Resistance is due to deactivation of the drug by acetylation of the hydroxyl group, amidase hydrolysis of the amide group, or reduction of the nitro group. Enzymes coding for these reactions are normally found in some organisms rending them uniformly resistant. Plasmids coding for acetyltransferase may be transferred by transduction. Plasmids exist that code for multiple drug resistance, e.g., to chloramphenicol, tetracycline, and streptomycin. In the absence of a plasmid, resistance develops slowly.
Selection pressure increases the frequency of plasmids coding for resistance.
In pigs fed 20 ppm of chloramphenicol for some time, sensitive coliforms were replaced by resistant ones. Because of the potential for development of hypersensitivity, chloramphenicol should be used in topical applications sparingly, paying special attention to protecting the person administering the drug. Free chloramphenicol is rapidly absorbed after IV and PO administration, but is slowly absorbed from IM sites. Tablets should be from reputable manufacturers with good quality control. Intramuscular injections of chloramphenicol are not recommended.