Chloramphenicol is a broad-spectrum antibiotic produced by Streptomyces venezuele that was introduced in 1948. It works by binding to the 50s ribosomal subunit and inhibiting protein synthesis in bacteria. However, it can also interfere with mitochondrial protein synthesis in mammalian cells, causing serious and potentially fatal blood disorders. For this reason, chloramphenicol is now reserved for life-threatening infections like meningitis or rickettsial infections when safer alternatives cannot be used due to resistance or allergies. While effective against a wide range of bacteria, chloramphenicol's use is limited by its risk of toxicities like aplastic anemia and gray baby syndrome in neonates.

1. Chloramphenicol
DR. J.N. CHATURVEDI
ASSOC. PROF. (DESIG.), PHARMACOLOGY
S.S. MEDICAL COLLEGE, REWA (M.P.)

2. Chloramphenicol- Introduction
 Chloramphenicol, an antibiotic produced by Streptomyces venezuele,
was introduced into clinical practice in 1948.
 With the drug’s wide use, it became evident that chloramphenicol
could cause serious and fatal blood dyscrasias.
For this reason, chloramphenicol is now reserved for:
life-threatening infections (e.g., meningitis, rickettsial infections) in
patients who cannot take safer alternatives because of resistance or
allergies

3. Chloramphenicol- Mechanism of action
Penetrates bacterial cell by facilitated diffusion
Binds to 50s ribosomal subunit at peptidyltansferase site
Prevents binding of Aminoacyl-tRNA to A-site of 50s subunit
Inhibition of peptide bond formation
Protein synthesis inhibition
Chloramphenicol also interferes
with mitochondrial protein
synthesis in mammalian cell

4. Chloramphenicol- Antimicrobial Spectrum
Cidal activity Against Static activity against
H. Influenzae
N. Meningitides
S. Pneumoniae
Brucella spp.
Bordetella pertussis
Clostridium
Bacteroides
Mycoplasma
Chlamydia
Ricketssia
Proteus mirabilis & indole +ve proteus spp.
V. cholerae

5. Chloramphenicol- Mechanism of
resistance
1. Plasmid mediated production of acetyltransferase
inactivation of drug.
2. Decreased permeability
3. Production of altered ribosomes.

6. Chloramphenicol- Pharmacokinetics
Absorption:
◦Well and rapidly absorbed orally
◦Tmax (oral)= 2-3 hrs.
Chloramphenicol succinate is used for parenteral
purpose.
Distribution:
◦Widely distributed throughout the body including CSF (60%
of plasma conc.)

7. Chloramphenicol- Pharmacokinetics
Metabolism:
◦Hepatic metabolism to inactive glucuronides (major).
Excretion:
◦Metabolites & chloramphenicol itself are excreted in urine.

8. Chloramphenicol- Therapeutic Uses
General Points:
◦ Therapy with chloramphenicol must be limited to infections for
which the benefits of the drug outweigh the risks of the
potential toxicities.
◦ When other antimicrobial drugs that are equally effective and
potentially less toxic are available, they should be used instead
of chloramphenicol.

9. Chloramphenicol- Therapeutic Uses
1. Typhoid fever:
◦ NOT PREFERRED
◦ 1 g every 6 hours for 4 weeks.
2. Bacterial Meningitis
◦ patients who have severe allergy to beta-lactams.
◦ 50mg/kg/d in four divided doses for children.
3. Rickettsial Diseases:
◦ Patients allergic to tetracycline, pregnant women & children <8 years of age
requiring prolong therapy.
◦ Rocky Mountain spotted fever, epidemic, murine, scrub, and recrudescent typhus,
and Q fever.
◦ 50mg/kg/d in four divided doses. Dose may be doubled in case of resistance.

10. Chloramphenicol- Adverse Drug reactions
1. Hypersensitivity reactions
2. Haematological toxicities
◦ Dose related: anaemia, leukopenia or thrombocytopenia.
◦ Idiosyncratic: Aplastic anaemia resulting in fatal pancytopenia.
3. Other toxic & irritative effects
◦ Nausea, vomiting, unpleasant taste, diarrhoea & perineal irritation.
◦ Encephalopathy
◦ Cardiomyopathy
◦ Gray baby syndrome:
◦ Occurs in neonates (esp. premature). Vomiting, refusal to suck, irregular & rapid respiration,
abdominal distention, periods of cyanosis and passage of loose green stool. Over next 24 hours
babies may turn ashen grey & become flaccid and hypothermic.