Chloramphenicol is a broad-spectrum bacteriostatic and bactericidal antibiotic. It inhibits bacterial protein synthesis by binding reversibly to the 50S subunit of the bacterial ribosome, inhibiting peptidyl transferase and preventing the transfer of elongating peptide chains. While effective against a variety of bacteria, it can cause serious and sometimes fatal side effects like bone marrow suppression and gray baby syndrome in neonates due to immature drug metabolism pathways. As a result, it is now rarely used due to toxicity concerns and the availability of alternative antibiotics.

1. Chloramphenicol

2. introduction Broad spectrum (aerobic, anaerobic, gram +, gram -, rickettsiae) Bacteriostatic

3. Bactericidal (H.influenzae, Neisseria meningitidis)Step 1 – AA binds to AStep 2 – transpeptidation XProtein synthesis 50S30SPAStep 4 –translocation Step 3 – tRNA leaves P site

4. Inhibits protein synthesis Binds reversibly to 50S; Inhibits peptidyl transferaseXProtein synthesis XPA30SInhibits transfer of elongating peptide chain to newly attached aminoacyl tRNA at A site

5. Pharmacokinetics Chloramphenicol palmitate (oral)Chloramphenicol succinate (Parenteral) through oral route – completely & rapidly absorbedDose : 50 - 100 mg/kg/day Wide tissue distribution ( body fluids, CSF )Inactivated by glucuronide conjugationEliminated in urine, bile, feces

6. 1-10µg/ml - inhibits Gram +ve bacteria O.2-5µg/ml - inhibits Gram -ve bacteriaResistance due to chloramphenicol acetyl transferasedecreased permeability into bacterial cellsCross resistance seen between Chloramphenicol, Macrolides, Lincosamide

7. Clinical uses Typhoid

8. Typhus

9. Rocky Mountain Spotted Fever

10. Meningococcal meningitis

11. Topically for eye infections When chloramphenicol should not be prescribed ? hepatic failure new borns (<1wk) premature infants

12. Adverse effectsNausea, vomiting, diarrhoea, oral/vaginal candidiasisBone marrow disturbances: dose related reversible suppression of RBCs

13. aplastic anemia (idiosyncratic), irreversible, prolonged useGray Baby Syndrome

14. Gray baby syndrome stops feeding VomitingHypotonicHypothermic Distended abdomenIrregular respirationAshen gray cyanosis Cardiovascular collapse Death

15. Why Gray baby syndrome occurs in neonates ?Inability of neonate to metabolise & excrete chloramphenicol due to deficiency of glucuronosyl transferaseAt higher concentration it inhibits electron transport in liver, heart, skeletal muscle