyme A, to the hydroxyl groups on the chloramphenicol molecule. The acetylation prevents chloramphenicol from binding to the ribosome. Resistance-conferring mutations of the 50S ribosomal subunit are rare.

Chloramphenicol resistance may be carried on a plasmid that also codes for resistance to other drugs. One example is the ACCoT plasmid (A=ampicillin, C=chloramphenicol, Co=co-trimoxazole, T=tetracycline) which mediates multi-drug resistance in typhoid (also called R factors).

US Brand Names

CHLORAMPHENICOL® (DISCONTINUED)

FDA Package Insert

Description | Clinical Pharmacology | Indications and Usage | Contraindications | Warnings and Precautions | Adverse Reactions | Dosage and Administration | How Supplied | Labels and Packages

References

http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=aed29594-211d-49ef-813f-131975a8d0e3