indication

Used in treatment of cholera, as it destroys the vibrios and decreases the diarrhea. It is effective against tetracycline-resistant vibrios. It is also used in eye drops or ointment to treat bacterial conjunctivitis.

pharmacology

Chloramphenicol is a broad-spectrum antibiotic that was derived from the bacterium Streptomyces venezuelae and is now produced synthetically. Chloramphenicol is effective against a wide variety of microorganisms, but due to serious side-effects (e.g., damage to the bone marrow, including aplastic anemia) in humans, it is usually reserved for the treatment of serious and life-threatening infections (e.g., typhoid fever). Chloramphenicol is bacteriostatic but may be bactericidal in high concentrations or when used against highly susceptible organisms. Chloramphenicol stops bacterial growth by binding to the bacterial ribosome (blocking peptidyl transferase) and inhibiting protein synthesis.

mechanism of action

Chloramphenicol is lipid-soluble, allowing it to diffuse through the bacterial cell membrane. It then reversibly binds to the L16 protein of the 50S subunit of bacterial ribosomes, where transfer of amino acids to growing peptide chains is prevented (perhaps by suppression of peptidyl transferase activity), thus inhibiting peptide bond formation and subsequent protein synthesis.

toxicity

Oral, mouse: LD₅₀ = 1500 mg/kg; Oral, rat: LD₅₀ = 2500 mg/kg. Toxic reactions including fatalities have occurred in the premature and newborn; the signs and symptoms associated with these reactions have been referred to as the gray syndrome. Symptoms include (in order of appearance) abdominal distension with or without emesis, progressive pallid cyanosis, vasomotor collapse frequently accompanied by irregular respiration, and death within a few hours of onset of these symptoms.

biotransformation

Hepatic, with 90% conjugated to inactive glucuronide.

absorption

Rapidly and completely absorbed from gastrointestinal tract following oral administration (bioavailability 80%). Well absorbed following intramuscular administration (bioavailability 70%). Intraocular and some systemic absorption also occurs after topical application to the eye.

half life

Half-life in adults with normal hepatic and renal function is 1.5 - 3.5 hours. In patients with impaired renal function half-life is 3 - 4 hours. In patients with severely impaired hepatic function half-life is 4.6 - 11.6 hours. Half-life in children 1 month to 16 years old is 3 - 6.5 hours, while half-life in infants 1 to 2 days old is 24 hours or longer and is highly variable, especially in low birth-weight infants.

drug interactions

Acetohexamide: Chloramphenicol may increase the effect of sulfonylurea, acetohexamide.

Butalbital: Barbiturates such as butalbital may increase the metabolism of Chloramphenicol. Chloramphenicol may decrease the metabolism of Barbiturates. Monitor for decreased serum concentrations/therapeutic effects of chloramphenicol if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. In addition, monitor for increased effects of barbiturates if chloramphenicol is initiated/dose increased, or decreased effects if chloramphenicol is discontinued/dose decreased.

Chlorpropamide: Chloramphenicol may increase the effect of sulfonylurea, chlorpropamide.

Cyclosporine: Chloramphenicol may increase the effect of cyclosporine.

Ethotoin: Increases phenytoin, modifies chloramphenicol

Fosphenytoin: Increases phenytoin, modifies chloramphenicol

Gliclazide: Chloramphenicol may increase the effect of sulfonylurea, gliclazide.

Glipizide: Chloramphenicol may increase the effect of sulfonylurea, glipizide.

Glisoxepide: Chloramphenicol may increase the effect of sulfonylurea, glisoxepide.

Glyburide: Chloramphenicol may increase the effect of sulfonylurea, glibenclamide.

Glycodiazine: Chloramphenicol may increase the effect of sulfonylurea, glycodiazine.

Mephenytoin: Increases phenytoin, modifies chloramphenicol

Phenytoin: Increases phenytoin, modifies chloramphenicol

Rifampin: Rifampin decreases the effect of chloramphenicol

Tacrolimus: Chloramphenicol may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Chloramphenicol therapy is initiated, discontinued or altered.

Thiopental: Chloramphenicol may increase the serum concentration of Thiopental by decreasing Thiopental metabolism. Thiopental may decrease the serum concentration of Chloramphenicol by increasing Chloramphenicol metabolism. Monitor for changes in therapeutic effects of both agents if concomitant therapy is initiated, discontinued or doses are adjusted.

Tolazamide: Chloramphenicol may increase the effect of sulfonylurea, tolazamide.

Tolbutamide: Chloramphenicol may increase the effect of sulfonylurea, tolbutamide.