Chloramphenicol

·        Chemistry.

·        Pharmacokinetics.

·        Adverse effects.

Chemistry

1.       Originally isolated from Streptomyces venezuelae.

2.       Esters of chloramphenicol:

a.       Chloramphenicol palmitrate: for oral use as a suspension; tasteless.

b.       Chloramphenicol succinate: water soluble, suitable for i.v. use.

3.       Mechanism of action:

a.       Inhibits protein synthesis in bacteria by binding reversible to 50S subunit.

b.    Also inhibits mitochondrial protein synthesis in mammalian cells.

4.       Generally a bacteriostatic drug but may be bactericidal against:

a.       Haemophilus influenzae.

b.       Streptococcus pneumoniae.

c.       Neisseria meningitidis.

5.       Spectrum of activity:

a.       Broad spectrum against a wide range of organisms including Salmonella typhi, anaerobes and rickettsiae.

b.       Active against both anaerobic cocci and bacilli including Bacteroides fragilis.

Pharmacokinetics

1.    Half-life: 5h in adults.

2.    Oral preparations of chloramphenicol are well absorbed, but absorption of chloramphenicol succinate when given i.m. is unreliable.

3.    Both esters have no antimicrobial activity but is hydrolyzed to chloramphenicol.

4.       Metabolized mainly in the liver to chloramphenicol glucuronide which has no antimicrobial activity.

5.    5 – 10% of chloramphenicol is excreted unchanged in the urine.

6.       Penetrates well into most tissues and fluids such as synovial, pleural, peritoneal, CSF, breast milk, and aqueous humor.

Adverse effects

1.    Bone marrow depression:

a.       Dose-dependent, reversible depression of erythrocyte, platelet and leucocyte formation that occurs early in treatment.

b.       Idiosyncratic, non-dose-related, and usually fatal aplastic anaemia which tends to develop during, or even weeks after, prolonged treatment.

2.    Gray baby syndrome:

a.    A potentially fatal reaction occurring in neonates and premature babies exposed to high dosage of chloramphenicol.

b.    May present with cyanotic grey skin, vomiting, abdominal distention and circulatory collapse.

c.       Caused by high chloramphenicol plasma concentration due to failure of the liver to conjugate, and of the kidney to excrete the drug.

3.       Optic and peripheral neuritis occur with prolonged use but are uncommon.

4.       Gastrointestinal upset.

Therapeutic indications

1.    The use of chloramphenicol is limited by its potential to cause aplastic anaemia and it is now only used in special circumstances.

2.       Bacterial meningitis:

a.       Initiating treatment of bacterial meningitis until the causal organism is identified: chloramphenicol + benzylpenicillin.

b.       When the organism is Haemophilus influenzae, type B, chloramphenicol should be continued and the benzylpenicillin stopped.

3.       Initial empirical treatment of brain abscess: chloramphenicol + penicillin.

4.       Chloramphenicol may be used for salmonella infections but ciprofloxacin is preferred.

5.       Topical administration is effective for bacterial conjunctivitis.