Chloramphenicol

Common indications

• Bacterial conjunctivitis using eye drops or ointment.
• Otitis externa using ear drops.
• Due to its toxicity, systemic (oral or IV) chloramphenicol is rarely used. In the UK, it is restricted to the treatment of life-threatening infection, and only where other, safer antibiotic classes cannot be used due to allergy or bacterial resistance. This may include occasional cases of epiglottitis (Haemophilus influenzae) and typhoid fever (Salmonella spp.).

Spectrum of activity

• Chloramphenicol has broad activity against many Gram-positive, Gram-negative, aerobic and anaerobic organisms.

Mechanisms of action

• Chloramphenicol binds to bacterial ribosomes, inhibiting protein synthesis. 
• It is thus bacteriostatic (stopping bacterial growth), which helps the immune system to clear microorganisms. 
• In high concentrations and with highly susceptible organisms it can be bactericidal (killing). 
• The most common mechanism of bacterial resistance to chloramphenicol is production of acetyltransferase enzymes that directly inactivate the drug. 
• Other mechanisms include target modification, decreased membrane permeability and increased expression of efflux pumps. 
• Bacteria share antibiotic resistance genes by ‘horizontal transfer’ in plasmids. 
• However, many bacteria remain sensitive to chloramphenicol, probably due to its restricted use over recent decades.

Important adverse effects

• The most common adverse effects to topical administration are transient stinging, burning and itching when applied. 
• Systemic administration, which is rare in developed-world practice, carries a significant risk of bone marrow toxicity. This takes two distinct forms: 
• (i) Dose-related bone marrow suppression is more likely with high-dose therapy, or when the drug accumulates due to impaired hepatic metabolism. It occurs during treatment and is reversed on drug withdrawal. 
• (ii) Aplastic anaemia is idiosyncratic; it has an unpredictable relationship with dose and may be delayed. It is a rare but life-threatening reaction to systemic therapy only.
• Grey baby syndrome is circulatory collapse occurring in exposed neonates who are unable to metabolise and excrete the drug.
• Optic and peripheral neuritis may occur with prolonged systemic administration.

Warnings

• It is contraindicated in people with previous hypersensitivity reactions to chloramphenicol, and a personal or family history of bone marrow disorders. 
• Systemic chloramphenicol is contraindicated in the third trimester of pregnancy, breastfeeding and in children <2 years because of the risk of grey baby syndrome; topical preparations should also be avoided unless essential. 
• Chloramphenicol is metabolised by the liver, and so dose adjustment and monitoring are required in hepatic impairment.

Important interactions

• Chloramphenicol has no important interactions when administered topically.